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run_test_pred.sh can't run on CPU #8

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michaelanekson opened this issue Jul 4, 2024 · 8 comments
Closed

run_test_pred.sh can't run on CPU #8

michaelanekson opened this issue Jul 4, 2024 · 8 comments

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@michaelanekson
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Hello, I am trying to run your code for "predicting new data" part. I follow all your command from creating new environment, install the requirement based on your txt file, until running the bash script. However, when I ran the bash script, I get this issue:

(biorex) [michaela95@BLOOM BioREx]$ bash scripts/run_biorex_new.sh
Converting the dataset into BioREx input format
2024-07-04 14:00:33.031276: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:479] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered
2024-07-04 14:00:33.054684: E external/local_xla/xla/stream_executor/cuda/cuda_dnn.cc:10575] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered
2024-07-04 14:00:33.054743: E external/local_xla/xla/stream_executor/cuda/cuda_blas.cc:1442] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered
2024-07-04 14:00:33.071248: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations.
To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags.
2024-07-04 14:00:34.221688: W tensorflow/compiler/tf2tensorrt/utils/py_utils.cc:38] TF-TRT Warning: Could not find TensorRT
number_unique_YES_instances 0
Generating RE predictions
2024-07-04 14:00:38.500149: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:479] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered
2024-07-04 14:00:38.524087: E external/local_xla/xla/stream_executor/cuda/cuda_dnn.cc:10575] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered
2024-07-04 14:00:38.524137: E external/local_xla/xla/stream_executor/cuda/cuda_blas.cc:1442] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered
2024-07-04 14:00:38.540547: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations.
To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags.
2024-07-04 14:00:39.539068: W tensorflow/compiler/tf2tensorrt/utils/py_utils.cc:38] TF-TRT Warning: Could not find TensorRT
[INFO|training_args.py:804] 2024-07-04 14:00:42,112 >> using logging_steps to initialize eval_steps to 10
[INFO|training_args.py:1023] 2024-07-04 14:00:42,112 >> PyTorch: setting up devices
[INFO|training_args.py:885] 2024-07-04 14:00:42,113 >> The default value for the training argument --report_to will change in v5 (from all installed integrations to none). In v5, you will need to use --report_to all to get the same behavior as now. You should start updating your code and make this info disappear :-).
[INFO|training_args_tf.py:189] 2024-07-04 14:00:42,114 >> Tensorflow: setting up strategy
07/04/2024 14:00:42 - INFO - main - n_replicas: 1, distributed training: False, 16-bits training: False
07/04/2024 14:00:42 - INFO - main - Training/evaluation parameters TFTrainingArguments(
_n_gpu=0,
adafactor=False,
adam_beta1=0.9,
adam_beta2=0.999,
adam_epsilon=1e-08,
bf16=False,
bf16_full_eval=False,
data_seed=None,
dataloader_drop_last=False,
dataloader_num_workers=0,
dataloader_pin_memory=True,
ddp_bucket_cap_mb=None,
ddp_find_unused_parameters=None,
debug=[],
deepspeed=None,
disable_tqdm=False,
do_eval=True,
do_predict=True,
do_train=False,
eval_accumulation_steps=None,
eval_delay=0,
eval_steps=10,
evaluation_strategy=IntervalStrategy.STEPS,
fp16=False,
fp16_backend=auto,
fp16_full_eval=False,
fp16_opt_level=O1,
gcp_project=None,
gradient_accumulation_steps=1,
gradient_checkpointing=False,
greater_is_better=None,
group_by_length=False,
half_precision_backend=auto,
hub_model_id=None,
hub_strategy=HubStrategy.EVERY_SAVE,
hub_token=<HUB_TOKEN>,
ignore_data_skip=False,
label_names=None,
label_smoothing_factor=0.0,
learning_rate=5e-05,
length_column_name=length,
load_best_model_at_end=False,
local_rank=-1,
log_level=-1,
log_level_replica=-1,
log_on_each_node=True,
logging_dir=biorex_model/runs/Jul04_14-00-42_BLOOM,
logging_first_step=False,
logging_nan_inf_filter=True,
logging_steps=10,
logging_strategy=IntervalStrategy.STEPS,
lr_scheduler_type=SchedulerType.LINEAR,
max_grad_norm=1.0,
max_steps=-1,
metric_for_best_model=None,
mp_parameters=,
no_cuda=False,
num_train_epochs=10.0,
optim=OptimizerNames.ADAMW_HF,
output_dir=biorex_model,
overwrite_output_dir=True,
past_index=-1,
per_device_eval_batch_size=32,
per_device_train_batch_size=16,
poly_power=1.0,
prediction_loss_only=False,
push_to_hub=False,
push_to_hub_model_id=None,
push_to_hub_organization=None,
push_to_hub_token=<PUSH_TO_HUB_TOKEN>,
remove_unused_columns=True,
report_to=['tensorboard'],
resume_from_checkpoint=None,
run_name=biorex_model,
save_on_each_node=False,
save_steps=10,
save_strategy=IntervalStrategy.STEPS,
save_total_limit=None,
seed=42,
sharded_ddp=[],
skip_memory_metrics=True,
tf32=None,
tpu_metrics_debug=False,
tpu_name=None,
tpu_num_cores=None,
tpu_zone=None,
use_legacy_prediction_loop=False,
warmup_ratio=0.0,
warmup_steps=0,
weight_decay=0.0,
xla=False,
xpu_backend=None,
)
[INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/vocab.txt
[INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/tokenizer.json
[INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/added_tokens.json
[INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/special_tokens_map.json
[INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/tokenizer_config.json
=======================>label2id {'None': 0, 'Association': 1, 'Bind': 2, 'Comparison': 3, 'Conversion': 4, 'Cotreatment': 5, 'Drug_Interaction': 6, 'Negative_Correlation': 7, 'Positive_Correlation': 8, 'None-CID': 9, 'CID': 10, 'None-PPIm': 11, 'PPIm': 12, 'None-AIMED': 13, 'None-DDI': 14, 'None-BC7': 15, 'None-phargkb': 16, 'None-GDA': 17, 'None-DISGENET': 18, 'None-EMU_BC': 19, 'None-EMU_PC': 20, 'None-HPRD50': 21, 'None-PHARMGKB': 22, 'ACTIVATOR': 23, 'AGONIST': 24, 'AGONIST-ACTIVATOR': 25, 'AGONIST-INHIBITOR': 26, 'ANTAGONIST': 27, 'DIRECT-REGULATOR': 28, 'INDIRECT-DOWNREGULATOR': 29, 'INDIRECT-UPREGULATOR': 30, 'INHIBITOR': 31, 'PART-OF': 32, 'PRODUCT-OF': 33, 'SUBSTRATE': 34, 'SUBSTRATE_PRODUCT-OF': 35, 'mechanism': 36, 'int': 37, 'effect': 38, 'advise': 39, 'AIMED-Association': 40, 'HPRD-Association': 41, 'EUADR-Association': 42, 'None-EUADR': 43, 'Indirect_conversion': 44, 'Non_conversion': 45}
=======================>positive_label
=======================>use_balanced_neg False
=======================>max_neg_scale 2
07/04/2024 14:00:42 - INFO - main - pos_label_ids
07/04/2024 14:00:42 - INFO - main - [1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 17, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45]
[INFO|configuration_utils.py:652] 2024-07-04 14:00:42,153 >> loading configuration file pretrained_model/config.json
[INFO|configuration_utils.py:690] 2024-07-04 14:00:42,154 >> Model config BertConfig {
"_name_or_path": "pretrained_model",
"architectures": [
"BertForSequenceClassification"
],
"attention_probs_dropout_prob": 0.1,
"classifier_dropout": null,
"finetuning_task": "text-classification",
"hidden_act": "gelu",
"hidden_dropout_prob": 0.1,
"hidden_size": 768,
"id2label": {
"0": "None",
"1": "Association",
"2": "Bind",
"3": "Comparison",
"4": "Conversion",
"5": "Cotreatment",
"6": "Drug_Interaction",
"7": "Negative_Correlation",
"8": "Positive_Correlation",
"9": "None-CID",
"10": "CID",
"11": "None-PPIm",
"12": "PPIm",
"13": "None-AIMED",
"14": "None-DDI",
"15": "None-BC7",
"16": "None-phargkb",
"17": "None-GDA",
"18": "None-DISGENET",
"19": "None-EMU_BC",
"20": "None-EMU_PC",
"21": "None-HPRD50",
"22": "None-PHARMGKB",
"23": "ACTIVATOR",
"24": "AGONIST",
"25": "AGONIST-ACTIVATOR",
"26": "AGONIST-INHIBITOR",
"27": "ANTAGONIST",
"28": "DIRECT-REGULATOR",
"29": "INDIRECT-DOWNREGULATOR",
"30": "INDIRECT-UPREGULATOR",
"31": "INHIBITOR",
"32": "PART-OF",
"33": "PRODUCT-OF",
"34": "SUBSTRATE",
"35": "SUBSTRATE_PRODUCT-OF",
"36": "mechanism",
"37": "int",
"38": "effect",
"39": "advise",
"40": "AIMED-Association",
"41": "HPRD-Association",
"42": "EUADR-Association",
"43": "None-EUADR",
"44": "Indirect_conversion",
"45": "Non_conversion"
},
"initializer_range": 0.02,
"intermediate_size": 3072,
"label2id": {
"ACTIVATOR": 23,
"AGONIST": 24,
"AGONIST-ACTIVATOR": 25,
"AGONIST-INHIBITOR": 26,
"AIMED-Association": 40,
"ANTAGONIST": 27,
"Association": 1,
"Bind": 2,
"CID": 10,
"Comparison": 3,
"Conversion": 4,
"Cotreatment": 5,
"DIRECT-REGULATOR": 28,
"Drug_Interaction": 6,
"EUADR-Association": 42,
"HPRD-Association": 41,
"INDIRECT-DOWNREGULATOR": 29,
"INDIRECT-UPREGULATOR": 30,
"INHIBITOR": 31,
"Indirect_conversion": 44,
"Negative_Correlation": 7,
"Non_conversion": 45,
"None": 0,
"None-AIMED": 13,
"None-BC7": 15,
"None-CID": 9,
"None-DDI": 14,
"None-DISGENET": 18,
"None-EMU_BC": 19,
"None-EMU_PC": 20,
"None-EUADR": 43,
"None-GDA": 17,
"None-HPRD50": 21,
"None-PHARMGKB": 22,
"None-PPIm": 11,
"None-phargkb": 16,
"PART-OF": 32,
"PPIm": 12,
"PRODUCT-OF": 33,
"Positive_Correlation": 8,
"SUBSTRATE": 34,
"SUBSTRATE_PRODUCT-OF": 35,
"advise": 39,
"effect": 38,
"int": 37,
"mechanism": 36
},
"layer_norm_eps": 1e-12,
"max_position_embeddings": 512,
"model_type": "bert",
"num_attention_heads": 12,
"num_hidden_layers": 12,
"pad_token_id": 0,
"position_embedding_type": "absolute",
"transformers_version": "4.18.0",
"type_vocab_size": 2,
"use_cache": true,
"vocab_size": 28933
}

[INFO|modeling_tf_utils.py:1776] 2024-07-04 14:00:42,177 >> loading weights file pretrained_model/tf_model.h5
/media/data/biorex/lib/python3.10/site-packages/keras/src/layers/layer.py:1331: UserWarning: Layer 'tf_bert_for_sequence_classification' looks like it has unbuilt state, but Keras is not able to trace the layer call() in order to build it automatically. Possible causes:

  1. The call() method of your layer may be crashing. Try to __call__() the layer eagerly on some test input first to see if it works. E.g. x = np.random.random((3, 4)); y = layer(x)
  2. If the call() method is correct, then you may need to implement the def build(self, input_shape) method on your layer. It should create all variables used by the layer (e.g. by calling layer.build() on all its children layers).
    Exception encountered: ''Exception encountered when calling TFBertMainLayer.call().

'NoneType' object has no attribute 'shape'

Arguments received by TFBertMainLayer.call():
• input_ids=tf.Tensor(shape=(3, 5), dtype=int32)
• attention_mask=None
• token_type_ids=None
• position_ids=None
• head_mask=None
• inputs_embeds=None
• encoder_hidden_states=None
• encoder_attention_mask=None
• past_key_values=None
• use_cache=None
• output_attentions=False
• output_hidden_states=False
• return_dict=True
• training=False''
warnings.warn(
/media/data/biorex/lib/python3.10/site-packages/keras/src/layers/layer.py:372: UserWarning: build() was called on layer 'tf_bert_for_sequence_classification', however the layer does not have a build() method implemented and it looks like it has unbuilt state. This will cause the layer to be marked as built, despite not being actually built, which may cause failures down the line. Make sure to implement a proper build() method.
warnings.warn(
Traceback (most recent call last):
File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/run_ncbi_rel_exp.py", line 884, in
main()
File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/run_ncbi_rel_exp.py", line 687, in main
model = TFAutoModelForSequenceClassification.from_pretrained(
File "/media/data/biorex/lib/python3.10/site-packages/transformers/models/auto/auto_factory.py", line 446, in from_pretrained
return model_class.from_pretrained(pretrained_model_name_or_path, *model_args, config=config, **kwargs)
File "/media/data/biorex/lib/python3.10/site-packages/transformers/modeling_tf_utils.py", line 1803, in from_pretrained
model(model.dummy_inputs) # build the network with dummy inputs
File "/media/data/biorex/lib/python3.10/site-packages/keras/src/utils/traceback_utils.py", line 122, in error_handler
raise e.with_traceback(filtered_tb) from None
File "/media/data/biorex/lib/python3.10/site-packages/transformers/modeling_tf_utils.py", line 383, in run_call_with_unpacked_inputs
return func(self, **unpacked_inputs)
File "/media/data/biorex/lib/python3.10/site-packages/transformers/models/bert/modeling_tf_bert.py", line 1633, in call
outputs = self.bert(
File "/media/data/biorex/lib/python3.10/site-packages/transformers/modeling_tf_utils.py", line 383, in run_call_with_unpacked_inputs
return func(self, **unpacked_inputs)
File "/media/data/biorex/lib/python3.10/site-packages/transformers/models/bert/modeling_tf_bert.py", line 850, in call
encoder_outputs = self.encoder(
File "/media/data/biorex/lib/python3.10/site-packages/optree/ops.py", line 594, in tree_map
return treespec.unflatten(map(func, *flat_args))
AttributeError: Exception encountered when calling TFBertMainLayer.call().

'NoneType' object has no attribute 'shape'

Arguments received by TFBertMainLayer.call():
• input_ids=tf.Tensor(shape=(3, 5), dtype=int32)
• attention_mask=None
• token_type_ids=None
• position_ids=None
• head_mask=None
• inputs_embeds=None
• encoder_hidden_states=None
• encoder_attention_mask=None
• past_key_values=None
• use_cache=None
• output_attentions=False
• output_hidden_states=False
• return_dict=True
• training=False
cp: cannot stat 'biorex_model/test_results.tsv': No such file or directory
2024-07-04 14:00:46.035576: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:479] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered
2024-07-04 14:00:46.059361: E external/local_xla/xla/stream_executor/cuda/cuda_dnn.cc:10575] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered
2024-07-04 14:00:46.059424: E external/local_xla/xla/stream_executor/cuda/cuda_blas.cc:1442] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered
2024-07-04 14:00:46.075918: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations.
To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags.
2024-07-04 14:00:47.150909: W tensorflow/compiler/tf2tensorrt/utils/py_utils.cc:38] TF-TRT Warning: Could not find TensorRT
Traceback (most recent call last):
File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/utils/run_pubtator_eval.py", line 1557, in
dump_pred_2_pubtator_file(in_pubtator_file = in_test_pubtator_file,
File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/utils/run_pubtator_eval.py", line 206, in dump_pred_2_pubtator_file
add_relation_pairs_dict(
File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/utils/run_pubtator_eval.py", line 83, in add_relation_pairs_dict
testdf = pd.read_csv(in_gold_tsv_file, sep="\t", index_col=0)
File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 1026, in read_csv
return _read(filepath_or_buffer, kwds)
File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 620, in _read
parser = TextFileReader(filepath_or_buffer, **kwds)
File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 1620, in init
self._engine = self._make_engine(f, self.engine)
File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 1898, in _make_engine
return mapping[engine](f, **self.options)
File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/c_parser_wrapper.py", line 93, in init
self._reader = parsers.TextReader(src, **kwds)
File "parsers.pyx", line 581, in pandas._libs.parsers.TextReader.cinit
pandas.errors.EmptyDataError: No columns to parse from file

Would you tell what should I do in dealing with this situation?

@ptlai
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ptlai commented Jul 9, 2024

Hi @michaelanekson,

Here's a more native and fluent version of the message: Hi Michael, Thanks for bringing this error to our attention. It could be due to either an environment issue or a problem with the input PubTator file.

I've updated the requirements.txt to address potential environment-related issues.

As for the input file, would you mind sharing yours with me? Alternatively, you could try using the bc8_biored_task1_val.pubtator file from the BC8-BioRED dataset. You can find it in this ZIP archive: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/BC8_BioRED_Subtask1_PubTator.zip. Give it a shot and see if the program runs without errors.

Let me know if you need any further assistance!

Best,
Po-Ting

@michaelanekson
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Author

michaelanekson commented Jul 9, 2024

Here my input file, you can download it. Actually, my input file is already PubTator file but I don't why It doesn't work. You can see it in my uploaded file.
I already see your file BioRED and the format is Pubtator as same as mine.

sample.zip

Recently, I solve the problem by loading your LLM model manually using transformers. The situation is I am trying to load Pubtator3 BioLinkBERT and it works for me. Would you see my modified LLM code? maybe you can correct me if I use your LLM model in the wrong way.
modified BioREx code.zip

One more thing about environmental issue, I think if we use the most updated transformers, tensorflow, or biospacy, it does not work properly. So, I agree with your current modified requirement

@ptlai
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ptlai commented Jul 10, 2024

Hi @michaelanekson,

Thank you for sharing the files. I've taken a look at your sample file, and I noticed you're using PubTator NE types instead of BioRED NE types. If you've downloaded your sample file from PubTator, you can use the converter mentioned in this GitHub issue comment to convert it to BioRED NE types.

Since the NE type tags are different, it might negatively impact the script you provided. I'd recommend using our leaderboard's dataset and evaluation to test it before applying it to your own dataset.

Also, if you're only interested in results for PubMed abstracts, we've already processed the entire PubMed database. You can find that data here.

@michaelanekson
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Hello, I already try with your BioRED dataset and it works in annotation part but it is not working in relation extraction part. The model that I use is pretrained_model_biolinkbert. Here's the error description:
2024-07-11 15:23:21,367 - INFO - Annotation: pain, Type: DiseaseOrPhenotypicFeature, Position: 91
2024-07-11 15:23:21,367 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 169
2024-07-11 15:23:21,367 - INFO - Annotation: neurocognitive decline, Type: DiseaseOrPhenotypicFeature, Position: 202
2024-07-11 15:23:21,368 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 426
2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 539
2024-07-11 15:23:21,368 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 557
2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 792
2024-07-11 15:23:21,368 - INFO - Annotation: human, Type: OrganismTaxon, Position: 812
2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 868
2024-07-11 15:23:21,368 - INFO - Annotation: heterogeneous nuclear ribonucleoprotein complex A2/B1, Type: GeneOrGeneProduct, Position: 1032
2024-07-11 15:23:21,368 - INFO - Annotation: hnRNP A2/B1, Type: GeneOrGeneProduct, Position: 1087
2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1114
2024-07-11 15:23:21,368 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1160
2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1200
2024-07-11 15:23:21,368 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1261
2024-07-11 15:23:21,369 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1272
2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1350
2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1455
2024-07-11 15:23:21,369 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1477
2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1500
2024-07-11 15:23:21,369 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1527
2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1535
2024-07-11 15:23:21,369 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1570
2024-07-11 15:23:21,369 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1673
2024-07-11 15:23:21,369 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 1695
2024-07-11 15:23:21,369 - INFO - Annotation: CD31, Type: GeneOrGeneProduct, Position: 1759
2024-07-11 15:23:21,369 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 1821
2024-07-11 15:23:21,370 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1968
2024-07-11 15:23:21,370 - INFO - Annotation: NG2, Type: GeneOrGeneProduct, Position: 2007
2024-07-11 15:23:21,370 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 2017
2024-07-11 15:23:21,370 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 2043
2024-07-11 15:23:21,370 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 2086
2024-07-11 15:23:21,370 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 2258
2024-07-11 15:23:21,370 - INFO - Document ID: BC8_BioRED_Task1_Doc1482
2024-07-11 15:23:21,370 - INFO - Text Instance: Fine mapping and identification of a candidate gene SSH1 in disseminated superficial actinic porokeratosis.
2024-07-11 15:23:21,370 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 52
2024-07-11 15:23:21,370 - INFO - Annotation: disseminated superficial actinic porokeratosis, Type: DiseaseOrPhenotypicFeature, Position: 60
2024-07-11 15:23:21,370 - INFO - Text Instance: Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP.
2024-07-11 15:23:21,371 - INFO - Annotation: Disseminated superficial actinic porokeratosis, Type: DiseaseOrPhenotypicFeature, Position: 0
2024-07-11 15:23:21,371 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 48
2024-07-11 15:23:21,371 - INFO - Annotation: keratinization disorder, Type: DiseaseOrPhenotypicFeature, Position: 96
2024-07-11 15:23:21,371 - INFO - Annotation: keratotic lesions, Type: DiseaseOrPhenotypicFeature, Position: 159
2024-07-11 15:23:21,371 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 259
2024-07-11 15:23:21,371 - INFO - Annotation: p.Ser63Asn, Type: GeneOrGeneProduct, Position: 626
2024-07-11 15:23:21,371 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 640
2024-07-11 15:23:21,371 - INFO - Annotation: p.Ser19CysfsX24, Type: GeneOrGeneProduct, Position: 683
2024-07-11 15:23:21,371 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 740
2024-07-11 15:23:21,371 - INFO - Annotation: p.Pro27ProfsX54, Type: GeneOrGeneProduct, Position: 791
2024-07-11 15:23:21,371 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 869
2024-07-11 15:23:21,371 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 875
2024-07-11 15:23:21,372 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 1065
2024-07-11 15:23:21,372 - INFO - Document ID: BC8_BioRED_Task1_Doc1483
2024-07-11 15:23:21,372 - INFO - Text Instance: Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: frequency distribution in a healthy German population.
2024-07-11 15:23:21,372 - INFO - Annotation: venous and arterial thromboembolism, Type: DiseaseOrPhenotypicFeature, Position: 63
2024-07-11 15:23:21,372 - INFO - Text Instance: Evolvement and progression of cardiovascular diseases affecting the venous and arterial system are influenced by a multitude of environmental and hereditary factors. Many of these hereditary factors consist of defined gene polymorphisms, such as single nucleotide polymorphisms (SNPs) or insertion-deletion polymorphisms, which directly or indirectly affect the hemostatic system. The frequencies of individual hemostatic gene polymorphisms in different normal populations are well defined. However, descriptions of patterns of genetic variability of a larger extent of different factors of hereditary hypercoagulability in single populations are scarce. The aim of this study was i) to give a detailed description of the frequencies of factors of hereditary thrombophilia and their combinations in a German population (n = 282) and ii) to compare their distributions with those reported for other regions. Variants of coagulation factors [factor V 1691G>A (factor V Leiden), factor V 4070A>G (factor V HR2 haplotype), factor VII Arg353Gln, factor XIII Val34Leu, beta-fibrinogen -455G>A, prothrombin 20210G>A], coagulation inhibitors [tissue factor pathway inhibitor 536C>T, thrombomodulin 127G>A], fibrinolytic factors [angiotensin converting enzyme intron 16 insertion/deletion, factor VII-activating protease 1601G>A (FSAP Marburg I), plasminogen activator inhibitor 1-675 insertion/deletion (5G/4G), tissue plasminogen activator intron h deletion/insertion], and other factors implicated in influencing susceptibility to thromboembolic diseases [apolipoprotein E2/E3/E4, glycoprotein Ia 807C>T, methylenetetrahydrofolate reductase 677C>T] were included. The distribution of glycoprotein Ia 807C>T deviated significantly from the Hardy-Weinberg equilibrium, and a comparison with previously published data indicates marked region and ethnicity dependent differences in the genotype distributions of some other factors.
2024-07-11 15:23:21,372 - INFO - Annotation: cardiovascular diseases, Type: DiseaseOrPhenotypicFeature, Position: 30
2024-07-11 15:23:21,372 - INFO - Annotation: hereditary hypercoagulability, Type: DiseaseOrPhenotypicFeature, Position: 591
2024-07-11 15:23:21,372 - INFO - Annotation: hereditary thrombophilia, Type: DiseaseOrPhenotypicFeature, Position: 748
2024-07-11 15:23:21,372 - INFO - Annotation: factor V, Type: GeneOrGeneProduct, Position: 940
2024-07-11 15:23:21,372 - INFO - Annotation: 1691G>A, Type: GeneOrGeneProduct, Position: 949
2024-07-11 15:23:21,372 - INFO - Annotation: factor V Leiden, Type: GeneOrGeneProduct, Position: 958
2024-07-11 15:23:21,373 - INFO - Annotation: factor V, Type: GeneOrGeneProduct, Position: 976
2024-07-11 15:23:21,373 - INFO - Annotation: 4070A>G, Type: GeneOrGeneProduct, Position: 985
2024-07-11 15:23:21,373 - INFO - Annotation: factor V, Type: GeneOrGeneProduct, Position: 994
2024-07-11 15:23:21,373 - INFO - Annotation: factor VII, Type: GeneOrGeneProduct, Position: 1019
2024-07-11 15:23:21,373 - INFO - Annotation: Arg353Gln, Type: GeneOrGeneProduct, Position: 1030
2024-07-11 15:23:21,373 - INFO - Annotation: factor XIII, Type: GeneOrGeneProduct, Position: 1041
2024-07-11 15:23:21,373 - INFO - Annotation: Val34Leu, Type: GeneOrGeneProduct, Position: 1053
2024-07-11 15:23:21,373 - INFO - Annotation: beta-fibrinogen, Type: GeneOrGeneProduct, Position: 1063
2024-07-11 15:23:21,373 - INFO - Annotation: -455G>A, Type: GeneOrGeneProduct, Position: 1079
2024-07-11 15:23:21,373 - INFO - Annotation: prothrombin, Type: GeneOrGeneProduct, Position: 1088
2024-07-11 15:23:21,373 - INFO - Annotation: 20210G>A, Type: GeneOrGeneProduct, Position: 1100
2024-07-11 15:23:21,373 - INFO - Annotation: tissue factor pathway inhibitor, Type: GeneOrGeneProduct, Position: 1135
2024-07-11 15:23:21,374 - INFO - Annotation: 536C>T, Type: GeneOrGeneProduct, Position: 1167
2024-07-11 15:23:21,374 - INFO - Annotation: thrombomodulin, Type: GeneOrGeneProduct, Position: 1175
2024-07-11 15:23:21,374 - INFO - Annotation: 127G>A, Type: GeneOrGeneProduct, Position: 1190
2024-07-11 15:23:21,374 - INFO - Annotation: angiotensin converting enzyme, Type: GeneOrGeneProduct, Position: 1221
2024-07-11 15:23:21,374 - INFO - Annotation: factor VII-activating protease, Type: GeneOrGeneProduct, Position: 1281
2024-07-11 15:23:21,374 - INFO - Annotation: 1601G>A, Type: GeneOrGeneProduct, Position: 1312
2024-07-11 15:23:21,374 - INFO - Annotation: FSAP, Type: GeneOrGeneProduct, Position: 1321
2024-07-11 15:23:21,374 - INFO - Annotation: plasminogen activator inhibitor 1, Type: GeneOrGeneProduct, Position: 1338
2024-07-11 15:23:21,374 - INFO - Annotation: 675 insertion/deletion, Type: GeneOrGeneProduct, Position: 1372
2024-07-11 15:23:21,374 - INFO - Annotation: tissue plasminogen activator, Type: GeneOrGeneProduct, Position: 1404
2024-07-11 15:23:21,374 - INFO - Annotation: thromboembolic diseases, Type: DiseaseOrPhenotypicFeature, Position: 1525
2024-07-11 15:23:21,375 - INFO - Annotation: apolipoprotein E2/E3/E4, glycoprotein Ia, Type: GeneOrGeneProduct, Position: 1550
2024-07-11 15:23:21,375 - INFO - Annotation: 807C>T, Type: GeneOrGeneProduct, Position: 1591
2024-07-11 15:23:21,375 - INFO - Annotation: methylenetetrahydrofolate reductase, Type: GeneOrGeneProduct, Position: 1599
2024-07-11 15:23:21,375 - INFO - Annotation: 677C>T, Type: GeneOrGeneProduct, Position: 1635
2024-07-11 15:23:21,375 - INFO - Annotation: glycoprotein Ia, Type: GeneOrGeneProduct, Position: 1678
2024-07-11 15:23:21,375 - INFO - Annotation: 807C>T, Type: GeneOrGeneProduct, Position: 1694
2024-07-11 15:23:21,375 - INFO - Document ID: BC8_BioRED_Task1_Doc1484
2024-07-11 15:23:21,375 - INFO - Text Instance: Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome.
2024-07-11 15:23:21,375 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 26
2024-07-11 15:23:21,375 - INFO - Annotation: Marfan syndrome, Type: DiseaseOrPhenotypicFeature, Position: 70
2024-07-11 15:23:21,375 - INFO - Text Instance: PURPOSE: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS). METHODS: Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation. RESULTS: A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 (p.S1235P). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain. CONCLUSIONS: We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome.
2024-07-11 15:23:21,375 - INFO - Annotation: fibrillin-1, Type: GeneOrGeneProduct, Position: 41
2024-07-11 15:23:21,375 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 59
2024-07-11 15:23:21,375 - INFO - Annotation: Marfan syndrome, Type: DiseaseOrPhenotypicFeature, Position: 90
2024-07-11 15:23:21,375 - INFO - Annotation: MFS, Type: DiseaseOrPhenotypicFeature, Position: 107
2024-07-11 15:23:21,376 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 122
2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 422
2024-07-11 15:23:21,376 - INFO - Annotation: c.3703T>C, Type: GeneOrGeneProduct, Position: 931
2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 962
2024-07-11 15:23:21,376 - INFO - Annotation: serine by proline at codon 1235, Type: GeneOrGeneProduct, Position: 1034
2024-07-11 15:23:21,376 - INFO - Annotation: p.S1235P, Type: GeneOrGeneProduct, Position: 1067
2024-07-11 15:23:21,376 - INFO - Annotation: calcium, Type: ChemicalEntity, Position: 1257
2024-07-11 15:23:21,376 - INFO - Annotation: epidermal growth factor, Type: GeneOrGeneProduct, Position: 1273
2024-07-11 15:23:21,376 - INFO - Annotation: p.S1235P, Type: GeneOrGeneProduct, Position: 1453
2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 1474
2024-07-11 15:23:21,376 - INFO - Annotation: MFS, Type: DiseaseOrPhenotypicFeature, Position: 1516
2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 1580
2024-07-11 15:23:21,376 - INFO - Annotation: Marfan syndrome, Type: DiseaseOrPhenotypicFeature, Position: 1647
2024-07-11 15:23:21,376 - INFO - Document ID: BC8_BioRED_Task1_Doc1485
2024-07-11 15:23:21,377 - INFO - Text Instance: Evaluation of Ascorbic Acid Niosomes as Potential Detoxifiers in Oxidative Stress-induced HEK-293 Cells by Arsenic Trioxide.
2024-07-11 15:23:21,377 - INFO - Annotation: Ascorbic Acid, Type: ChemicalEntity, Position: 14
2024-07-11 15:23:21,377 - INFO - Annotation: as, Type: ChemicalEntity, Position: 37
2024-07-11 15:23:21,377 - INFO - Annotation: HEK-293, Type: CellLine, Position: 90
2024-07-11 15:23:21,377 - INFO - Annotation: Arsenic Trioxide, Type: ChemicalEntity, Position: 107
2024-07-11 15:23:21,377 - INFO - Text Instance: Background: As an environmental contaminant, Arsenic (As) poses many risks to human health. Increased Oxidative Stress (OS) and decreased antioxidant cell defense are the suggested mechanisms of carcinogenicity and toxicity of As. As a powerful antioxidant and water-soluble compound, vitamin C protects cells and tissues against oxidation and has a wide range of healing properties. Objectives: The current study aimed to formulate a suitable ascorbic acid (vitamin C) niosome and compare it with vitamin C in preventing As-induced toxicity in HEK-293 cells. Methods: Various formulas of vitamin C niosomes were prepared by C-SPAN mixed with cholesterol. The physicochemical characteristics of niosomal formulations, including load size, zeta-potential, and the drug release profile, were evaluated in HEK-293 cells. Then, OS biomarkers such as total reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), Antioxidant Capacity (TAC), and superoxide dismutase (SOD) activities determined the protective effects of vitamin C niosomes compared with vitamin C against As-induced toxicity. Results: The particle size and zeta potential of the optimal vitamin C niosome were 163.2 +- 6.1 nm and 23.3 +- 3.5 mV, respectively. Arsenic increased ROS and MDA levels while decreasing CAT, TAC, and SOD activities in the HEK-293 cell line. Finally, the vitamin C niosome decreased OS and increased antioxidant properties more than vitamin C. Significance: Vitamin C niosome was more effective than vitamin C in treating As-induced toxicity in vitro.
2024-07-11 15:23:21,418 - INFO - Annotation: As, Type: ChemicalEntity, Position: 12
2024-07-11 15:23:21,418 - INFO - Annotation: Arsenic, Type: ChemicalEntity, Position: 45
2024-07-11 15:23:21,418 - INFO - Annotation: As, Type: ChemicalEntity, Position: 54
2024-07-11 15:23:21,418 - INFO - Annotation: human, Type: OrganismTaxon, Position: 78
2024-07-11 15:23:21,419 - INFO - Annotation: carcinogenicity, Type: DiseaseOrPhenotypicFeature, Position: 195
2024-07-11 15:23:21,419 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 215
2024-07-11 15:23:21,419 - INFO - Annotation: As, Type: ChemicalEntity, Position: 227
2024-07-11 15:23:21,419 - INFO - Annotation: As, Type: ChemicalEntity, Position: 231
2024-07-11 15:23:21,419 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 285
2024-07-11 15:23:21,419 - INFO - Annotation: ascorbic acid, Type: ChemicalEntity, Position: 444
2024-07-11 15:23:21,419 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 459
2024-07-11 15:23:21,419 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 498
2024-07-11 15:23:21,419 - INFO - Annotation: As, Type: ChemicalEntity, Position: 522
2024-07-11 15:23:21,419 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 533
2024-07-11 15:23:21,419 - INFO - Annotation: HEK-293, Type: CellLine, Position: 545
2024-07-11 15:23:21,420 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 589
2024-07-11 15:23:21,420 - INFO - Annotation: cholesterol, Type: ChemicalEntity, Position: 643
2024-07-11 15:23:21,420 - INFO - Annotation: HEK-293, Type: CellLine, Position: 803
2024-07-11 15:23:21,420 - INFO - Annotation: as, Type: ChemicalEntity, Position: 843
2024-07-11 15:23:21,420 - INFO - Annotation: reactive oxygen species, Type: ChemicalEntity, Position: 852
2024-07-11 15:23:21,420 - INFO - Annotation: ROS, Type: ChemicalEntity, Position: 877
2024-07-11 15:23:21,420 - INFO - Annotation: malondialdehyde, Type: ChemicalEntity, Position: 883
2024-07-11 15:23:21,420 - INFO - Annotation: MDA, Type: ChemicalEntity, Position: 900
2024-07-11 15:23:21,420 - INFO - Annotation: catalase, Type: GeneOrGeneProduct, Position: 906
2024-07-11 15:23:21,420 - INFO - Annotation: CAT, Type: GeneOrGeneProduct, Position: 916
2024-07-11 15:23:21,420 - INFO - Annotation: superoxide dismutase, Type: GeneOrGeneProduct, Position: 954
2024-07-11 15:23:21,420 - INFO - Annotation: SOD, Type: GeneOrGeneProduct, Position: 976
2024-07-11 15:23:21,421 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1029
2024-07-11 15:23:21,421 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1062
2024-07-11 15:23:21,421 - INFO - Annotation: As, Type: ChemicalEntity, Position: 1080
2024-07-11 15:23:21,421 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 1091
2024-07-11 15:23:21,421 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1162
2024-07-11 15:23:21,421 - INFO - Annotation: Arsenic, Type: ChemicalEntity, Position: 1235
2024-07-11 15:23:21,421 - INFO - Annotation: ROS, Type: ChemicalEntity, Position: 1253
2024-07-11 15:23:21,421 - INFO - Annotation: MDA, Type: ChemicalEntity, Position: 1261
2024-07-11 15:23:21,421 - INFO - Annotation: CAT, Type: GeneOrGeneProduct, Position: 1289
2024-07-11 15:23:21,421 - INFO - Annotation: SOD, Type: GeneOrGeneProduct, Position: 1303
2024-07-11 15:23:21,421 - INFO - Annotation: HEK-293, Type: CellLine, Position: 1325
2024-07-11 15:23:21,422 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1357
2024-07-11 15:23:21,422 - INFO - Annotation: vitamin C., Type: ChemicalEntity, Position: 1435
2024-07-11 15:23:21,422 - INFO - Annotation: Vitamin C, Type: ChemicalEntity, Position: 1460
2024-07-11 15:23:21,422 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1502
2024-07-11 15:23:21,422 - INFO - Annotation: As, Type: ChemicalEntity, Position: 1524
2024-07-11 15:23:21,422 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 1535
2024-07-11 15:23:21,422 - INFO - Document ID: BC8_BioRED_Task1_Doc1486
2024-07-11 15:23:21,422 - INFO - Text Instance: Tetrahydroindazole inhibitors of CDK2/cyclin complexes.
2024-07-11 15:23:21,422 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 33
2024-07-11 15:23:21,422 - INFO - Annotation: cyclin, Type: GeneOrGeneProduct, Position: 38
2024-07-11 15:23:21,422 - INFO - Text Instance: Over 50 tetrahydroindazoles were synthesized after 7-bromo-3,6,6-trimethyl-1-(pyridin-2-yl)-5,6,7,7a-tetrahydro-1H-indazol-4(3aH)-one (3) was identified as a hit compound in a high throughput screen for inhibition of CDK2 in complex with cyclin A. The activity of the most promising analogues was evaluated by inhibition of CDK2 enzyme complexes with various cyclins. Analogues 53 and 59 showed 3-fold better binding affinity for CDK2 and 2- to 10-fold improved inhibitory activity against CDK2/cyclin A1, E, and O compared to screening hit 3. The data from the enzyme and binding assays indicate that the binding of the analogues to a CDK2/cyclin complex is favored over binding to free CDK2. Computational analysis was used to predict a potential binding site at the CDK2/cyclin E1 interface.
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 217
2024-07-11 15:23:21,423 - INFO - Annotation: cyclin A., Type: GeneOrGeneProduct, Position: 238
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 324
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 430
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 490
2024-07-11 15:23:21,423 - INFO - Annotation: cyclin A1, E, and O, Type: GeneOrGeneProduct, Position: 495
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 636
2024-07-11 15:23:21,423 - INFO - Annotation: cyclin, Type: GeneOrGeneProduct, Position: 641
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 688
2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 769
2024-07-11 15:23:21,423 - INFO - Annotation: cyclin E1, Type: GeneOrGeneProduct, Position: 774
2024-07-11 15:23:21,423 - INFO - Document ID: BC8_BioRED_Task1_Doc1487
2024-07-11 15:23:21,424 - INFO - Text Instance: Cutaneous angiosarcoma treated with taxane-based chemoradiotherapy: A multicenter study of 90 Japanese cases.
2024-07-11 15:23:21,424 - INFO - Annotation: Cutaneous angiosarcoma, Type: DiseaseOrPhenotypicFeature, Position: 0
2024-07-11 15:23:21,424 - INFO - Annotation: taxane, Type: ChemicalEntity, Position: 36
2024-07-11 15:23:21,424 - INFO - Text Instance: Cutaneous angiosarcoma (CAS) is rare and most previous studies of CAS have been small case series, and randomized, phase II studies of CAS are limited. Since treatment options for CAS are controversial, and because only paclitaxel should be recommended based on high-level evidence, it is important to evaluate the efficacy of another taxane-derived agents, docetaxel, in real-world practice. The efficacy and safety profiles of chemoradiotherapy using taxane-based agents, docetaxel and paclitaxel, were retrospectively examined in the maintenance setting in 90 Japanese CAS patients, including 35 docetaxel-treated cases and 55 paclitaxel-treated cases. Overall survival and dose duration time of the patient group treated with docetaxel was equivalent to that with paclitaxel, even in the cohorts with metastasis. Adverse events due to docetaxel and paclitaxel were observed in 77.1% and 69.1% of cases, respectively. The incidence ratio of total severe adverse events tended to be higher in the docetaxel-treated group (40.0%) than in the paclitaxel-treated group (23.6%). Peripheral neuropathy occurred only in the paclitaxel-treated group, whereas high-grade interstitial pneumonia developed only in the docetaxel-treated group. In addition, we also evaluate 19 patients selected other taxanes, 17 patients selected eribulin methylate, 11 patients pazopanib, and 2 patients selected nivolumab as second-line chemotherapy. The efficacy of a monthly docetaxel regimen is equivalent to a three-weekly paclitaxel regimen evaluated by Overall survival and DDT, even in the cohorts with metastasis, and it is a tolerable protocol for CAS as a maintenance therapy in the Japanese population.
2024-07-11 15:23:21,424 - INFO - Annotation: Cutaneous angiosarcoma, Type: DiseaseOrPhenotypicFeature, Position: 0
2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 24
2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 66
2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 135
2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 180
2024-07-11 15:23:21,424 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 220
2024-07-11 15:23:21,424 - INFO - Annotation: taxane, Type: ChemicalEntity, Position: 335
2024-07-11 15:23:21,424 - INFO - Annotation: taxane, Type: ChemicalEntity, Position: 453
2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 488
2024-07-11 15:23:21,425 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 572
2024-07-11 15:23:21,425 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 576
2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 630
2024-07-11 15:23:21,425 - INFO - Annotation: patient, Type: OrganismTaxon, Position: 703
2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 768
2024-07-11 15:23:21,425 - INFO - Annotation: metastasis, Type: DiseaseOrPhenotypicFeature, Position: 805
2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 853
2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 1043
2024-07-11 15:23:21,425 - INFO - Annotation: Peripheral neuropathy, Type: DiseaseOrPhenotypicFeature, Position: 1077
2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 1120
2024-07-11 15:23:21,425 - INFO - Annotation: interstitial pneumonia, Type: DiseaseOrPhenotypicFeature, Position: 1165
2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1268
2024-07-11 15:23:21,426 - INFO - Annotation: taxanes, Type: ChemicalEntity, Position: 1292
2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1304
2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1345
2024-07-11 15:23:21,426 - INFO - Annotation: pazopanib, Type: ChemicalEntity, Position: 1354
2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1371
2024-07-11 15:23:21,426 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 1504
2024-07-11 15:23:21,426 - INFO - Annotation: metastasis, Type: DiseaseOrPhenotypicFeature, Position: 1587
2024-07-11 15:23:21,426 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 1634
2024-07-11 15:23:21,426 - INFO - Document ID: BC8_BioRED_Task1_Doc1488
2024-07-11 15:23:21,426 - INFO - Text Instance: Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing Gastroscopy: A Randomized Controlled Study.
2024-07-11 15:23:21,426 - INFO - Annotation: Remimazolam, Type: ChemicalEntity, Position: 0
2024-07-11 15:23:21,426 - INFO - Annotation: Sufentanil, Type: ChemicalEntity, Position: 44
2024-07-11 15:23:21,426 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 66
2024-07-11 15:23:21,426 - INFO - Annotation: Liver Cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 80
2024-07-11 15:23:21,426 - INFO - Text Instance: BACKGROUND This prospective, randomized, controlled study evaluated the efficacy and safety of remimazolam tosilate sedation with adjuvant sufentanil, relative to propofol, for Chinese patients with liver cirrhosis undergoing gastroscopy. MATERIAL AND METHODS Patients with liver cirrhosis (n=148) aged 18-65 years and undergoing gastroscopy were randomly and equally allocated to receive either 0.107 mg/kg remimazolam tosilate (remimazolam group) or 2 mg/kg propofol. Patients received intravenous sufentanil 0.15 mug/kg before the study drug. If necessary, an additional dose of propofol 20 mg was used and repeated. The primary outcome was the satisfaction rating (satisfactory, fair, or unsatisfactory) of the endoscopist with the sedation. Secondary outcomes were complications (respiratory depression, apnea, body movement, bradycardia, hypotension, nausea or vomiting, somnolence, dizziness, and fever) and patient satisfaction. RESULTS Compared with the propofol group, the remimazolam group required a longer time to sedation and a shorter time to emergence. The percentage of remimazolam sedations the endoscopist rated satisfactory (90.5%) was higher than that for propofol (77.0%; P=0.026). Patients given remimazolam experienced lower rates of respiratory depression, body movement, and hypotension (2.7, 8.1, 4.1%, respectively), than did the propofol group (17.6, 23.0, 14.9%; P=0.003, 0.013, 0.025). The 2 groups were comparable regarding the other secondary outcomes. CONCLUSIONS For Chinese patients with liver cirrhosis undergoing gastroscopy, remimazolam tosilate with adjuvant sufentanil provides a satisfactory level of sedation with a good safety profile.
2024-07-11 15:23:21,426 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 95
2024-07-11 15:23:21,426 - INFO - Annotation: sufentanil, Type: ChemicalEntity, Position: 139
2024-07-11 15:23:21,427 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 163
2024-07-11 15:23:21,427 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 185
2024-07-11 15:23:21,427 - INFO - Annotation: liver cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 199
2024-07-11 15:23:21,427 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 260
2024-07-11 15:23:21,427 - INFO - Annotation: liver cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 274
2024-07-11 15:23:21,427 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 408
2024-07-11 15:23:21,427 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 430
2024-07-11 15:23:21,427 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 460
2024-07-11 15:23:21,427 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 470
2024-07-11 15:23:21,427 - INFO - Annotation: sufentanil, Type: ChemicalEntity, Position: 500
2024-07-11 15:23:21,427 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 582
2024-07-11 15:23:21,427 - INFO - Annotation: respiratory depression, Type: DiseaseOrPhenotypicFeature, Position: 785
2024-07-11 15:23:21,427 - INFO - Annotation: apnea, Type: DiseaseOrPhenotypicFeature, Position: 809
2024-07-11 15:23:21,427 - INFO - Annotation: body movement, Type: DiseaseOrPhenotypicFeature, Position: 816
2024-07-11 15:23:21,427 - INFO - Annotation: bradycardia, Type: DiseaseOrPhenotypicFeature, Position: 831
2024-07-11 15:23:21,427 - INFO - Annotation: hypotension, Type: DiseaseOrPhenotypicFeature, Position: 844
2024-07-11 15:23:21,427 - INFO - Annotation: nausea or vomiting, Type: DiseaseOrPhenotypicFeature, Position: 857
2024-07-11 15:23:21,428 - INFO - Annotation: somnolence, Type: DiseaseOrPhenotypicFeature, Position: 877
2024-07-11 15:23:21,428 - INFO - Annotation: dizziness, Type: DiseaseOrPhenotypicFeature, Position: 889
2024-07-11 15:23:21,428 - INFO - Annotation: fever, Type: DiseaseOrPhenotypicFeature, Position: 904
2024-07-11 15:23:21,428 - INFO - Annotation: patient, Type: OrganismTaxon, Position: 915
2024-07-11 15:23:21,428 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 963
2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 983
2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 1087
2024-07-11 15:23:21,428 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 1177
2024-07-11 15:23:21,428 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 1204
2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 1219
2024-07-11 15:23:21,428 - INFO - Annotation: respiratory depression, Type: DiseaseOrPhenotypicFeature, Position: 1258
2024-07-11 15:23:21,428 - INFO - Annotation: body movement, Type: DiseaseOrPhenotypicFeature, Position: 1282
2024-07-11 15:23:21,428 - INFO - Annotation: hypotension, Type: DiseaseOrPhenotypicFeature, Position: 1301
2024-07-11 15:23:21,428 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 1358
2024-07-11 15:23:21,428 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1510
2024-07-11 15:23:21,428 - INFO - Annotation: liver cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 1524
2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 1564
2024-07-11 15:23:21,428 - INFO - Annotation: sufentanil, Type: ChemicalEntity, Position: 1599
2024-07-11 15:23:21,429 - INFO - Document ID: BC8_BioRED_Task1_Doc1489
2024-07-11 15:23:21,429 - INFO - Text Instance: Downregulation of Stearoyl-CoA Desaturase 1 (SCD-1) Promotes Resistance to Imatinib in Chronic Myeloid Leukemia.
2024-07-11 15:23:21,429 - INFO - Annotation: Stearoyl-CoA Desaturase 1, Type: GeneOrGeneProduct, Position: 18
2024-07-11 15:23:21,429 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 45
2024-07-11 15:23:21,429 - INFO - Annotation: Imatinib, Type: ChemicalEntity, Position: 75
2024-07-11 15:23:21,429 - INFO - Annotation: Chronic Myeloid Leukemia, Type: DiseaseOrPhenotypicFeature, Position: 87
2024-07-11 15:23:21,429 - INFO - Text Instance: Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease resulting in the fusion of BCR and ABL genes and characterized by the presence of the reciprocal translocation t(9;22)(q34;q11). BCR-ABL, a product of the BCR-ABL fusion gene, is a structurally active tyrosine kinase and plays an important role in CML disease pathogenesis. Imatinib mesylate (IMA) is a strong and selective BCR-ABL tyrosine kinase inhibitor. Although IMA therapy is an effective treatment, patients may develop resistance to IMA therapy over time. This study investigated the possible genetic resistance mechanisms in patients developing resistance to IMA. We did DNA sequencing in order to detect BCR-ABL mutations, which are responsible for IMA resistance. Moreover, we analyzed the mRNA expression levels of genes responsible for apoptosis, such as BCL-2, P53, and other genes (SCD-1, PTEN). In a group of CML patients resistant to IMA, when compared with IMA-sensitive CML patients, a decrease in SCD-1 gene expression levels and an increase in BCL-2 gene expression levels was observed. In this case, the SCD-1 gene was thought to act as a tumor suppressor. The present study aimed to investigate the mechanisms involved in IMA resistance in CML patients and determine new targets that can be beneficial in choosing the effective treatment. Finally, the study suggests that the SCD-1 and BCL-2 genes may be mechanisms responsible for resistance.
2024-07-11 15:23:21,469 - INFO - Annotation: Chronic myeloid leukemia, Type: DiseaseOrPhenotypicFeature, Position: 0
2024-07-11 15:23:21,469 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 26
2024-07-11 15:23:21,469 - INFO - Annotation: hematopoietic stem cell disease, Type: DiseaseOrPhenotypicFeature, Position: 46
2024-07-11 15:23:21,470 - INFO - Annotation: BCR, Type: GeneOrGeneProduct, Position: 105
2024-07-11 15:23:21,470 - INFO - Annotation: ABL, Type: GeneOrGeneProduct, Position: 113
2024-07-11 15:23:21,470 - INFO - Annotation: BCR-ABL, Type: GeneOrGeneProduct, Position: 207
2024-07-11 15:23:21,470 - INFO - Annotation: BCR-ABL, Type: GeneOrGeneProduct, Position: 233
2024-07-11 15:23:21,470 - INFO - Annotation: tyrosine kinase, Type: GeneOrGeneProduct, Position: 279
2024-07-11 15:23:21,470 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 326
2024-07-11 15:23:21,470 - INFO - Annotation: Imatinib mesylate, Type: ChemicalEntity, Position: 352
2024-07-11 15:23:21,470 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 371
2024-07-11 15:23:21,470 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 446
2024-07-11 15:23:21,470 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 485
2024-07-11 15:23:21,470 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 520
2024-07-11 15:23:21,470 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 613
2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 647
2024-07-11 15:23:21,471 - INFO - Annotation: BCR-ABL, Type: GeneOrGeneProduct, Position: 693
2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 738
2024-07-11 15:23:21,471 - INFO - Annotation: BCL-2, Type: GeneOrGeneProduct, Position: 847
2024-07-11 15:23:21,471 - INFO - Annotation: P53, Type: GeneOrGeneProduct, Position: 854
2024-07-11 15:23:21,471 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 876
2024-07-11 15:23:21,471 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 883
2024-07-11 15:23:21,471 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 904
2024-07-11 15:23:21,471 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 908
2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 930
2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 954
2024-07-11 15:23:21,472 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 968
2024-07-11 15:23:21,472 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 972
2024-07-11 15:23:21,472 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 996
2024-07-11 15:23:21,472 - INFO - Annotation: BCL-2, Type: GeneOrGeneProduct, Position: 1044
2024-07-11 15:23:21,472 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 1105
2024-07-11 15:23:21,472 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 1140
2024-07-11 15:23:21,472 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 1224
2024-07-11 15:23:21,472 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 1242
2024-07-11 15:23:21,472 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1246
2024-07-11 15:23:21,472 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 1378
2024-07-11 15:23:21,472 - INFO - Annotation: BCL-2, Type: GeneOrGeneProduct, Position: 1388
2024-07-11 15:23:21,472 - INFO - Document ID: BC8_BioRED_Task1_Doc1490
2024-07-11 15:23:21,473 - INFO - Text Instance: 12-O-tetradecanoylphorbol-13-acetate Reduces Activation of Hepatic Stellate Cells by Inhibiting the Hippo Pathway Transcriptional Coactivator YAP.
2024-07-11 15:23:21,473 - INFO - Annotation: 12-O-tetradecanoylphorbol-13-acetate, Type: ChemicalEntity, Position: 0
2024-07-11 15:23:21,473 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 142
2024-07-11 15:23:21,473 - INFO - Text Instance: Although protein kinase C (PKC) regulates various biological activities, including cell proliferation, differentiation, migration, tissue remodeling, gene expression, and cell death, the antifibrotic effect of PKC in myofibroblasts is not fully understood. We investigated whether 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, reduced the activation of hepatic stellate cells (HSCs) and explored the involvement of the Hippo pathway transcriptional coactivator YAP. We analyzed the effect of TPA on the proliferation and expression of alpha-smooth muscle actin (SMA) in the LX-2 HSC line. We also analyzed the phosphorylation of the Hippo pathway molecules YAP and LATS1 and investigated YAP nuclear translocation. We examined whether Go 6983, a pan-PKC inhibitor, restored the TPA-inhibited activities of HSCs. Administration of TPA decreased the growth rate of LX-2 cells and inhibited the expression of alpha-SMA and collagen type I alpha 1 (COL1A1). In addition, TPA induced phosphorylation of PKCdelta, LATS1, and YAP and inhibited the nuclear translocation of YAP compared with the control. These TPA-induced phenomena were mostly ameliorated by Go 6983. Our results indicate that PKCdelta exerts an antifibrotic effect by inhibiting the Hippo pathway in HSCs. Therefore, PKCdelta and YAP can be used as therapeutic targets for the treatment of fibrotic diseases.
2024-07-11 15:23:21,473 - INFO - Annotation: protein kinase C, Type: GeneOrGeneProduct, Position: 9
2024-07-11 15:23:21,473 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 27
2024-07-11 15:23:21,473 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 210
2024-07-11 15:23:21,473 - INFO - Annotation: 12-O-tetradecanoylphorbol-13-acetate, Type: ChemicalEntity, Position: 281
2024-07-11 15:23:21,473 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 319
2024-07-11 15:23:21,473 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 327
2024-07-11 15:23:21,473 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 476
2024-07-11 15:23:21,474 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 507
2024-07-11 15:23:21,474 - INFO - Annotation: LX-2, Type: CellLine, Position: 589
2024-07-11 15:23:21,474 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 672
2024-07-11 15:23:21,474 - INFO - Annotation: LATS1, Type: GeneOrGeneProduct, Position: 680
2024-07-11 15:23:21,474 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 703
2024-07-11 15:23:21,474 - INFO - Annotation: Go 6983, Type: ChemicalEntity, Position: 750
2024-07-11 15:23:21,474 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 765
2024-07-11 15:23:21,474 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 793
2024-07-11 15:23:21,474 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 845
2024-07-11 15:23:21,474 - INFO - Annotation: LX-2, Type: CellLine, Position: 878
2024-07-11 15:23:21,474 - INFO - Annotation: alpha-SMA, Type: GeneOrGeneProduct, Position: 921
2024-07-11 15:23:21,474 - INFO - Annotation: collagen type I alpha 1, Type: GeneOrGeneProduct, Position: 935
2024-07-11 15:23:21,475 - INFO - Annotation: COL1A1, Type: GeneOrGeneProduct, Position: 960
2024-07-11 15:23:21,475 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 982
2024-07-11 15:23:21,475 - INFO - Annotation: PKCdelta, Type: GeneOrGeneProduct, Position: 1013
2024-07-11 15:23:21,475 - INFO - Annotation: LATS1, Type: GeneOrGeneProduct, Position: 1023
2024-07-11 15:23:21,475 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 1034
2024-07-11 15:23:21,475 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 1081
2024-07-11 15:23:21,475 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 1118
2024-07-11 15:23:21,475 - INFO - Annotation: Go 6983, Type: ChemicalEntity, Position: 1167
2024-07-11 15:23:21,475 - INFO - Annotation: PKCdelta, Type: GeneOrGeneProduct, Position: 1202
2024-07-11 15:23:21,475 - INFO - Annotation: PKCdelta, Type: GeneOrGeneProduct, Position: 1293
2024-07-11 15:23:21,475 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 1306
2024-07-11 15:23:21,475 - INFO - Annotation: fibrotic diseases, Type: DiseaseOrPhenotypicFeature, Position: 1366
2024-07-11 15:23:21,476 - INFO - Document ID: BC8_BioRED_Task1_Doc1491
2024-07-11 15:23:21,476 - INFO - Text Instance: Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study.
2024-07-11 15:23:21,476 - INFO - Annotation: Memantine, Type: ChemicalEntity, Position: 28
2024-07-11 15:23:21,476 - INFO - Annotation: Masupirdine, Type: ChemicalEntity, Position: 57
2024-07-11 15:23:21,476 - INFO - Annotation: SUVN-502, Type: ChemicalEntity, Position: 70
2024-07-11 15:23:21,476 - INFO - Text Instance: INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT6) receptors, which are exclusively localized to the central nervous system, is reported to play an important role in learning and memory. Masupirdine is a potent and selective 5-HT6 receptor antagonist with pro-cognitive properties in animal models of cognition. METHODS: The efficacy and safety of masupirdine were evaluated in patients with moderate AD concurrently treated with donepezil and memantine. A total of 564 patients were randomized in a 1:1:1 ratio. The study consisted of a 26-week double-blind treatment period. The primary efficacy outcome was the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). In exploratory post hoc analyses, patients were subdivided based on the use of memantine dosage forms and memantine plasma concentrations, to evaluate the impact of memantine on the efficacy of masupirdine. RESULTS: In an exploratory post hoc analysis, less worsening in cognition (ADAS-Cog 11 scores) was observed with masupirdine treatment as compared with placebo in patients whose trough memantine plasma concentrations were <= 100 ng/mL. CONCLUSIONS: Although prespecified study endpoints of the phase 2 study were not met, these exploratory post hoc subgroup observations are hypothesis-generating and suggest that the efficacy of masupirdine was adversely affected by concurrent therapy with memantine. Further assessment of masupirdine to determine its potential role as a treatment option for cognitive deficits associated with AD is warranted. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02580305).
2024-07-11 15:23:21,476 - INFO - Annotation: Alzheimer's disease, Type: DiseaseOrPhenotypicFeature, Position: 14
2024-07-11 15:23:21,476 - INFO - Annotation: AD, Type: DiseaseOrPhenotypicFeature, Position: 35
2024-07-11 15:23:21,476 - INFO - Annotation: neurodegenerative disorder, Type: DiseaseOrPhenotypicFeature, Position: 44
2024-07-11 15:23:21,476 - INFO - Annotation: Masupirdine, Type: ChemicalEntity, Position: 345
2024-07-11 15:23:21,476 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 506
2024-07-11 15:23:21,476 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 536
2024-07-11 15:23:21,476 - INFO - Annotation: AD, Type: DiseaseOrPhenotypicFeature, Position: 559
2024-07-11 15:23:21,476 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 602
2024-07-11 15:23:21,476 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 628
2024-07-11 15:23:21,477 - INFO - Annotation: Alzheimer's Disease, Type: DiseaseOrPhenotypicFeature, Position: 806
2024-07-11 15:23:21,477 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 986
2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1031
2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1058
2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1117
2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1146
2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1272
2024-07-11 15:23:21,477 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1322
2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1344
2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1589
2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1651
2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1684
2024-07-11 15:23:21,477 - INFO - Annotation: cognitive deficits, Type: DiseaseOrPhenotypicFeature, Position: 1754
2024-07-11 15:23:21,477 - INFO - Annotation: AD, Type: DiseaseOrPhenotypicFeature, Position: 1789
2024-07-11 15:23:21,477 - INFO - Document ID: BC8_BioRED_Task1_Doc1492
2024-07-11 15:23:21,478 - INFO - Text Instance: ACE2 internalization induced by a SARS-CoV-2 recombinant protein is modulated by angiotensin II type 1 and bradykinin 2 receptors.
2024-07-11 15:23:21,478 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 0
2024-07-11 15:23:21,478 - INFO - Annotation: SARS-CoV-2, Type: OrganismTaxon, Position: 34
2024-07-11 15:23:21,478 - INFO - Annotation: angiotensin II type 1 and bradykinin 2 receptors, Type: GeneOrGeneProduct, Position: 81
2024-07-11 15:23:21,478 - INFO - Text Instance: AIMS: Angiotensin-converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system (RAS) recently identified as the membrane receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we aim to study whether two receptors from RAS, the angiotensin receptor type 1 (AT1R) and the bradykinin 2 receptor (B2R) modulate ACE2 internalization induced by a recombinant receptor binding domain (RBD) of SARS-CoV-2 spike protein. Also, we investigated the impact of ACE2 coexpression on AT1R and B2R functionality. MATERIALS AND METHODS: To study ACE2 internalization, we assessed the distribution of green fluorescent protein (GFP) signal in HEK293T cells coexpressing GFP-tagged ACE2 and AT1R, or B2R, or AT1R plus B2R in presence of RBD alone or in combination with AT1R or B2R ligands. To estimate ACE2 internalization, we classified GFP signal distribution as plasma membrane uniform GFP (PMU-GFP), plasma membrane clustered GFP (PMC-GFP) or internalized GFP and calculated its relative frequency. Additionally, we investigated the effect of ACE2 coexpression on AT1R and B2R inhibitory action on voltage-gated calcium channels (CaV2.2) currents by patch-clamp technique. KEY FINDINGS: RBD induced ACE2-GFP internalization in a time-dependent manner. RBD-induced ACE2-GFP internalization was increased by angiotensin II and reduced by telmisartan in cells coexpressing AT1R. RBD-induced ACE2-GFP internalization was strongly inhibited by B2R co-expression. This effect was mildly modified by bradykinin and rescued by angiotensin II in presence of AT1R. ACE2 coexpression impacted on B2R- and AT1R-mediated inhibition of CaV2.2 currents. SIGNIFICANCE: Our work contributes to understand the role of RAS modulators in the susceptibility to SARS-CoV-2 infection and severity of COVID-19.
2024-07-11 15:23:21,478 - INFO - Annotation: Angiotensin-converting enzyme 2, Type: GeneOrGeneProduct, Position: 6
2024-07-11 15:23:21,478 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 39
2024-07-11 15:23:21,478 - INFO - Annotation: renin, Type: GeneOrGeneProduct, Position: 71
2024-07-11 15:23:21,478 - INFO - Annotation: angiotensin, Type: GeneOrGeneProduct, Position: 77
2024-07-11 15:23:21,478 - INFO - Annotation: severe acute respiratory syndrome coronavirus 2, Type: OrganismTaxon, Position: 155
2024-07-11 15:23:21,478 - INFO - Annotation: SARS-CoV-2, Type: OrganismTaxon, Position: 204
2024-07-11 15:23:21,478 - INFO - Annotation: angiotensin receptor type 1, Type: GeneOrGeneProduct, Position: 274
2024-07-11 15:23:21,478 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 303
2024-07-11 15:23:21,478 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 340
2024-07-11 15:23:21,478 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 354
2024-07-11 15:23:21,478 - INFO - Annotation: SARS-CoV-2, Type: OrganismTaxon, Position: 433
2024-07-11 15:23:21,479 - INFO - Annotation: spike, Type: GeneOrGeneProduct, Position: 444
2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 495
2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 516
2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 525
2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 576
2024-07-11 15:23:21,479 - INFO - Annotation: HEK293T, Type: CellLine, Position: 672
2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 710
2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 719
2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 728
2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 736
2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 746
2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 798
2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 806
2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 831
2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1076
2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 1097
2024-07-11 15:23:21,480 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 1106
2024-07-11 15:23:21,480 - INFO - Annotation: calcium, Type: ChemicalEntity, Position: 1145
2024-07-11 15:23:21,480 - INFO - Annotation: CaV2.2, Type: GeneOrGeneProduct, Position: 1163
2024-07-11 15:23:21,480 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1232
2024-07-11 15:23:21,480 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1297
2024-07-11 15:23:21,480 - INFO - Annotation: angiotensin II, Type: GeneOrGeneProduct, Position: 1339
2024-07-11 15:23:21,480 - INFO - Annotation: AT1R., Type: GeneOrGeneProduct, Position: 1403
2024-07-11 15:23:21,480 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1421
2024-07-11 15:23:21,480 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 1472
2024-07-11 15:23:21,480 - INFO - Annotation: bradykinin, Type: GeneOrGeneProduct, Position: 1526
2024-07-11 15:23:21,480 - INFO - Annotation: angiotensin II, Type: GeneOrGeneProduct, Position: 1552
2024-07-11 15:23:21,482 - INFO - Annotation: AT1R., Type: GeneOrGeneProduct, Position: 1582
2024-07-11 15:23:21,482 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1588
2024-07-11 15:23:21,482 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 1618
2024-07-11 15:23:21,482 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 1627
2024-07-11 15:23:21,482 - INFO - Annotation: CaV2.2, Type: GeneOrGeneProduct, Position: 1655
2024-07-11 15:23:21,482 - INFO - Annotation: SARS-CoV-2 infection, Type: DiseaseOrPhenotypicFeature, Position: 1773
2024-07-11 15:23:21,482 - INFO - Annotation: COVID-19, Type: DiseaseOrPhenotypicFeature, Position: 1810
2024-07-11 15:23:21,482 - INFO - Document ID: BC8_BioRED_Task1_Doc1493
2024-07-11 15:23:21,482 - INFO - Text Instance: Ultrasound and laser-promoted dual-gas nano-generator for combined photothermal and immune tumor therapy.
2024-07-11 15:23:21,482 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 91
2024-07-11 15:23:21,482 - INFO - Text Instance: The combination of photothermal therapy (PTT) and immune tumor therapy has emerged as a promising avenue for cancer treatment. However, the insufficient immune response caused by inefficient immunogenic cell death (ICD) inducers and thermal resistance, immunosuppression, and immune escape resulting from the hypoxic microenvironment of solid tumors severely limit its efficacy. Herein, we report an ultrasound and laser-promoted dual-gas nano-generator (calcium carbonate-polydopamine-manganese oxide nanoparticles, CPM NPs) for enhanced photothermal/immune tumor therapy through reprogramming tumor hypoxic microenvironment. In this system, CPM NPs undergo reactive decomposition in a moderately acidic tumor, resulting in the generation of calcium, manganese ions, carbon dioxide (CO2), and oxygen (O2). Calcium and manganese ions act as adjuvants that trigger an immune response. The cancer cell membrane rupture caused by sudden burst of bubbles (CO2 and O2) under ultrasound stimulation and the photothermal properties of PDA also contributed to the ICD effect. The generation of O2 alleviates tumor hypoxia and thus reduces hypoxia-induced heat resistance and immunosuppressive effects, thereby improving the therapeutic efficacy of combination PTT and immune therapy. The present study provides a novel approach for the fabrication of a safe and effective tumor treatment platform for future clinical applications.
2024-07-11 15:23:21,482 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 57
2024-07-11 15:23:21,482 - INFO - Annotation: cancer, Type: DiseaseOrPhenotypicFeature, Position: 109
2024-07-11 15:23:21,483 - INFO - Annotation: hypoxic, Type: DiseaseOrPhenotypicFeature, Position: 309
2024-07-11 15:23:21,483 - INFO - Annotation: solid tumors, Type: DiseaseOrPhenotypicFeature, Position: 337
2024-07-11 15:23:21,483 - INFO - Annotation: calcium carbonate, Type: ChemicalEntity, Position: 455
2024-07-11 15:23:21,483 - INFO - Annotation: polydopamine, Type: ChemicalEntity, Position: 473
2024-07-11 15:23:21,483 - INFO - Annotation: manganese oxide, Type: ChemicalEntity, Position: 486
2024-07-11 15:23:21,483 - INFO - Annotation: CPM, Type: ChemicalEntity, Position: 517
2024-07-11 15:23:21,483 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 559
2024-07-11 15:23:21,483 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 595
2024-07-11 15:23:21,483 - INFO - Annotation: hypoxic, Type: DiseaseOrPhenotypicFeature, Position: 601
2024-07-11 15:23:21,483 - INFO - Annotation: CPM, Type: ChemicalEntity, Position: 643
2024-07-11 15:23:21,483 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 705
2024-07-11 15:23:21,483 - INFO - Annotation: calcium, Type: ChemicalEntity, Position: 743
2024-07-11 15:23:21,483 - INFO - Annotation: manganese, Type: ChemicalEntity, Position: 752
2024-07-11 15:23:21,483 - INFO - Annotation: carbon dioxide, Type: ChemicalEntity, Position: 768
2024-07-11 15:23:21,483 - INFO - Annotation: CO2, Type: ChemicalEntity, Position: 784
2024-07-11 15:23:21,484 - INFO - Annotation: oxygen, Type: ChemicalEntity, Position: 794
2024-07-11 15:23:21,484 - INFO - Annotation: O2, Type: ChemicalEntity, Position: 802
2024-07-11 15:23:21,484 - INFO - Annotation: Calcium, Type: ChemicalEntity, Position: 807
2024-07-11 15:23:21,484 - INFO - Annotation: manganese, Type: ChemicalEntity, Position: 819
2024-07-11 15:23:21,484 - INFO - Annotation: cancer, Type: DiseaseOrPhenotypicFeature, Position: 888
2024-07-11 15:23:21,484 - INFO - Annotation: CO2, Type: ChemicalEntity, Position: 952
2024-07-11 15:23:21,484 - INFO - Annotation: O2, Type: ChemicalEntity, Position: 960
2024-07-11 15:23:21,484 - INFO - Annotation: O2, Type: ChemicalEntity, Position: 1086
2024-07-11 15:23:21,484 - INFO - Annotation: tumor hypoxia, Type: DiseaseOrPhenotypicFeature, Position: 1100
2024-07-11 15:23:21,484 - INFO - Annotation: hypoxia, Type: DiseaseOrPhenotypicFeature, Position: 1131
2024-07-11 15:23:21,484 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 1364
2024-07-11 15:23:21,484 - INFO - Document ID: BC8_BioRED_Task1_Doc1494
2024-07-11 15:23:21,484 - INFO - Text Instance: RanBP9 controls the oligomeric state of CTLH complex assemblies.
2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 0
2024-07-11 15:23:21,485 - INFO - Text Instance: The CTLH complex is a multisubunit RING E3 ligase with poorly defined substrate specificity and flexible subunit composition. Two key subunits, Muskelin and Wdr26, specify two alternative CTLH complexes that differ in quaternary structure, thereby allowing the E3 ligase to presumably target different substrates. With the aid of different biophysical and biochemical techniques we characterized CTLH complex assembly pathways, focusing not only on Wdr26 and Muskelin, but also on the RanBP9, Twa1 and Armc8beta subunits, which are critical to establish the scaffold of this E3 ligase. We demonstrate that the ability of Muskelin to tetramerize and the assembly of Wdr26 into dimers define mutually exclusive oligomerization modules that compete with nanomolar affinity for RanBP9 binding. The remaining scaffolding subunits, Armc8beta and Twa1, strongly interact with each other and with RanBP9, again with nanomolar affinity. Our data demonstrate that RanBP9 organizes subunit assembly and prevents higher order oligomerization of dimeric Wdr26 and the Armc8beta-Twa1 heterodimer through its tight binding. Combined, our studies define alternative assembly pathways of the CTLH complex and elucidate the role of RanBP9 in governing differential oligomeric assemblies, thereby, advancing our mechanistic understanding of CTLH complex architectures.
2024-07-11 15:23:21,485 - INFO - Annotation: Muskelin, Type: GeneOrGeneProduct, Position: 144
2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 157
2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 449
2024-07-11 15:23:21,485 - INFO - Annotation: Muskelin, Type: GeneOrGeneProduct, Position: 459
2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 485
2024-07-11 15:23:21,485 - INFO - Annotation: Twa1, Type: GeneOrGeneProduct, Position: 493
2024-07-11 15:23:21,485 - INFO - Annotation: Muskelin, Type: GeneOrGeneProduct, Position: 621
2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 665
2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 774
2024-07-11 15:23:21,485 - INFO - Annotation: Twa1, Type: GeneOrGeneProduct, Position: 840
2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 889
2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 954
2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 1041
2024-07-11 15:23:21,485 - INFO - Annotation: Twa1, Type: GeneOrGeneProduct, Position: 1065
2024-07-11 15:23:21,486 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 1214
2024-07-11 15:23:21,486 - INFO - Document ID: BC8_BioRED_Task1_Doc1495
2024-07-11 15:23:21,486 - INFO - Text Instance: The Comparison of the Influence of Bisphenol A (BPA) and Its Analogue Bisphenol S (BPS) on the Enteric Nervous System of the Distal Colon in Mice.
2024-07-11 15:23:21,486 - INFO - Annotation: Bisphenol A, Type: ChemicalEntity, Position: 35
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 48
2024-07-11 15:23:21,486 - INFO - Annotation: Bisphenol S, Type: ChemicalEntity, Position: 70
2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 83
2024-07-11 15:23:21,486 - INFO - Annotation: Mice, Type: OrganismTaxon, Position: 141
2024-07-11 15:23:21,486 - INFO - Text Instance: Bisphenol A (BPA), commonly used as a plasticizer in various branches of industry has a strong negative effect on living organisms. Therefore, more and more often it is replaced in production of plastics by other substances. One of them is bisphenol S (BPS). This study for the first time compares the impact of BPA and BPS on the enteric neurons using double immunofluorescence technique. It has been shown that both BPA and BPS affect the number of enteric neurons containing substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), neuronal isoform of nitric oxide synthase (nNOS-a marker of nitrergic neurons) and/or vesicular acetylcholine transporter (VAChT- a marker of cholinergic neurons). The changes noted under the impact of both bisphenols are similar and consisted of an increase in the number of enteric neurons immunoreactive to all neuronal factors studied. The impact of BPS on some populations of neurons was stronger than that noted under the influence of BPA. The obtained results clearly show that BPS (similarly to BPA) administered for long time is not neutral for the enteric neurons even in relatively low doses and may be more potent than BPA for certain neuronal populations.
2024-07-11 15:23:21,486 - INFO - Annotation: Bisphenol A, Type: ChemicalEntity, Position: 0
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 13
2024-07-11 15:23:21,486 - INFO - Annotation: bisphenol S, Type: ChemicalEntity, Position: 240
2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 253
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 312
2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 320
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 418
2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 426
2024-07-11 15:23:21,486 - INFO - Annotation: substance P, Type: GeneOrGeneProduct, Position: 478
2024-07-11 15:23:21,486 - INFO - Annotation: galanin, Type: GeneOrGeneProduct, Position: 496
2024-07-11 15:23:21,486 - INFO - Annotation: GAL, Type: GeneOrGeneProduct, Position: 505
2024-07-11 15:23:21,486 - INFO - Annotation: vasoactive intestinal polypeptide, Type: GeneOrGeneProduct, Position: 511
2024-07-11 15:23:21,486 - INFO - Annotation: VIP, Type: GeneOrGeneProduct, Position: 546
2024-07-11 15:23:21,486 - INFO - Annotation: nNOS, Type: GeneOrGeneProduct, Position: 595
2024-07-11 15:23:21,486 - INFO - Annotation: vesicular acetylcholine transporter, Type: GeneOrGeneProduct, Position: 638
2024-07-11 15:23:21,486 - INFO - Annotation: VAChT, Type: GeneOrGeneProduct, Position: 675
2024-07-11 15:23:21,486 - INFO - Annotation: bisphenols, Type: ChemicalEntity, Position: 759
2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 906
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 993
2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 1037
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 1055
2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 1183
2024-07-11 15:23:21,487 - INFO - Document ID: BC8_BioRED_Task1_Doc1496
2024-07-11 15:23:21,487 - INFO - Text Instance: PTPRM methylation induced by FN1 promotes the development of glioblastoma by activating STAT3 signalling.
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 0
2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 29
2024-07-11 15:23:21,487 - INFO - Annotation: glioblastoma, Type: DiseaseOrPhenotypicFeature, Position: 61
2024-07-11 15:23:21,487 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 88
2024-07-11 15:23:21,487 - INFO - Text Instance: CONTEXT: The phosphorylation of signal transducer and activator of transcription protein 3 (STAT3) is up-regulated in glioblastoma (GBM) cells and is regulated by protein tyrosine phosphatase receptor type M (PTPRM). Fibronectin-1 (FN1) is also reported to be up-regulated in GBM. OBJECTIVE: We explored the role of FN1-induced PTPRM methylation in GBM. MATERIALS AND METHODS: The lentivirus particles of oe-PTPRM, sh-PTPRM, oe-FN1, sh-FN1, or their negative controls (NSCs) were transfected into GBM cells with or without stattic (0.5 muM, 24 h) or 5-aza (1 muM, 0, 2, 4 h) treatments. Methylation-specific PCR was performed to detect PTPRM methylation levels. RESULTS: PTPRM was down-regulated (0.373 +- 0.124- and 0.455 +- 0.109-fold), FN1 and p-STAT3 were up-regulated (p < 0.001) in A172 and U87 MG cells as compared to NSCs. Overexpressing PTPRM inhibited STAT3 phosphorylation. Interfering with PTPRM increased colony numbers in A172 and U-87 MG cells (2.253 +- 0.111- and 2.043 +- 0.19-fold), and stattic reduced them. Cell viability was reduced after treatment with 5-aza in A172 and U-87 MG cells (p < 0.05). P-STAT3 was down-regulated after 5-aza treatment. Overexpressing FN1 decreased PTPRM levels (p < 0.001), knockdown of FN1 decreased PTPRM methylation and inhibited STAT3 phosphorylation. Overexpressing FN1 increased cell viability (1.497 +- 0.114- and 1.460 +- 0.151-fold), and stattic or 5-aza reversed such effects (p < 0.05). DISCUSSION AND CONCLUSIONS: The up-regulation of FN1 reduced PTPRM by increasing its methylation, resulting in an increase of STAT3 phosphorylation and promoting GBM cell proliferation. Interfering with FN1 may be a potential therapeutic target for GBM.
2024-07-11 15:23:21,487 - INFO - Annotation: signal transducer and activator of transcription protein 3, Type: GeneOrGeneProduct, Position: 32
2024-07-11 15:23:21,487 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 92
2024-07-11 15:23:21,487 - INFO - Annotation: glioblastoma, Type: DiseaseOrPhenotypicFeature, Position: 118
2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 132
2024-07-11 15:23:21,487 - INFO - Annotation: protein tyrosine phosphatase receptor type M, Type: GeneOrGeneProduct, Position: 163
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 209
2024-07-11 15:23:21,487 - INFO - Annotation: Fibronectin-1, Type: GeneOrGeneProduct, Position: 217
2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 232
2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 276
2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 316
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 328
2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 349
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 408
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 418
2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 428
2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 436
2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 497
2024-07-11 15:23:21,487 - INFO - Annotation: stattic, Type: ChemicalEntity, Position: 523
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 636
2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 671
2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 739
2024-07-11 15:23:21,487 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 749
2024-07-11 15:23:21,487 - INFO - Annotation: A172, Type: CellLine, Position: 788
2024-07-11 15:23:21,487 - INFO - Annotation: U87 MG, Type: CellLine, Position: 797
2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 846
2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 862
2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 902
2024-07-11 15:23:21,488 - INFO - Annotation: A172, Type: CellLine, Position: 936
2024-07-11 15:23:21,488 - INFO - Annotation: U-87 MG, Type: CellLine, Position: 945
2024-07-11 15:23:21,488 - INFO - Annotation: stattic, Type: ChemicalEntity, Position: 1005
2024-07-11 15:23:21,488 - INFO - Annotation: A172, Type: CellLine, Position: 1084
2024-07-11 15:23:21,488 - INFO - Annotation: U-87 MG, Type: CellLine, Position: 1093
2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 1121
2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1184
2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 1198
2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1237
2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 1251
2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 1283
2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1321
2024-07-11 15:23:21,488 - INFO - Annotation: stattic, Type: ChemicalEntity, Position: 1397
2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1497
2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 1509
2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 1574
2024-07-11 15:23:21,488 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 1610
2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1651
2024-07-11 15:23:21,488 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 1697
2024-07-11 15:23:21,488 - INFO - Document ID: BC8_BioRED_Task1_Doc1497
2024-07-11 15:23:21,488 - INFO - Text Instance: Screening and verification of genes related to polycystic ovary syndrome.
2024-07-11 15:23:21,488 - INFO - Annotation: polycystic ovary syndrome, Type: DiseaseOrPhenotypicFeature, Position: 47
2024-07-11 15:23:21,532 - INFO - Text Instance: OBJECTIVE: To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). METHODS: By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. RESULTS: From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. CONCLUSIONS: ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy.
2024-07-11 15:23:21,532 - INFO - Annotation: polycystic ovary syndrome, Type: DiseaseOrPhenotypicFeature, Position: 75
2024-07-11 15:23:21,532 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 102
2024-07-11 15:23:21,533 - INFO - Annotation: women, Type: OrganismTaxon, Position: 287
2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 298
2024-07-11 15:23:21,533 - INFO - Annotation: women, Type: OrganismTaxon, Position: 433
2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 444
2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 596
2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 605
2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 677
2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 689
2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 698
2024-07-11 15:23:21,533 - INFO - Annotation: women, Type: OrganismTaxon, Position: 742
2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 753
2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 792
2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 801
2024-07-11 15:23:21,533 - INFO - Annotation: testosterone, Type: ChemicalEntity, Position: 838
2024-07-11 15:23:21,533 - INFO - Annotation: cholesterol, Type: ChemicalEntity, Position: 852
2024-07-11 15:23:21,533 - INFO - Annotation: triglycerides, Type: ChemicalEntity, Position: 869
2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 884
2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 965
2024-07-11 15:23:21,534 - INFO - Annotation: ORM, Type: GeneOrGeneProduct, Position: 1025
2024-07-11 15:23:21,534 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 1080
2024-07-11 15:23:21,534 - INFO - Document ID: BC8_BioRED_Task1_Doc1498
2024-07-11 15:23:21,534 - INFO - Text Instance: Inhibitors of EYA3 Protein in Ewing Sarcoma.
2024-07-11 15:23:21,534 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 14
2024-07-11 15:23:21,534 - INFO - Annotation: Ewing Sarcoma, Type: DiseaseOrPhenotypicFeature, Position: 30
2024-07-11 15:23:21,534 - INFO - Text Instance: OBJECTIVE: Among sarcomas, Ewing sarcoma (EWS) is characterized as a highly malignant type of bone tumor caused by the fusion of EWS RNA Binding Protein-1 (EWSR1)/ Friend leukemia integration 1 (FLI1) genes. The product of fusion gene gives rise to EWSR1/FLI1 which activates the activity of Eyes absent homolog 3 (EYA3) which causes tumor growth and angiogenesis. EYA3 is now considered as a therapeutic drug target for EWS . The study was designed to gather potential inhibitors for the EYA3 target using medicinal compounds. METHODS: In this study, we have obtained a list of medicinal compounds from the NuBBE database and downloaded their structural information. Then insilico screening analysis of >2,000 medicinal compounds was performed with PyRX virtual drug screening software to discover potential inhibitors for the treatment of EWS. RESULTS: Our investigation revealed that Sorbifolin and 1,7-Dihydroxy-3-methylanthracene-9.10-dione show interactive affinity for EYA3 active residues. Moreover, these compounds have adequate toxicity, can induce cytotoxicity in EWS cells, and are capable of regulating the expression of genes activated by EWSR1/FLI1. CONCLUSION: Our study concluded that Sorbifolin and 1,7-Dihydroxy-3-methylanthracene-9.10-dione are promising drug candidates for the treatment of EWS and should be further subjected to invitro testing.
2024-07-11 15:23:21,534 - INFO - Annotation: sarcomas, Type: DiseaseOrPhenotypicFeature, Position: 17
2024-07-11 15:23:21,534 - INFO - Annotation: Ewing sarcoma, Type: DiseaseOrPhenotypicFeature, Position: 27
2024-07-11 15:23:21,534 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 42
2024-07-11 15:23:21,534 - INFO - Annotation: bone tumor, Type: DiseaseOrPhenotypicFeature, Position: 94
2024-07-11 15:23:21,534 - INFO - Annotation: EWS RNA Binding Protein-1, Type: GeneOrGeneProduct, Position: 129
2024-07-11 15:23:21,534 - INFO - Annotation: EWSR1, Type: GeneOrGeneProduct, Position: 156
2024-07-11 15:23:21,534 - INFO - Annotation: Friend leukemia integration 1, Type: GeneOrGeneProduct, Position: 164
2024-07-11 15:23:21,534 - INFO - Annotation: FLI1, Type: GeneOrGeneProduct, Position: 195
2024-07-11 15:23:21,534 - INFO - Annotation: EWSR1, Type: GeneOrGeneProduct, Position: 249
2024-07-11 15:23:21,534 - INFO - Annotation: FLI1, Type: GeneOrGeneProduct, Position: 255
2024-07-11 15:23:21,535 - INFO - Annotation: Eyes absent homolog 3, Type: GeneOrGeneProduct, Position: 292
2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 315
2024-07-11 15:23:21,535 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 334
2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 365
2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 421
2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 489
2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 841
2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 976
2024-07-11 15:23:21,535 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 1038
2024-07-11 15:23:21,535 - INFO - Annotation: cytotoxicity, Type: DiseaseOrPhenotypicFeature, Position: 1059
2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 1075
2024-07-11 15:23:21,535 - INFO - Annotation: EWSR1, Type: GeneOrGeneProduct, Position: 1153
2024-07-11 15:23:21,535 - INFO - Annotation: FLI1, Type: GeneOrGeneProduct, Position: 1159
2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 1312
2024-07-11 15:23:21,535 - INFO - Document ID: BC8_BioRED_Task1_Doc1499
2024-07-11 15:23:21,535 - INFO - Text Instance: A randomized, double-blind, multicenter, phase III study on the efficacy and safety of a combination treatment involving fimasartan, amlodipine, rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy.
2024-07-11 15:23:21,535 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 121
2024-07-11 15:23:21,536 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 133
2024-07-11 15:23:21,536 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 145
2024-07-11 15:23:21,536 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 161
2024-07-11 15:23:21,536 - INFO - Annotation: hypertension, Type: DiseaseOrPhenotypicFeature, Position: 185
2024-07-11 15:23:21,536 - INFO - Annotation: dyslipidemia, Type: DiseaseOrPhenotypicFeature, Position: 202
2024-07-11 15:23:21,536 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 249
2024-07-11 15:23:21,536 - INFO - Text Instance: BACKGROUND: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. METHODS: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. RESULTS: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions. CONCLUSIONS: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. TRIAL REGISTRATION: NCT03156842, Registered 17 May 2017.
2024-07-11 15:23:21,536 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 81
2024-07-11 15:23:21,536 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 93
2024-07-11 15:23:21,536 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 109
2024-07-11 15:23:21,536 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 125
2024-07-11 15:23:21,536 - INFO - Annotation: hypertension, Type: DiseaseOrPhenotypicFeature, Position: 149
2024-07-11 15:23:21,536 - INFO - Annotation: dyslipidemia, Type: DiseaseOrPhenotypicFeature, Position: 166
2024-07-11 15:23:21,536 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 202
2024-07-11 15:23:21,536 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 337
2024-07-11 15:23:21,537 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 426
2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 471
2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 536
2024-07-11 15:23:21,537 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 553
2024-07-11 15:23:21,537 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 572
2024-07-11 15:23:21,537 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 596
2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 623
2024-07-11 15:23:21,537 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 640
2024-07-11 15:23:21,537 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 662
2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 691
2024-07-11 15:23:21,537 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 710
2024-07-11 15:23:21,537 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1162
2024-07-11 15:23:21,537 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 1386
2024-07-11 15:23:21,538 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 1504
2024-07-11 15:23:21,538 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 1707
2024-07-11 15:23:21,538 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 1718
2024-07-11 15:23:21,538 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 1731
2024-07-11 15:23:21,538 - INFO - Annotation: lipid, Type: ChemicalEntity, Position: 1824
2024-07-11 15:23:21,538 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1840
2024-07-11 15:23:21,538 - INFO - Annotation: hypertension, Type: DiseaseOrPhenotypicFeature, Position: 1864
2024-07-11 15:23:21,538 - INFO - Annotation: dyslipidemia, Type: DiseaseOrPhenotypicFeature, Position: 1881
2024-07-11 15:23:21,538 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 1928
2024-07-11 15:23:23,707 - INFO - number_unique_YES_instances: 0
number_unique_YES_instances 0
number_unique_YES_instances: 0
2024-07-11 15:23:24,048 - INFO - Successfully wrote output TSV file: out_processed.tsv
Generating RE predictions
2024-07-11 15:23:26.139808: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcudart.so.11.0'; dlerror: libcudart.so.11.0: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server
2024-07-11 15:23:26.139857: I tensorflow/stream_executor/cuda/cudart_stub.cc:29] Ignore above cudart dlerror if you do not have a GPU set up on your machine.
[INFO|training_args.py:804] 2024-07-11 15:23:29,325 >> using logging_steps to initialize eval_steps to 10
[INFO|training_args.py:1023] 2024-07-11 15:23:29,325 >> PyTorch: setting up devices
[INFO|training_args.py:885] 2024-07-11 15:23:29,326 >> The default value for the training argument --report_to will change in v5 (from all installed integrations to none). In v5, you will need to use --report_to all to get the same behavior as now. You should start updating your code and make this info disappear :-).
INFO:main:Starting prediction
ERROR:main:Error during prediction: local variable 'processor' referenced before assignment
[INFO|training_args_tf.py:189] 2024-07-11 15:23:29,326 >> Tensorflow: setting up strategy
2024-07-11 15:23:29.327332: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcuda.so.1'; dlerror: libcuda.so.1: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server
2024-07-11 15:23:29.327367: W tensorflow/stream_executor/cuda/cuda_driver.cc:269] failed call to cuInit: UNKNOWN ERROR (303)
2024-07-11 15:23:29.327392: I tensorflow/stream_executor/cuda/cuda_diagnostics.cc:156] kernel driver does not appear to be running on this host (BLOOM): /proc/driver/nvidia/version does not exist
2024-07-11 15:23:29.327937: I tensorflow/core/platform/cpu_feature_guard.cc:193] This TensorFlow binary is optimized with oneAPI Deep Neural Network Library (oneDNN) to use the following CPU instructions in performance-critical operations: AVX2 AVX512F FMA
To enable them in other operations, rebuild TensorFlow with the appropriate compiler flags.
INFO:main:n_replicas: 1, distributed training: False, 16-bits training: False
INFO:main:Training/evaluation parameters TFTrainingArguments(
_n_gpu=0,
adafactor=False,
adam_beta1=0.9,
adam_beta2=0.999,
adam_epsilon=1e-08,
bf16=False,
bf16_full_eval=False,
data_seed=None,
dataloader_drop_last=False,
dataloader_num_workers=0,
dataloader_pin_memory=True,
ddp_bucket_cap_mb=None,
ddp_find_unused_parameters=None,
debug=[],
deepspeed=None,
disable_tqdm=False,
do_eval=True,
do_predict=True,
do_train=False,
eval_accumulation_steps=None,
eval_delay=0,
eval_steps=10,
evaluation_strategy=IntervalStrategy.STEPS,
fp16=False,
fp16_backend=auto,
fp16_full_eval=False,
fp16_opt_level=O1,
gcp_project=None,
gradient_accumulation_steps=1,
gradient_checkpointing=False,
greater_is_better=None,
group_by_length=False,
half_precision_backend=auto,
hub_model_id=None,
hub_strategy=HubStrategy.EVERY_SAVE,
hub_token=<HUB_TOKEN>,
ignore_data_skip=False,
label_names=None,
label_smoothing_factor=0.0,
learning_rate=5e-05,
length_column_name=length,
load_best_model_at_end=False,
local_rank=-1,
log_level=-1,
log_level_replica=-1,
log_on_each_node=True,
logging_dir=biorex_model/runs/Jul11_15-23-29_BLOOM,
logging_first_step=False,
logging_nan_inf_filter=True,
logging_steps=10,
logging_strategy=IntervalStrategy.STEPS,
lr_scheduler_type=SchedulerType.LINEAR,
max_grad_norm=1.0,
max_steps=-1,
metric_for_best_model=None,
mp_parameters=,
no_cuda=False,
num_train_epochs=10.0,
optim=OptimizerNames.ADAMW_HF,
output_dir=biorex_model,
overwrite_output_dir=True,
past_index=-1,
per_device_eval_batch_size=32,
per_device_train_batch_size=16,
poly_power=1.0,
prediction_loss_only=False,
push_to_hub=False,
push_to_hub_model_id=None,
push_to_hub_organization=None,
push_to_hub_token=<PUSH_TO_HUB_TOKEN>,
remove_unused_columns=True,
report_to=['tensorboard'],
resume_from_checkpoint=None,
run_name=biorex_model,
save_on_each_node=False,
save_steps=10,
save_strategy=IntervalStrategy.STEPS,
save_total_limit=None,
seed=42,
sharded_ddp=[],
skip_memory_metrics=True,
tf32=None,
tpu_metrics_debug=False,
tpu_name=None,
tpu_num_cores=None,
tpu_zone=None,
use_legacy_prediction_loop=False,
warmup_ratio=0.0,
warmup_steps=0,
weight_decay=0.0,
xla=False,
xpu_backend=None,
)
INFO:main:Task: biorex
INFO:main:Data directory: None
ERROR:main:Error loading model or tokenizer: local variable 'new_special_tokens' referenced before assignment
cp: cannot stat 'biorex_model/test_results.tsv': No such file or directory
2024-07-11 15:23:32.327195: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcudart.so.11.0'; dlerror: libcudart.so.11.0: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server
2024-07-11 15:23:32.327239: I tensorflow/stream_executor/cuda/cudart_stub.cc:29] Ignore above cudart dlerror if you do not have a GPU set up on your machine.
2024-07-11 15:23:33.896950: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcuda.so.1'; dlerror: libcuda.so.1: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server
2024-07-11 15:23:33.896995: W tensorflow/stream_executor/cuda/cuda_driver.cc:269] failed call to cuInit: UNKNOWN ERROR (303)
2024-07-11 15:23:33.897018: I tensorflow/stream_executor/cuda/cuda_diagnostics.cc:156] kernel driver does not appear to be running on this host (BLOOM): /proc/driver/nvidia/version does not exist

@Darrshan-Sankar
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Hi @michaelanekson,

Thank you for sharing the files. I've taken a look at your sample file, and I noticed you're using PubTator NE types instead of BioRED NE types. If you've downloaded your sample file from PubTator, you can use the converter mentioned in this GitHub issue comment to convert it to BioRED NE types.

Since the NE type tags are different, it might negatively impact the script you provided. I'd recommend using our leaderboard's dataset and evaluation to test it before applying it to your own dataset.

Also, if you're only interested in results for PubMed abstracts, we've already processed the entire PubMed database. You can find that data here.

@ptlai is it possiblt to use the annotation created from AIONER?

@ptlai
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ptlai commented Jul 18, 2024

michaela95

Sorry for the late reply. It looks like you were attempting to run BioREx with the pretrained BioLinkBERT model to predict on the BC8_BioRED_Subtask1_PubTator/bc8_biored_task1_val.pubtator file. You then encountered the error you mentioned.

I tried replicating your setup, following the installation steps from https://github.com/ncbi/BioREx/?tab=readme-ov-file#installation. I'm running Windows 11 with WSL2 (Linux subsystem). Interestingly, I was able to run the prediction without any issues, as you can see in the attached screenshot.

image

To help troubleshoot, could you provide some more details? Such complete Python package versions and operating system. Thank you

@Darrshan-Sankar
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Darrshan-Sankar commented Jul 18, 2024

michaela95

Sorry for the late reply. It looks like you were attempting to run BioREx with the pretrained BioLinkBERT model to predict on the BC8_BioRED_Subtask1_PubTator/bc8_biored_task1_val.pubtator file. You then encountered the error you mentioned.

I tried replicating your setup, following the installation steps from https://github.com/ncbi/BioREx/?tab=readme-ov-file#installation. I'm running Windows 11 with WSL2 (Linux subsystem). Interestingly, I was able to run the prediction without any issues, as you can see in the attached screenshot.

image

To help troubleshoot, could you provide some more details? Such complete Python package versions and operating system. Thank you

@ptlai Thank you for your continuous support. The problem is not with setting up the project, but due to the input mismatch (PS: Which I found 1-2 days back), which has already been clarified by you in another thread (Link: #9 (comment)) today. Thanks..

@michaelanekson
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michaelanekson commented Jul 18, 2024

Thank you for the reply. I have already solved the problem. Let's say the problem is about the input. I tried the BioRED format and it works fine. The conclusion of this issue for the readers is the author's code (run_test_pred.sh) can run fluently for the CPU (when there's a CUDA or GPU-related error, just ignore it) and the input must be transformed from Pubtator format into BioRED format before the analysis. I close this issue.

Now, the situation is I have questions about the output and I need your advice.

@michaelanekson michaelanekson changed the title Can't run on CPU run_test_pred.sh can't run on CPU Jul 18, 2024
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