anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PURPOSE:To obtain a new substance D329, having excellent antitumor activity and high water solubility and useful as an anticancer agent with hardly any toxicity by culturing a microorganism, belonging to the genus Streptomyces and having the ability to produce the substance D329. CONSTITUTION:A microorganism [e.g. Streptomyces.chartreusis D329-185 strain (FERM BP-3269)], belonging to the genus Streptomyces and having the ability to produce the substance D329 expressed by formula I (R<1> is a group expressed by formula II, etc.; R<2> is a group expressed by formula III, etc.) or its derivative is inoculated into a culture medium and cultured at 30 deg.C for 4 days by shaking to prepare a primary culture solution, which is then inoculated into a culture medium and cultured at 30 deg.C for 16 days by shaking. The obtained culture solution is subsequently centrifuged to collect microbial cells. Acetone is then added to the resultant microbial cells and the prepared mixture is stirred at ambient temperature for 5hr to carry out the extraction. The resultant extract solution is concentrated under reduced pressure and the obtained concentrate is subsequently extracted with n-butanol to concentrate the extract solution under reduced pressure. The obtained crude extract is then purified by chromatography to afford the substance D329 (derivative), having the antitumor activity and expressed by formula I.
The retina is composed of neuronal layers that include several types of interneurons and photoreceptor cells, and separate underlying retinal pigment epithelium (RPE), Bruch's membrane, and choroid. Different regions of the human retina include the fovea, macula, and periphery, which have unique physiological functions and anatomical features. These regions are also unique in their protein expression, and corresponding cellular and molecular responses to physiological and pathophysiological stimuli. Skeie and Mahajan analyzed regional protein expression in the human choroid-RPE complex. Mitogen-Activated Protein Kinase (MAPK) signaling pathways have been implicated in responses to stimuli such as oxidative stress and inflammation, which are critical factors in retina diseases including age-related macular degeneration. We, therefore, analyzed the Skeie and Mahajan, 2014, dataset for regional differences in the expression of MAPK-related proteins and discussed the potential implications in retinal diseases presenting with regional signs and symptoms. Regional protein expression data from the Skeie and Mahajan, 2014, study were analyzed for members of signaling networks involving MAPK and MAPK-related proteins, categorized by specific MAPK cascades, such as p38, ERK1/2, and JNK1/2, both upstream or downstream of the respective MAPK and MAPK-related proteins. We were able to identify 207 MAPK and MAPK-related proteins, 187 of which belonging to specific MAPK cascades. A total of 31 of these had been identified in the retina with two proteins, DLG2 and FLG downstream, and the other 29 upstream, of MAPK proteins. Our findings provide evidence for potential molecular substrates of retina region-specific disease manifestation and potential new targets for therapeutics development.
Histological observation under light microscopy has long been used in human cadaveric studies. However, it can distort the interpretations of findings if not used appropriately; there is no guide for its proper use. The aim of this article is to revisit and discuss the correct use of histology in human cadaveric studies, following discussions with experts in multiple fields of medicine, and to create the first guide for such usage. We reached a consensus with the experts, agreeing that when this principle (structure, quantification, interaction, position: SQIP) is applied to histological observations, the findings will be interpreted correctly. Appropriate use of this recommendation can make human cadaveric studies more accurate and informative. This is the first histology guide for human cadaveric studies.
Dose-dependent reductions in forced expiratory volume over 1 second (FEV 1) and reductions in diffusion lung capacity for carbon monoxide (DL CO) were observed in PONVORY-treated patients mostly occurring in the first month after treatment initiation. In Study 1, the reduction from baseline in percent predicted FEV 1at 2 years was 8.3% in PONVORY-treated patients compared to 4.4% in patients receiving teriflunomide 14 mg. In Study 1, 7 patients discontinued PONVORY because of pulmonary adverse events. There is insufficient information to determine the reversibility of the decrease in FEV 1or FVC after treatment discontinuation. PONVORY should be used with caution in patients with severe respiratory disease (i.e., pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease). Spirometric evaluation of respiratory function should be performed during therapy with PONVORY if clinically indicated.
Participants will receive twice-weekly infusions of midazolam at 0.045mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist.
BACKGROUND: The trend of postponing childbearing age is prevalent worldwide. Advanced paternal age (APA) is associated with adverse pregnancy outcomes and offspring health. However, the underlying mechanism by which paternal aging affects the risk of offspring neuropsychiatric disorders is unclear. Our study aims to explore the behavioral phenotypes and the pathologic epigenetic alterations of APA offspring inherited from aging sperm.
METHODS: Behavioral tests, ELISA assay, immunofluorescence and western blotting were performed on offspring mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA immunoprecipitation sequencing (RIP-seq) were used to investigate the modified N6-methyladenosine (m6A) profiles of paternal sperm and offspring hippocampus. Intervention of gene expression by lentivirus and adeno-associated virus in both vivo and vitro examined the potential therapeutic targets of intergenerational inherited neuroinflammation.
RESULTS: In our study, APA offspring exhibit cognitive impairment and autism-like behavior. An increase in neuroinflammation in APA offspring is associated with microglial overactivation, which manifests as abnormal morphology and augmented engulfment. MeRIP-seq of F0 sperm and F1 hippocampus reveal that Nr4a2 is hypermethylated with decreased expression in APA offspring involving in synaptic plasticity and microglial function. In addition, Ythdc1, an m6A reader protein, is markedly elevated in aging sperm and remains elevated in adult hippocampus of APA group. Enhanced Ythdc1 recognizes and suppresses the hypermethylated Nr4a2, thereby contributing to the abnormal phenotype in offspring. The overexpression of Ythdc1 triggers microglial activation in vitro and its suppression in the hippocampus of APA progeny alleviates behavioral aberrations and attenuates neuroinflammation.
CONCLUSION: Our study provides additional evidence of the abnormal behavioral phenotypes of APA offspring and reveals potential epigenetic inheritance signatures and targeted genes for future research.
DDepending on haematological tolerance (MTD), dose adjustment is proposed if necessary to achieve neutrophils between 1.5 - 3.0 G/L and reticulocytes between 100 - 200 G/L, without exceeding the maximum dose of 35 mg/kg. The titration step is 5 mg/kg except in the case of CrCl ≤ 60 ml/min; 2.5 mg/kg step in this case.
Explicit sensory retraining for lower extremity function (pain, sensory, balance, gait). five one-hour sessions, a week apart: Pre-Post assessment sessions with 3 treatment sessions in between. Home exercise assigned.
OBJECTIVE: Reinforcement learning (RL) is a machine learning technique uniquely effective at sequential decision-making, which makes it potentially relevant to ICU treatment challenges. We set out to systematically review, assess level-of-readiness and meta-analyze the effect of RL on outcomes for critically ill patients.
DATA SOURCES: A systematic search was performed in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection, Elsevier/SCOPUS and the Institute of Electrical and Electronics Engineers Xplore Digital Library from inception to March 25, 2022, with subsequent citation tracking.
DATA EXTRACTION: Journal articles that used an RL technique in an ICU population and reported on patient health-related outcomes were included for full analysis. Conference papers were included for level-of-readiness assessment only. Descriptive statistics, characteristics of the models, outcome compared with clinician's policy and level-of-readiness were collected. RL-health risk of bias and applicability assessment was performed.
DATA SYNTHESIS: A total of 1,033 articles were screened, of which 18 journal articles and 18 conference papers, were included. Thirty of those were prototyping or modeling articles and six were validation articles. All articles reported RL algorithms to outperform clinical decision-making by ICU professionals, but only in retrospective data. The modeling techniques for the state-space, action-space, reward function, RL model training, and evaluation varied widely. The risk of bias was high in all articles, mainly due to the evaluation procedure.
CONCLUSION: In this first systematic review on the application of RL in intensive care medicine we found no studies that demonstrated improved patient outcomes from RL-based technologies. All studies reported that RL-agent policies outperformed clinician policies, but such assessments were all based on retrospective off-policy evaluation.
BACKGROUND AND AIMS: Anesthesiologists prefer ketamine for certain surgeries due to its effectiveness as a non-competitive inhibitor of the N-methyl-D-aspartate receptor in the brain. Recently, this agent has also shown promise as an antidepressant. However, ketamine can cause hallucinogenic effects and is sometimes abused as an illicit drug. Ketamine abuse has been associated with liver and bile duct complications. This systematic study aims to better understand cholangiopathy in ketamine abusers by reviewing case reports.
METHODS AND MATERIAL: In this systematic review, a comprehensive literature search was conducted with the terms "biliary tract diseases" and "ketamine". Case reports and case series of adult patients with documented ketamine abuse and reported cholangiopathy or biliary tract disease were included. We extracted the data of relevant information and the results were reported through narrative synthesis and descriptive statistics.
RESULTS: A total of 48 studies were initially identified, and 11 studies were finally included in the review. The mean age of the patients was 25.88 years. Of the 17 patients, 64.7% were men. Symptoms often included abdominal pain, nausea, and vomiting. Most patients were discharged with improved symptoms and liver function. Common bile duct dilation and other findings were observed in imaging results and other diagnostic studies.
CONCLUSION: This review highlights the diverse presentations and diagnostic modalities used in ketamine-induced cholangiography. These patients tend to be young men with deranged liver function tests and abdominal pain, which should be taken into consideration. These patients often require a multidisciplinary approach in their management.
Continuous intraoperative monitoring with electroencephalo2 graphy (EEG) is commonly used to detect cerebral ischemia in high-risk surgical procedures such as carotid endarterectomy. Machine learning (ML) models that detect ischemia in real time can form the basis of automated intraoperative EEG monitoring. In this study, we describe and compare two time-series aware precision and recall metrics to the classical precision and recall metrics for evaluating the performance of ML models that detect ischemia. We trained six ML models to detect ischemia in intraoperative EEG and evaluated them with the area under the precision-recall curve (AUPRC) using time-series aware and classical approaches to compute precision and recall. The Support Vector Classification (SVC) model performed the best on the time-series aware metrics, while the Light Gradient Boosting Machine (LGBM) model performed the best on the classical metrics. Visual inspection of the probability outputs of the models alongside the actual ischemic periods revealed that the time-series aware AUPRC selected a model more likely to predict ischemia onset in a timely fashion than the model selected by classical AUPRC.
Buprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, postmarketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressant, including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets [see Warnings and Precautions (5.3),Drug Interactions (7)].

Use buprenorphine and naloxone sublingual tablets with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.7)].
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL (see PRECAUTIONS). 

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and PRECAUTIONS). 

If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS).
The invention belongs to the field of traditional Chinese medicines, and concretely relates to a traditional Chinese medicine for treating gynecologic diseases, and a preparation method thereof. The traditional Chinese medicine for treating gynecologic diseases is mainly prepared from, by weight, 30-50 parts of Herba Leonuri, 5-20 parts of Chinese angelica, 5-30 parts of Ligusticum wallichii, 5-15 parts of white peony root and 5-20 parts of licorice root. The preparation method comprises the following steps: drying Herba Leonuri, Chinese angelica, Ligusticum wallichii, white peony root and licorice root, grinding to form powder, and mixing the obtained powder with honey to prepare honeyed pills. The traditional Chinese medicine provided by the invention has the efficacies of tranquillizing mind, calming, regulating menstruation and regulating blood. The traditional Chinese medicinal pill is taken together with a guiding medicine in order to treat and alleviate abnormal leucorrhea, abnormal menstruation, infertility, dystocia, prenatal and postpartum discomfort and other above 80 gynecologic diseases, the cure rate is greater than 90%, and the traditional Chinese medicine has no side effects. The preparation method of the traditional Chinese medicine for treating gynecologic diseases has the advantages of simple process, realization of batch production, and low cost.
For 24 weeks, each participant will measure their blood pressure and respond to questionnaires daily, and visit the institute to provide a blood sample every 4 weeks. The study is split into three 8-week phases, the first of which will start when each participant is enrolled. For the first 8-week observation phase (A1) the participant is instructed to continue with their usual diet and exercise habits. For the second 8-week intervention phase (B), the participant will be provided with wholegrains and nuts and recommended to substitute these in place of refined grains and other snacks, respectively. They will also receive dietary advice for following the Dietary Approaches to Stop Hypertension (DASH) diet. For the final 8 week follow-up period (A2), provision of wholegrains and nuts will cease but the participant will continue with measurements at the same frequency as previously.
This arm will consist of standard care with perineural electrical dry needling, using a high frequency stimulation placed near the nerve, differing from addressing muscular trigger points. For example, a dry needle placed in the semispinalis capitus muscle along the greater occipital nerve pathway, stimulated at 80 Hz.
Acute pancreatitis (AP) is a serious and complex disorder with varying disease course and severity. Early and prompt interventions are crucial in management of AP. Vitamin D, being a prominent actor in calcium metabolism, also takes part in immunity and thus in immune-system related disorders, ranging from infections to cancer. In this study, the role of vitamin D status of a patient on the severity of AP was investigated. This study was conducted between June 2021 to August 2022 with a total of 315 patients. Blood samples were obtained upon admission. A 25-(OH)D3 level less than 10 ng/ml was defined as vitamin D deficiency. 10-19 ng/ml was defined as vitamin D insufficiency whereas 20 ng/ml or above was considered to be sufficient. Scoring systems (Ranson score, CTSI, BISAP, Revised Atlanta Classification (RAC) were applied. Serum 25-(OH)D3 levels of patients with AP were found to be negatively correlated with severity of the disease according to RAC (p < 0.001). In concordance to this finding, both Ranson score and BISAP were found to be statistically significantly related to 25-(OH)D3 levels. Both scoring systems revealed higher scores in patients with insufficient or deficient levels of 25-(OH)D3. Serum 25-(OH)D3 levels were not found to be related to intensive care unit admission or mortality. This study revealed that serum 25-(OH)D3 level is related to the severity of AP. In the future, interventional studies with vitamin D therapy in otherwise serum 25-(OH)D3 deficient AP patients might reveal a new potential therapeutic agent in this mechanically complex, burdensome disorder.
PURPOSE:To provide an aromatic for bath which does not impart its smell to the body of the bathed person, by adsorbing a perfume to a solid carrier at a rate below the absorption capacity of the carrier thereby leaving the remaining capacity of the carrier to absorb water, and using the resultant solid aromatic in combination with an air-permeable bag which can contain said solid aromatic and is resistant to permeation of liquid. CONSTITUTION:The aromatic for bath is composed of a solid aromatic obtained by adsorbing a perfume to a solid carrier (e.g. active alumina, synthetic calcium silicate, etc.), and a container which can contain said solid aromatic and can be floated on water. It is necessary to adsorb the perfume to the solid carrier below the ultimate adsorption capacity, e.g. to the level to leave about 10-50% of the remaining adsorption capacity and to make the carrier to be able to absorb water. When the aromatic is put into a highly humid atmosphere, e.g. in bathtub, the smell of the agent can be increased. The container may have any shape so long as it inhibits the dispersion of the aromatic in water and can be floated stably in water, e.g. a model of a ship, an air-permeable bag having no liquid permeability, etc.
Participants will receive guselkumab 100 milligram (mg) Subcutaneous (SC) injection at Weeks 0, 4, 12, 20, 28, 36, and 44 and placebo SC at Week 24 to maintain the blind. At Week 16, Participants who meet the early escape criteria will receive placebo at Week 16 and guselkumab at Week 20, then guselkumab every 8 weeks (q8w).
BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is a crucial neuromodulation therapy for depression, yet its molecular mechanism remains unclear. Here, we aim to unveil the underlying mechanisms of antidepression by systematically evaluating the change of gene expression in different brain regions (i.e., hippocampus, anterior cingulate cortex, and medial prefrontal cortex).
METHODS: The adolescent depression rat model was established by chronic unpredictable mild stress (CUMS), followed by the taVNS treatment for 3 weeks. The open field test (OFT), forced swimming test (FST), elevated plus maze test (EPM), and new object recognition (NOR) test were used to evaluate depressive- and anxiety-like behaviors. Gene expression analysis of three brain regions was conducted by RNA sequencing (RNA-seq) and further bioinformatics methods.
RESULTS: The depressive- and anxiety-like behaviors in CUMS-exposed rats were manifested by decreased spontaneous locomotor activity of OFT, increased immobility time of FST, increased entries and time in the closed arms of EPM, and decreased new object index of NOR. Furthermore, CUMS exposure also led to alterations in gene expression within the hippocampus (HIP), anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC), suggesting a potential link between adolescent stress and pathological changes within these brain regions. TaVNS could significantly ameliorate depressive- and anxiety-like behaviors. Its effects on these three brain regions were found related to regulation of the metabolism, and there were some brain region-specific findings. Compared with ACC and mPFC, taVNS has a more concrete effect on HIP by regulating the inflammation response and glycolysis.
CONCLUSION: taVNS is capable of ameliorating adolescent depressive- and anxiety-like behaviors by regulating plenty of genes in the three brain regions. Suppressed level of inflammatory response and enhanced glycolysis manifests the dominant role of taVNS in HIP, which provides a theoretical foundation and data support for the molecular mechanism of antidepression by taVNS.
The aim of this study is to investigate the effect of fresh corneal lenticule implantation as allogenic implant that will be taken from myopic patients to implant in hyperopic patients with high astigmatism using VisuMax Femtosecond Laser-Smile module surgery with primary objective to assess(increase) visual acuity (far, intermediate, near vision) and secondary objective to stabilize(decrease) high astigmatism by reducing K values. Fresh corneal lenticule implantation as allogenic implant that we took from myopic patients (-5.0D) to implant in hyperopic patients (+4.0 D +3.0cyl) according to high K2 values. The stromal pocket diameter was 8 mm, 4mm super incision and 130-µm cap thickness.