anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves.
AIM OF THE STUDY: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications.
MATERIALS AND METHODS: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites.
RESULTS: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers.
CONCLUSION: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.
Cotadutide is a dual glucagon-like peptide-1 (GLP-1)/glucagon receptor agonist. Gastrointestinal adverse effects are known to be associated with GLP-1 receptor agonism and can be mitigated through tolerance development via a gradual up-titration. This analysis aimed to characterize the relationship between exposure and nausea incidence and to optimize titration schemes. The model was developed with pooled data from cotadutide-administrated studies. Three different modeling approaches, proportional odds (PO), discrete-time Markov, and two-stage discrete-time Markov models, were employed to characterize the exposure-nausea relationship. The severity of nausea was modeled as different states (non-nausea, mild, and moderate/severe). The most appropriate model was selected to perform the covariate analysis, and the final covariate model was used to simulate the nausea event rates for various titration scenarios. The two Markov models demonstrated comparable performance and were better than the PO model. The covariate analysis was conducted with the standard Markov model for operational simplification and identified disease indications (NASH, obesity) and sex as covariates on Markov parameters. The simulations indicated that the biweekly titration with twofold dose escalation is superior to other titration schemes with a relatively low predicted nausea event rate at 600 μg (25%) and a shorter titration interval (8 weeks) to reach the therapeutic dose. The model can be utilized to optimize starting dose and titration schemes for other therapeutics in clinical trials to achieve an optimal risk-benefit balance and reach the therapeutic dose with minimal titration steps.
The impairment of episodic memory in marijuana abusers has important treatment implications. Since many treatments, including cognitive-behavioral therapy, strongly utilize episodic memory, marijuana use during treatment may lead to diminished treatment outcomes. In addition, lessened response inhibition may lead to elevated rates of drug relapse while in treatment. Consequently, a treatment which will improve episodic memory and response inhibition may lead to improved treatment outcomes in marijuana users. One such treatment is modafinil.This study will be a 4 session within-subjects, double-blind, crossover study evaluating the impact of modafinil (400 mg/day) on the cognitive, subjective, and physiological effects of marijuana. Across 4 sessions, subjects will be randomly assigned to receive either oral placebo, modafinil (400mg), dronabinol (15mg), or dronabinol and modafinil. Outcome measures will include physiological, cognitive, and subjective drug effects.

Currently this study complete and has been published.
A nutrient fiber matrix and associated methods that help control blood sugar levels is described. The matrix can control blood sugar in a variety of ways. In one possible example, the matrix blocks carbohydrates in a manner that reduces the body's ability to take the carbohydrates into its cells. In another example, the matrix acts to increase a person's energy level and feelings of satiety. Thus, the matrix can reduce the person's desire to consume more food and, thereby, help the person to keep from increasing his or her blood sugar levels by eating more. In still another example, the fiber matrix helps sugars to be absorbed over a longer period of time so as to smooth out and prevent spikes in blood sugar levels.
The costimulatory receptor CD137 (also known as TNFRSF9 or 4-1BB) sustains effective cytotoxic T-cell responses. Agonistic anti-CD137 cancer immunotherapies are being investigated in clinical trials. Development of the first-generation CD137-agonist monotherapies utomilumab and urelumab was unsuccessful due to low antitumor efficacy mediated by the epitope recognized on CD137 or hepatotoxicity mediated by Fcγ receptors (FcγR) ligand-dependent CD137 activation, respectively. M9657 was engineered as a tetravalent bispecific antibody (mAb2) in a human IgG1 backbone with LALA mutations to reduce binding to FCγRs. Here, we report that M9657 selectively binds to mesothelin (MSLN) and CD137 with similar affinity in humans and cynomolgus monkeys. In a cellular functional assay, M9657 enhanced CD8+ T cell-mediated cytotoxicity and cytokine release in the presence of tumor cells, which was dependent on both MSLN expression and T-cell receptor/CD3 activation. Both FS122m, a murine surrogate with the same protein structure as M9657, and chimeric M9657, a modified M9657 antibody with the Fab portion replaced with an anti-murine MSLN motif, demonstrated in vivo antitumor efficacy against various tumors in wild-type and human CD137 knock-in mice, and this was accompanied by activated CD8+ T-cell infiltration in the tumor microenvironment. The antitumor immunity of M9657 and FS122m depended on MSLN expression density and the mAb2 structure. Compared with 3H3, a murine surrogate of urelumab, FS122m and chimeric M9657 displayed significantly lower on-target/off-tumor toxicity. Taken together, M9657 exhibits a promising profile for development as a tumor-targeting immune agonist with potent anticancer activity without systemic immune activation and associated hepatotoxicity.
Activity-related dyspnea in chronic lung disease is centrally related to dynamic (dyn) inspiratory constraints to tidal volume expansion. Lack of reference values for exertional inspiratory reserve (IR) has limited the yield of cardiopulmonary exercise testing in exposing the underpinnings of this disabling symptom. One hundred fifty apparently healthy subjects (82 males) aged 40-85 underwent incremental cycle ergometry. Based on exercise inspiratory capacity (ICdyn), we generated centile-based reference values for the following metrics of IR as a function of absolute ventilation: IRdyn1 ([1-(tidal volume/ICdyn)] x 100) and IRdyn2 ([1-(end-inspiratory lung volume/total lung capacity] x 100). IRdyn1 and IRdyn2 standards were typically lower in females and older subjects (p<0.05 for sex and age versus ventilation interactions). Low IRdyn1 and IRdyn2 significantly predicted the burden of exertional dyspnea in both sexes (p<0.01). Using these sex and age-adjusted limits of reference, the clinician can adequately judge the presence and severity of abnormally low inspiratory reserves in dyspneic subjects undergoing cardiopulmonary exercise testing.
Advancements in monitoring technology not only permit the accurate capture of sophisticated physical activity information but also enable the provision of bespoke multidimensional feedback. Personalised feedback, self-monitoring and goal-setting are techniques that have been shown to be very effective in supporting a change in behaviour through improved motivation and awareness. To date the feedback provided in physical activity interventions invariably focuses on just one aspect of the behaviour and has had mixed results. Pedometers for example with a sole focus on the number of steps one takes has been shown to be a reasonably effective form of instant feedback in the short-term but its effects are rarely sustained after the device is removed. Tailored information about the achievement of 30 minutes of moderate to vigorous intensity activity is also only partially effective. One of the reasons might be that in focusing on just one aspect becomes prescriptive and doesn't allow individuals to explore the other important aspects that might be more aligned to their interests, needs and preferences. Having such narrow focused goals and information would likely frustrate rather than support an individual's needs for autonomy and competence, which is thought to be crucial in the adoption and maintenance of a new behaviour.

In this research, we want to find out whether the provision of both instantaneous and multidimensional personalised feedback about the different health-harnessing aspects of physical activity is effective in supporting adults in making a meaningful change to their physical activity behaviour. The study will take a mixed methods approach which will involve two phases. Phase 1 will involve a 2 group randomised control trial that will examine the use of combined instantaneous and multidimensional feedback over a 6-week period with a further follow-up outcome assessment a further 6-weeks after the intervention has finished. The second phase will involve a short one-to-one semi structured interview with each intervention participant that will be designed to qualitatively explore the preferred features of the intervention that were most effective for motivating and supporting a change in behaviour and/or to understand why it wasn't effective if applicable. The qualitative interviews will take place after the 6-week follow-up assessments have been completed so not to influence the results of any outcome measures.
A patient parameter communication hub includes a plurality of patient-parameter-connectors, a data conversion unit, a medical-analysis station connector, and a data-network connector. The plurality of patient-parameter-connectors are adapted for receiving physiological parameter data in a first format. The physiological parameter data are generated by one or more physiological parameter data generators. The data conversion unit is adapted for converting the received physiological parameter data from the first format to a second format. The medical-analysis station connector is adapted for transmitting the received physiological parameter data in the second format to a medical-analysis station for processing and for receiving processed physiological parameter data in the second format from the medical-analysis station. The data-network connector adapted for transmitting the received processed physiological parameter data in the second format over a data-network to one or more destinations. Related apparatus, systems, techniques, and articles are also described.
RESUSCITATIVE EQUIPMENT AND DRUGS SHOULD BE IMMEDIATELY AVAILABLE. (See ADVERSE REACTIONS).

Reactions resulting in fatality have occurred on rare occasions with the use of local anesthetics, even in the absence of a history of hypersensitivity.

Fatalities may occur with use of local anesthetics in the head and neck region as the result of retrograde arterial flow to vital CNS areas even when maximum recommended doses are observed. The practitioner should be alert to early evidence of alteration in sensorium or vital signs.

The solution which contains a vasoconstrictor (CARBOCAINE) should be used with extreme caution for patients whose medical history and physical evaluation suggest the existence of hypertension, arteriosclerotic heart disease, cerebral vascular insufficiency, heart block, thyrotoxicosis and diabetes, etc.

The solution which contains a vasoconstrictor (CARBOCAINE) also contains potassium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people. CARBOCAINE is SULFITE FREE.

CARBOCAINE, along with other local anesthetics, is capable of producing methemoglobinemia. The clinical signs of methemoglobinemia are cyanosis of the nail beds and lips, fatigue and weakness. If methemoglobinemia does not respond to administration of oxygen, administration of methylene blue intravenously 1-2 mg/kg body weight over a 5 minute period is recommended.

The American Heart Association has made the following recommendations regarding the use of local anesthetics with vasoconstrictors in patients with ischemic heart disease: "Vasoconstrictor agents should be used in local anesthesia solutions during dental practice only when it is clear that the procedure will be shortened or the analgesia rendered more profound. When a vasoconstrictor is indicated, extreme care should be taken to avoid intravascular injection. The minimum possible amount of vasoconstrictor should be used." (Kaplan, EL. editor: Cardiovascular disease in dental practice, Dallas 1986, American Heart Association).
The safety and effectiveness of gadobutrol injection have been established in pediatric patients, including term neonates, for use with MRI to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system and for use in MRA to evaluate known or suspected supra-aortic or renal artery disease. Use of gadobutrol injection in these indications is supported by adequate and well-controlled studies in adults and supportive imaging data in two studies in 135 patients 2 to less than 18 years of age and 44 patients less than 2 years of age with CNS and non-CNS lesions, and pharmacokinetic data in 130 patients 2 to less than 18 years of age and 43 patients less than 2 years of age, including term neonates [see Clinical Pharmacology ( 12.3) and Clinical Studies ( 14.1)] . The frequency, type, and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults [see Adverse Reactions ( 6.1)] . No dose adjustment according to age is necessary in pediatric patients [see Dosage and Administration ( 2.1), Clinical Pharmacology ( 12.3), and Clinical Studies ( 14.1)] . The safety and effectiveness of gadobutrol injection have not been established in preterm neonates for any indication or in pediatric patients of any age for use with MRI to assess the presence and extent of malignant breast disease, or for use in CMRI to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (CAD). 

###  NSF Risk

No case of NSF associated with gadobutrol injection or any other GBCA has been identified in pediatric patients ages 6 years and younger. Pharmacokinetic studies suggest that clearance of gadobutrol injection is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. No increased risk factor for NSF has been identified in juvenile animal studies of gadobutrol. Normal estimated GFR (eGFR) is around 30 mL/min/1.73m 2at birth and increases to mature levels around 1 year of age, reflecting growth in both glomerular function and relative body surface area. Clinical studies in pediatric patients younger than 1 year of age have been conducted in patients with the following minimum eGFR: 31 mL/min/1.73m 2(age 2 to 7 days), 38 mL/min/1.73m 2(age 8 to 28 days), 62 mL/min/1.73m 2(age 1 to 6 months), and 83 mL/min/1.73m 2(age 6 to 12 months). 

###  Juvenile Animal Data

Single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants.
INTRODUCTION: Anal fissure (AF) poses a common challenge in clinical practice, prompting various treatment approaches. This multicenter study, conducted by the Italian Society of Colorectal Surgery, aimed to assess treatment trends in AF over a 10 year period.
METHODS: A survey of proctologists and retrospective analysis of patient records were conducted to evaluate treatment modalities and outcomes across six different clinical scenarios based on AF presentation (acute/chronic) stratified by sphincter function (normal/hypertonic/hypotonic).
RESULTS: Analysis of data from 17 principal investigators and 22,016 patients revealed significant variability in treatment approaches, influenced by factors such as symptom duration, anal tone, and surgeon preference. Conservative treatments were commonly utilized, while surgical interventions were reserved for refractory cases. Specifically, pharmaceutical treatment was administered to 66-75% of patients in cases of acute AF and 63-67% for chronic AF, while 10-15% underwent anal dilation, and < 2% received botulinum toxin injection. Among medical treatments, nifedipine with lidocaine and glycerin film-forming ointments were the most utilized. The most performed surgical techniques were fissurectomy and anoplasty, except for patients with chronic AF and hypertonic sphincter where sphincterotomy prevailed. Trends in treatment utilization varied depending on the clinical scenario, with notable shifts observed over time.
CONCLUSIONS: This study provides insights into the evolving landscape of AF management, highlighting the need for further research to elucidate optimal treatment strategies and improve patient outcomes.
Dialectical Behavior Therapy Skills Group (DBT-SG) in addition to VHA treatment as usual. Group is 24 weekly sessions teaching skills in emotion regulation, distress tolerance, interpersonal effectiveness, and mindfulness.
A system and methods for artificially intelligent medical procedure assessment and intervention are provided. A system may acquire image data from a camera targeting a location where healthcare is administered. The system may receive sensor data from a sensor attached to a care provider during performance of a procedure. The system may generate gesture features based on the sensor data. The system may generate image features based on the image data. The system may determine, based on the image features and a machine learning model, a step identifier for a step in a multi-step surgical procedure. The system may access text descriptive of an instruction to perform the step. The system may display the text on a display accessible to the care provider. The system may determine, based on the gesture information and a second machine learning model, a performance metric that measures performance of the care provider.
PURPOSE: This work introduces updated transcripts, disfluency annotations, and word timings for FluencyBank, which we refer to as FluencyBank Timestamped. This data set will enable the thorough analysis of how speech processing models (such as speech recognition and disfluency detection models) perform when evaluated with typical speech versus speech from people who stutter (PWS).
METHOD: We update the FluencyBank data set, which includes audio recordings from adults who stutter, to explore the robustness of speech processing models. Our update (semi-automated with manual review) includes new transcripts with timestamps and disfluency labels corresponding to each token in the transcript. Our disfluency labels capture typical disfluencies (filled pauses, repetitions, revisions, and partial words), and we explore how speech model performance compares for Switchboard (typical speech) and FluencyBank Timestamped. We present benchmarks for three speech tasks: intended speech recognition, text-based disfluency detection, and audio-based disfluency detection. For the first task, we evaluate how well Whisper performs for intended speech recognition (i.e., transcribing speech without disfluencies). For the next tasks, we evaluate how well a Bidirectional Embedding Representations from Transformers (BERT) text-based model and a Whisper audio-based model perform for disfluency detection. We select these models, BERT and Whisper, as they have shown high accuracies on a broad range of tasks in their language and audio domains, respectively.
RESULTS: For the transcription task, we calculate an intended speech word error rate (isWER) between the model's output and the speaker's intended speech (i.e., speech without disfluencies). We find isWER is comparable between Switchboard and FluencyBank Timestamped, but that Whisper transcribes filled pauses and partial words at higher rates in the latter data set. Within FluencyBank Timestamped, isWER increases with stuttering severity. For the disfluency detection tasks, we find the models detect filled pauses, revisions, and partial words relatively well in FluencyBank Timestamped, but performance drops substantially for repetitions because the models are unable to generalize to the different types of repetitions (e.g., multiple repetitions and sound repetitions) from PWS. We hope that FluencyBank Timestamped will allow researchers to explore closing performance gaps between typical speech and speech from PWS.
CONCLUSIONS: Our analysis shows that there are gaps in speech recognition and disfluency detection performance between typical speech and speech from PWS. We hope that FluencyBank Timestamped will contribute to more advancements in training robust speech processing models.
COVID-19 is an infectious disease caused by SARS-CoV-2; over the course of the disease, a dysregulated immune response leads to excessive inflammation that damages lung parenchyma and compromises its function. One of the cell lineages classically associated with pathological inflammatory processes is mast cells (MCs). MCs and their mediators have been associated with COVID-19; we previously reported the role of carboxypeptidase A3 (CPA3) in severe COVID-19. However, sequelae of SARS-CoV-2 infection have been poorly studied. In patients who successfully resolve the infection, one of the reported sequelae is pulmonary fibrosis (PF). The etiology and exact mechanisms are unknown, and few studies exist. Therefore, the aim of this study was to evaluate whether MCs are associated with PF development after SARS-CoV-2 infection. Our findings demonstrate that during severe cases of SARS-CoV-2 infection, there is an increased amount of CPA3+ MCs in areas with pneumonia, around thrombotic blood vessels, and in fibrotic tissue. Moreover, higher numbers of CPA3-expressing MCs correlate with fibrotic tissue development (r = 0.8323; p = 0.001170). These results suggest that during COVID-19, exacerbated inflammation favors the recruitment or expansion of MCs and CPA3 expression in the lungs, which favors tissue damage and a failure of repair mechanisms, leading to fibrosis.