anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting.
METHODS: We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values.
RESULTS: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency.
CONCLUSIONS: Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.
The eligible patients will be randomly assigned to either active (PS128) or identical-appearing placebo capsule in an 1 : 1 ratio. A research assistant who is blind to the status of participants will conduct the randomization allocation. Recruited patients will be randomized in 1:1 ratio, by a computer-generated allocation sequence with blocks of 4. Patients, caregivers, and investigators will be all masked to the assignment. To ensure the concealment of the randomization assignment, active drug and placebo will be provided by coded containers. At the end of the first year, the investigators will temporarily decode the blinded medication to analyze the preliminary results.

Active capsule containing 300 mg of probiotics, equivalent to 3x10\^10 CFU of Lactobacillus plantarum PS128. PS128 and placebo will be manufactured by BENED biomedical and packed by a GMP pharmaceutical manufacture. PS128 or placebo will be provided twice, in the morning and in the afternoon, daily. Because activity and diet may alter composition of gut microbiota, the investigators will ask eligible patients not to change their lifestyle or diet pattern. In addition, though effects of psychotropics on inflammation are still controversial (Baumeister et al. 2016b), medications will be kept unchanged during the intervention period. If kinds of psychotropic were changed because of worsening clinical condition, the patient will be withdrawal from the study. However, if only dose of psychotropics were change, the investigators will record the changes, and the patients will be still kept in the study.
The invention relates to a tetanus-toxin-neutralizing B cell epitope peptide and an application thereof. According to the invention, a tetanus toxin fragment C antigen is constructed fragment-by-fragment with an overlap truncation method. A Western Blot method is adopted; the region of a B cell epitope identified by a monoclonal antibody TT5C4 is screened; and the immunoprotection property of the B cell epitope peptide is identified. The B cell epitope peptide provided by the invention can be used in tetanus peptide vaccine researches. The B cell epitope peptide can be used for preparing specific monoclonal antibodies for diagnosing and preventing tetanus. The B epitope peptide provided by the invention can be used for preparing tetanus vaccines for human or mice, and can be used for developing tetanus-preventing polypeptide medicines.
The cardiac autonomic nervous system (CANS) is intimately connected to the regulation of electrophysiology and arrhythmogenesis in cardiac systems. This work aimed at investigating whether interleukin-10 (IL-10) could effectively modulate CANS and suppress ischemia-induced ventricular arrhythmia (VA) through chronically acting on the cardiac sympathetic ganglion (CSG). Using an adeno-associated virus (AAV), we achieved local chronic overproduction of IL-10 in the CSG, left stellate ganglion (LSG). As a result, in the IL-10 group, we observed a decreased number of tyrosine hydroxylase-positive (TH+) cells in the LSG. IL-10 markedly downregulated the nerve growth factor, synaptophysin, as well as growth-associated protein 43 expression. In vivo, results from ambulatory electrocardiography showed that IL-10 overexpression significantly inhibited the cardiac sympathetic nervous system activity and improved heart rate variability. Meanwhile, we observed decreased LSG function as well as prolonged ventricular effective refractory period and suppressed VA after myocardial infarction (MI) in the IL-10 group. In addition, IL-10 overexpression attenuated inflammation and decreased norepinephrine levels in the myocardium after acute MI. In conclusion, our data suggest that chronic IL-10 overexpression modulates cardiac sympathetic nerve remodeling and suppresses VA induced by MI. Neuromodulation through AAV-mediated IL-10 overexpression may have the characteristics of and advantages as a potential neuroimmunotherapy for preventing MI-induced VAs.
This is an open-label, non-randomized, two-stage, FIH Phase 1 study, utilizing an accelerated dose escalation followed by a traditional 3 + 3 dose escalation algorithm to identify the MTD and/or RP2D of YH004 as a single agent (monotherapy) and in combination with Toripalimab. The first stage of the study is the dose escalation phase (i.e., Phase 1a). The second stage of the study is the dose expansion phase (i.e., Phase 1b). During the study, dose interruption(s) and/or delay(s) may be implemented based on toxicity. Dose modifications are permitted following protocol guidelines. Intra-patient dose escalations will be allowed for the early dose cohorts (single-patient dose groups) in Phase 1a. Patients will be considered evaluable for safety and tolerability if they receive at least one dose of YH004 or Toripalimab at the specified cohort dose. Patients in all parts of the trial will remain on therapy until confirmed disease progression or for 1 year, whichever occurs first. However, patients who are clinically unstable will discontinue following the initial assessment of disease progression.
Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.
BACKGROUND: Cortical visual impairment (CVI) is a verifiable visual dysfunction that cannot be attributed to disorders of the anterior visual pathways or any potentially co-occurring ocular impairment. Given the limited knowledge on the most effective interventions for visual impairment resulting from CVI, this case report provides valuable insights into an example of successful implementation of anti-amblyopia therapy in a patient with CVI.
CASE PRESENTATION: This case report presents a 5-year-old girl with CVI secondary to hypoxic-ischemic injury, resulting in visual impairment, dyspraxia, and abnormal visual evoked potential testing. The girl did not suffer from amblyopia, there was no evidence of relevant refractive errors or strabismus, so visual pathway damage was the cause of her visual deficit. Nevertheless, the patient underwent anti-amblyopia therapy and showed significant improvement in visual acuity after 12 months of treatment. The improvement, resulting from visual stimulation, was due to a good functional recovery by a better usage of the damaged visual pathways. The therapy included prescribing corrective glasses and implementing secondary occlusion of the better eye for 4 months, which was protracted for another 4 months, leading to further improvements in visual acuity.
CONCLUSIONS: The case report shows that addressing even minor refractive errors and implementing anti-amblyopia therapy can significantly improve vision in children with CVI, even without co-existing amblyopia. It also highlights the importance of early intervention and multidisciplinary rehabilitation in children with CVI, focusing on motor and cognitive skills. Additionally, it emphasizes the need for further research to establish evidence-based practice standards for improving vision in children with CVI.
The present invention provides methods of site-specifically integrating a polynucleotide sequence of interest in a genome of a eucaryotic cell, as well as, enzymes, polypeptides, and a variety of vector constructs useful therefore. In the method, a targeting construct comprises, for example, (i) a first recombination site and a polynucleotide sequence of interest, and (ii) a site-specific recombinase, which are introduced into the cell. The genome of the cell comprises a second recombination site. Recombination between the first and second recombination sites is facilitated by the site-specific recombinase. The invention describes compositions, vectors, and methods of use thereof, for the generation of transgenic cells, tissues, plants, and animals. The compositions, vectors, and methods of the present invention are also useful in gene therapy techniques.
A method for use in a computer system is provided that links a patient with patient-related data that is displayed on a graphical user interface. The method includes first determining if a digital watermark is required. If a digital watermark is required, the current background color for the display of patient-related data is obtained, along with an intensity value. The subject matter for the watermark is also obtained. The color of the digital watermark is calculated, based upon the obtained background color and intensity value. The digital watermark is then rendered on the display.
Each participant will participate in 4 sessions. During each session, participants will first complete a 10-puff product use period with the ECIG assigned for that session, then a 30-minute ad lib product use period, and then a cigarette/e-cigarette challenge paradigm.
This is a Phase II trial designed to assess the safety, reactogenicity and immunogenicity of one or two doses of monovalent inactivated split influenza 2013 and 2017 A/H7N9 virus vaccines (2013 and 2017 A/H7N9 IIVs) administered intramuscularly at different dosages (3.75 or 15 mcg of hemagglutinin (HA) per dose), given with or without AS03 adjuvant, using different heterologous and homologous prime-boost vaccination schedules. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. This trial will enroll up to 180 males and non-pregnant females, 19 to 50 years of age, inclusive, who are in good health and meet all eligibility criteria and who are influenza A/H7 vaccine/infection naïve by medical history. Subjects will be randomly assigned to 1 of 6 treatment arms (30 subjects per arm) evaluating the interval between the priming (first) and boosting (second) doses and the presence of the adjuvant in the priming (first) and boosting (second) doses. The neuraminidase-specific antibody response and the neuraminidase content of the Inactivated Influenza Virus Vaccine will be determined using tests that are currently under development. Study duration is approximately 22 months with subject participation duration of approximately 18 months. The primary objectives of the study are: 1) to assess the safety and reactogenicity of 2013 and 2017 A/H7N9 IIVs given with or without AS03 adjuvant following receipt of each study vaccine; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of the second study vaccine. The secondary objectives are: 1) to assess unsolicited non-serious adverse events (AEs) following receipt of each study vaccine; 2) to assess medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs), following receipt of each study vaccine; 3) to assess the kinetics and durability of serum HAI and Neut antibody responses following receipt of each study vaccine.
The invention provides clopidogrel hydrogen sulfate compound salts. The salts are prepared through the following steps that: clopidogrel sulfate and a MOR compound are mixed according to a molar ratio of 1:1 or 1:0.5 in a polar solvent (or clopidogrel and a hydrogen sulfate are mixed according to a molar ratio of 1:1); after the reaction finishes, the mixed solution is concentrated, added with polar or nonpolar solvent for crystallization and filtered; and solid obtained is dried and the clopidogrel hydrogen sulfate compound salt is obtained. The molecular structure of the clopidogrel hydrogen sulfate compound salts contains any one of sodium ions, potassium ions, ammonium ions and cesium ions. The preparation method is reasonable in design and simple in process. The clopidogrel hydrogen sulfate compound salts prepared by the method have the characteristics of good stability, small irritant to the gastrointestinal tracts and the like. The clopidogrel hydrogen sulfate compound salts have a general structural formula as follow.
Sample of study was calculated as 32 using G\*Power Software (ver. 3.1.9.2) for 80% power and medium effect size (f=0.25) at 95% confidence level in line with the data of Lin et al. Participants were assigned to the experimental and control groups by the stratified block randomization method. The locks were assigned to layers using Microsoft Excel.

The individuals in the experimental group received pelvic floor muscle exercises training from the researcher using the Roy Adaptation Model in addition to routine discharge training. The patients received a PFME training booklet prepared by the researcher. Face-to-face training was given to the individuals in the experimental group on the day before the operation, on the second and third postoperative days, and on the day of discharge. The training continued with phone calls at the first, second and third weeks and the first, second, third, and sixth months after the surgery. Data was collected a day before discharge, first, second, third, and sixth months after the surgery.
The control group will not receive any specific rehabilitation treatment for gait performance and mobility improvement. At any case, the control group will be authorized, at will, to exercise in non-rehabilitative contexts (i.e. swimming, walking, yoga) for 14 weeks. After this period they will receive TOCT as treatment plus a home-exercise maintenance program for 3 months.
NEW MATERIAL:A peptide of formula I (A is H or an organic residue reactive with amino group; pro is is L-proline; phe is L-phenylalanine; B is pro or glycine;  C is OH or organic residue reactive with carboxyl; n is 1 or 2; however, B is pro  when n is 1). EXAMPLE:The compound of formula II (Gly is glycine). USE:An additive for a cosmetic having improved beutifying effect on the skin, e.g. prevention of fine wrinkles and aging of the skin, with high safety without irritant action on the skin, improved cosmetic effects, e.g. adhesiveness to the skin, covering power of the skin surface and feeling of use, and good storage stability. The amount of the additive is 0.001-1wt% in a basic cosmetic material and a base material for a makeup cosemetic. PROCESS:The peptide of formula I is obtained by protecting the amino or carboxylic group which will not participate in the reaction of the corresponding amino acid or peptide, and condensing the protected amino acid or peptide.
The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including fluvoxamine maleate tablets, alone but particularly with concomitant use of serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, meperidine, methadone, lithium, tramadol, tryptophan, buspirone, amphetamines and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular aberrations (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of fluvoxamine maleate tablets with MAOIs intended to treat psychiatric disorders is contraindicated. Fluvoxamine maleate tablets should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking fluvoxamine maleate tablets. Fluvoxamine maleate tablets should be discontinued before initiating treatment with the MAOI [see Contraindications (4), Dosage and Administration (2.4, 2.5)].

If concomitant use of fluvoxamine maleate tablets with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamines and St. John's Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Treatment with fluvoxamine maleate tablets and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.
This systematic review with meta-analysis assessed the effects of adverse childhood experiences (ACEs) linked to overweight or obesity in adolescents. Twenty-eight studies (cross-sectional, case-control, or cohort) were included, which described individuals with a history of ACE or adverse family experiences, such as physical, emotional, or psychological abuses; neglect; exposure to domestic violence or peer violence; and sexual abuse. Body mass index (BMI) or BMI z score was used by the study to define adolescents with overweight or obesity. Adolescents who reported childhood experiences, mainly physical, sexual, and emotional abuses, were more associated with overweight/obesity, especially those who experienced four or more ACEs. Network meta-analysis indicated that physical, sexual, and neglect were the most common ACEs associated with obesity in adolescents. Due to significant differences and imprecision among the studies, network meta-analysis was inconclusive in determining the impact of other types of ACE on outcomes. However, evidence suggests that exposure to sexual and physical abuse, as well as neglect, is associated with adolescents who are obese or overweight, as well as with the number of ACE experienced. The study presented evidence suggesting that dealing with many ACEs may be a risk factor for overweight and obesity in adolescents.
Pulmonary hypertension (PH) affects 60-80% of patients with chronic heart failure (HF) and has a critical impact on prognosis. Currently, there is no specific treatment approved for this indication. Experimental research, performed by members of the consortium, demonstrates that treatment with B3 adrenergic receptor agonists produces a beneficial effect on pulmonary hemodynamics, right ventricular (RV) remodeling and pulmonary vascular proliferation in a translational pig model of postcapillary PH. Mirabegron, an oral B3AR agonist, is currently approved for a different medical condition (overactive bladder syndrome) with a good safety profile. Our main objective is to evaluate the efficacy and safety of mirabegron in patients with PH secondary to HF.

The objective will be evaluated by conducting a phase-2 randomized placebo-controlled clinical trial in patients with PH associated to HF. Patients will be randomized 1:1 to mirabegron or placebo, and dose will be titrated till 200 mg/day. Patients will be evaluated with quality of life questionnaire, blood analysis, ECG, echocardiography, 6-minute walking test, right heart catheterization (RHC) and cardiac magnetic resonance (CMR) at baseline and after 16 weeks of treatment.