anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The genetic basis of nonsyndromic familial nonmedullary thyroid carcinoma (FNMTC) is still poorly understood, as the susceptibility genes identified so far only account for a small percentage of the genetic burden. Recently, germline mutations in DNA repair-related genes have been reported in cases with thyroid cancer. In order to clarify the genetic basis of FNMTC, 94 genes involved in hereditary cancer predisposition, including DNA repair genes, were analyzed in 48 probands from FNMTC families, through targeted next-generation sequencing (NGS). Genetic variants were selected upon bioinformatics analysis and in silico studies. Structural modeling and network analysis were also performed. In silico results of NGS data unveiled likely pathogenic germline variants in 15 families with FNMTC, in genes encoding proteins involved in DNA repair (ATM, CHEK2, ERCC2, BRCA2, ERCC4, FANCA, FANCD2, FANCF, and PALB2) and in the DICER1, FLCN, PTCH1, BUB1B, and RHBDF2 genes. Structural modeling predicted that most missense variants resulted in the disruption of networks of interactions between residues, with implications for local secondary and tertiary structure elements. Functional annotation and network analyses showed that the involved DNA repair proteins functionally interact with each other, within the same DNA repair pathway and across different pathways. MAPK activation was a common event in tumor progression. This study supports that rare germline variants in DNA repair genes may be accountable for FNMTC susceptibility, with potential future utility in patients' clinical management, and reinforces the relevance of DICER1 in disease etiology.
PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases.
METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6KozakGAL4 allele to assess the expression pattern of dYkt6.
RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, developmental delay, and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual is homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] and exhibited neurodevelopmental disorders and optic atrophy. Fly dYkt6 is essential and is expressed in the fat body (analogous to liver) and central nervous system. Wild-type genomic rescue constructs can rescue the lethality and autophagic flux defects, whereas the variants are less efficient in rescuing the phenotypes.
CONCLUSION: The YKT6 variants are partial loss-of-function alleles, and the p.(Tyr185Cys) is more severe than p.(Tyr64Cys).
Prior expectations influence pain experience. These expectations, in turn, rely on prior pain experience, but they may also be socially influenced. Yet, most research has focused on self rather than social expectations about pain, and hardly any studies examined their combined effects on pain. Here, we adopted a Bayesian learning perspective to investigate how explicitly communicated social expectations ('advice about pain tolerance') affect own pain expectations, and ultimately pain tolerance, under varying conditions of social epistemic uncertainty (trustworthiness of the advice). N = 72 female participants took part in a coldpressor (cold water) task before (self-learning baseline) and after (socially-influenced learning) receiving advice about their likely pain tolerance from a confederate, the trustworthiness of whom was experimentally manipulated. We used path analysis to test the hypothesis that social advice from a highly trustworthy confederate would influence participants' expectations about pain more than advice from a less trustworthy source, and that the degree of this social influence would in turn predict pain tolerance. We further used a simplified, Bayesian learning, computational approach for explicit belief updating to examine the role of latent parameters of precision optimisation in how participants subsequently changed their future pain expectations (prospective posterior beliefs) based on the combined effect of the confederate's advice on their own pain expectations, and their own task experience. Results confirmed that participants adjusted their pain expectations towards the confederate's advice more in the high- vs. low-trustworthiness condition, and this advice taking predicted their pain tolerance. Furthermore, the confederate's trustworthiness influenced how participants weighted the confederate's advice in relation to their own expectations and task experience in forming prospective posterior beliefs. When participants received advice from a less trustworthy confederate, their own sensory experience was weighted more highly than their socially-influenced prior expectations. Thus, explicit social advice appears to impact pain by influencing one's own pain expectations, but low social trustworthiness leads to these expectations becoming more malleable to novel, sensory learning.
FIELD: medicine, pharmacy. SUBSTANCE: invention describes a tablet for very rapid and prolonged release of active substances. Tablet comprises two layers applied each on other. The first layer consists of mixture of excipients, one or some loosening agents and the active component. The first layer allows carrying out very rapid release of active substance. The second layer contacts with the first layer and it consists of biologically stable inert porous polymeric matrix where an active substance is dispersed. Tablets are made by granulation method followed by pressing. The preferable used active component is 2-ethoxymethyl-4(3H)-pteridinone. Bilayer tablets retain their kinetic indices of an active substance releasing being without dependence on the usage conditions in vivo. EFFECT: improved and valuable medicinal and pharmaceutical properties of tablet. 11 cl, 6 dwg, 2 tbl, 4 ex
Participants will receive at their home the activity tracker of Fitbit brand, model Inspire HR 2, as well as instructions to download and use the CarpeDiem application and the Fitbit application in their mobile phones and synchronize the bracelet. The intervention consists of detecting unhealthy user behaviors and, through contextualized and personalized recommendations and strategies based on gamification, modifying said behaviors and motivating individuals to maintain this modification over time in order to prevent illnesses associated with bad habits. The intervention is performed through the CarpeDiem application, participants will be able to answer follow-up questionnaires, carry out missions designed to improve their eating habits, monitor their physical activity and sleep.
Septic shock is an important contributor of mortality in the intensive care unit (ICU). The crude mortality is reported to be from 30% to 65% (1-5). Although there are significant advances in the management of septic shock in recent decades, the mortality rate was only marginally reduced. For example, the CUB-Réa Network study reported that the mortality rate of septic shock declined from 62.1% in 1993 to 55.9% in 2000 (6). The well-known Surviving Sepsis Campaign has also made every effort to reduce mortality rate of severe sepsis and septic shock. The organization recommended bundled strategies including early goal directed therapy (EGDT) for the management of septic shock (7,8). Although EGDT was once the mainstay therapy of septic shock, its efficacy has been questioned by recent several large randomized controlled trials (9,10). Therefore, the treatment of septic shock is still a global challenge and there is no well-established intervention that can reduce its mortality.

Anisodamine is an active agent isolated from a Chinese herb medicine. Both experimental and clinical studies have shown some potential beneficial effects of anisodamine in improving outcomes of shock (11-13). It was reported that anisodamine could reduce the mortality rate of fulminant epidemic meningitis from 66.9% to 12.4% (14). The efficacy of anisodamine might be mediated via the inhibition of thromboxane synthesis, granulocyte and platelet aggregation (15). Although anisodamine has been widely used in the treatment of septic shock in mainland China, there is no solid evidence from well designed clinical trials to support its efficacy. The aim of the study is to investigate the effectiveness of anisodamine in the treatment of critically ill patients with septic shock.
Participants (16 overweight women, BMI (Body mass index) ˃25, ages 18- 30 y)will complete a one-month intervention where they will restrict their daily food intake to an 8-hour time period, i.e., between 1200 to 2000 hours. During the remaining 16-hour intermittent fasting period (2000 to 1200 hours) participants will be allowed to drink zero calorie beverages (diet soda pop, black coffee, tea, water, etc) in order to maintain normal hydration. There will be no attempt to restrict food intake. Rather simply to restrict the time period each day when food is consumed. Participants' fat mass will be monitored non-invasively using densitometry (with a Bod Pod) prior to and following a 4 week intervention where the participants will eat their normal daily intake during an 8-hour period each day (1200 to 2000 hours). The Bod Pod measures body volume via air displacement and together with an accurate measure of body mass enables body density to be calculated (Density = mass/volume). Satisfaction, hunger, and fullness with the diet will be monitored on a weekly basis using a validated visual analog scale (Flit et al, 2000). Adherence to the diet will also be assessed on a weekly basis as the number of days the diet was followed. During the 16-hour fasting period participants will be able to drink as much of zero calorie beverages as they desire. On day 2, 7, 14, 21, \& 28 participants will return to the lab at 8am (following a 12 hour fasting period) and both the acidity of their urine (using a urine dip stick) and their blood sugar (using a glucometer) will be tested. Following one month the participants will be allowed either to continue this eating pattern or revert to their prior 3 meal intake. After a month of self-regulation, the participants' fat mass will be measured again using the Bod Pod.
Dual-task performances of healthy individuals with similar demographic characteristics in COPD patients will be compared. For this, the demographic information of healthy volunteers will be recorded, and the Timed Up and Go Test, which will be done as a dual task and a single task, and the 10-meter Walk Test will be evaluated.
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
Dietary Supplement: Milled Seed Mix Intervention arm includes milled mix of flax, sesame and pumpkin seeds (18/6/6 g) in sour milk taken as dietary replacement meal during the day, and between lunch and dinner. Seeds are provided with the same producer at the Belgrade market.
BACKGROUND: T cell exhaustion is a state in which T cells become dysfunctional and is associated with a decreased efficacy of immune checkpoint inhibitors. Lung cancer has the highest mortality among all cancers. However, the roles of genetic variants of the T cell exhaustion-related genes in the prognosis of non-small cell lung cancer (NSCLC) patients has not been reported.
METHODS: We conducted a two-stage multivariable Cox proportional hazards regression analysis with two previous genome-wide association study (GWAS) datasets to explore associations between genetic variants in the T cell exhaustion-related genes and survival of NSCLC patients. We also performed expression quantitative trait loci analysis for functional validation of the identified variants.
RESULTS: Of all the 52,103 single nucleotide polymorphisms (SNPs) in 672 T cell exhaustion-related genes, 1,721 SNPs were found to be associated with overall survival (OS) of 1185 NSCLC patients of the discovery GWAS dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, and 125 of these 1,721 SNPs remained significant after validation in an additional independent replication GWAS dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. In multivariable stepwise Cox model analysis, three independent SNPs (i.e., LRRC8C rs10493829 T>C, OAS2 rs2239193 A>G, and CCL25 rs3136651 T>A) remained significantly associated with OS with hazards ratios (HRs) of 0.86 (95% confidence interval (CI) = 0.77-0.96, P = 0.008), 1.48 (95% CI = 1.18-1.85, P < 0.0001) and 0.78 (95% CI = 0.66-0.91, P = 0.002), respectively. Further combined analysis for these three SNPs suggested that an unfavorable genotype score was associated with a poor OS and disease-specific survival. Expression quantitative trait loci analysis suggested that the LRRC8C rs10493829 C allele was associated with elevated LRRC8C mRNA expression levels in normal lymphoblastoid cells, lung tissue, and whole blood.
CONCLUSION: Our findings suggested that these functional SNPs in the T cell exhaustion-related genes may be prognostic predictors for survival of NSCLC patients, possibly via a mechanism of modulating corresponding gene expression.
In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG.  1 A). The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle.
Patients randomized to the usual care arm will be treated almost the same as if they do not enroll in the study. They will be managed in accordance with best ICU (intensive care unit) practices, with treatment decisions made by the treating team. Often this will include blood draws (often 2 teaspoons once or twice per day, but sometimes exceeding this), assessments of cardiac function, assessments of fluid status, and other measures as dictated by the presenting illness (this is broad and will include antibiotics, diuretics, cardiac medications, ventilator and oxygen management, etc.). Patients in the usual care arm will not have diuresis managed by NICOM.
Forty volunteers will be enrolled in this open label, prospective study to determine the correlation between the tidal volumes measured with the Linshom detector and those measured with the mechanical ventilator. after Institutional Review Board (IRB) approval and written informed consent from the volunteers.

The Linshom detector, which is comprised of two rapid responding medical-grade thermistors in close proximity to the mouth/nose (sensor) and a thermistor remote to the airway, will be mounted in the continuous positive airway pressure (CPAP) face mask to measure the temperature during breathing. The CPAP will be connected to a Servo-I ventilator (Maquet) with a circuit and disposable filter. The volunteers will be instructed to breathe normal through the CPAP mask on room air. The excursions of the thermistor tracings (from valley to peak) will be recorded by the Linshom device and displayed continuously on a laptop monitor in a waveform. The tidal volume will also be measured by the ventilator and the data downloaded in a Compact Flash card. The temperature profiles from the sensors and the relative tidal volume will be correlated with the tidal volumes measured by the ventilator.
In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Examples disclosed herein include a method for securely collecting and managing document data is disclosed. First handwriting data is received from a first user device. Responsive to receiving the first handwriting data, an additional handwriting data security process is initiated. After initiating the additional handwriting data security process, additional handwriting data is received from a second user device. Based on the additional handwriting data security process, the first handwriting data is accepted or rejected. After accepting the first handwriting data, a document is generated with the first handwriting data and the additional handwriting data being applied to the document.
Those patients randomized to receive LIA of EXPAREL will have 266mg EXPAREL diluted to 100mL, and drawn into (5) 20mL syringes affixed with (5) 22-gauge needles. Investigators will administer the syringes to the tissue in small increments with the plunger held steady while withdrawn from the tissue to avoid saturating the area around the needle sticks since EXPAREL doesn't readily travel through the tissue.
Trial design: Two centre open label randomised control trial to evaluate the phased withdrawal versus continuation of heart failure treatment for 'recovered' human epidermal growth factor receptor 2 (HER2) therapy-related cardiac dysfunction in non-high risk patients following completion of HER2 therapy. The trial will include cardiovascular magnetic resonance scans (CMR) with automated in-line analytics to improve the sensitivity for detection of early relapse, and detailed patient questionnaires assessing medication disutility to better understand participant motivations and concerns related to treatment continuation and withdrawal.

Trial population: The trial will recruit 90 adult participants (\>18 years) with a prior diagnosis of HER2-targeted therapy related cardiac dysfunction, who currently receive standard heart failure/ cardioprotective medications (any combination of Angiotensin-converting enzyme \[ACE\] inhibitors, angiotensin receptor blockers \[ARBs\] and/or beta-blockers), and whose cardiac function has 'recovered'. 'Recovery' is defined as absence of heart failure symptoms with left ventricular ejection fraction (LVEF) improved to 50% or greater and N-terminal pro B-type natriuretic peptide (NTproBNP) \<200ng/L, for greater than 6 months. Patients will be recruited from Barts Health and University College London Hospitals (UCLH) cardio-oncology and breast cancer clinics. Exclusion criteria: Patients with advanced/ metastatic HER2 positive breast cancer requiring ongoing HER2 therapies or with life expectancy \<12months will be excluded. Patients classed as high/very high cardiotoxicity risk according to the European Society of Cardiology/International Cardio-Oncology Society Position Statement (Lyon et al, 2020), LVEF \<50% prior to HER2-therapies or on completion of anthracycline treatment, or indications for ongoing ACE inhibitors, ARBs and/or beta-blockers, nor those with absolute contraindications to CMR.

Interventions and Duration of treatment: Participants will undergo phased withdrawal of heart failure/ cardioprotective treatments according to a pre-specified algorithm based on the 'Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy' (TRED-HF) study protocol (Halliday et al 2019). This had been designed following extensive consultation with independent experts and attempts to mimic 'real-world' medication withdrawal in clinical practice. Medications will be down titrated in a phased process every 2 weeks over a maximum of 16 weeks. Drug doses will be reduced by 50% in a stepwise manner every 2 weeks, until the patient is taking 25% or less of the maximum recommended dose at which point the medication will be stopped. Monitoring with fortnightly virtual consultations will confirm drug dose reduction and provide support. Participants will undergo clinical assessment at 6, 14 and 24 weeks and 6, 9 and 12 months with weight, blood pressure, and biomarker measurement. At baseline, 6- and 12-month visits detailed cardiovascular phenotyping using CMR and symptom and disutility questionnaires will be undertaken.
The invention provides a method for preparing sheet-shaped powders or casting cosmetics, wherein various cosmetics are made into powder slurry by compounds, that is semiliquid. A pre-molded container (1) is prepared. The container (1) is equipped with separators (2). The height of the separating partition (2) is smaller than the total depth of the container (1). Then the compounds (4) for cosmetics are poured into the space between adjacent containers (1). The space is defined between the above separators (2). The casting is preformed in the above way, so that at least one of the compounds exceeds all the separators (2) of the container (1). By adopting the method, the casting compound is continuously solidified until a unique cosmetic (6) is formed by the compound with its adjacent tablet. The adjacent tablet (4) corresponds with a different casting compound. The unique solidified cosmetic (6) is taken out of the container (1) and then is inserted into a final packaging. The inner separators (2) of the container (1) can be permanently or movably fixed to the bottom of the container (1).
The invention discloses a medicament for treating infertility and a preparation method thereof. The medicament is characterized by being prepared by uniformly mixing up 21 Chinese medicinal materials, namely, radix bupleuri, radix curcumae, codonopsis pilosula, angelica sinensis, radix paeoniae alba, rhizoma cyperi and the like, adding water and boiling for 2-4 times for 1-2 hours each time, combining the boiled liquids, filtering, concentrating the filtrate into clear paste with relative density of 1.15-1.18 at 70 DEG C, refrigerating and standing, filtering the supernate, adding ordinary auxiliaries into the filtrate, uniformly mixing up, adding purified water till the crude medicine content is 1g/ml, filling, sealing up, sterilizing and preparing into an oral liquid preparation. The medicament has the functions of tonifying kidney essence by soothing the liver, eliminating kidney stasis and tonifying the spleen. People say that kidney breeds essence and is mainly responsible for reproduction, the kidney energy is rich, the sexual function is mature, main arteries and veins are smooth, menses occurs, sperms and eggs are combined, and then pregnancy is realized; the liver, the spleen and the kidney are mutually prompted and balanced, a good internal environment is created for pregnancy, the rate and the development in pregnancy are prompted, and the infertility suffering of patients for years is solved. The medicament is low in cost, convenient to take and free of toxic and side effects. The effect is good when the medicament is applied to infertility treatment.
The placebo arm will receive placebo pills identical in appearance to prednisone 10mg pills. They will start taking them 7 days prior to surgery with a taper (4 tabs/day for 3 days, 3 tabs/day for 3 days, 2 tabs/day for 3 days, 1 tab/day for 3 days).