anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
We will assess the effectiveness of the COVID-19 vaccine in preventing post-vaccine health conditions. To do this, we will employ a target trial emulation design, examining the vaccine's effectiveness from the time it was authorized or approved, specifically for different age groups, up until the most recent available data. We will gather patient data from HealthVerity, including those enrolled in the claims database, and supplement it with information from the state's deidentified vaccine registry. Only patients eligible to receive the vaccine during the study period will be included in the analysis of post-vaccine health conditions. We will compare vaccinated individuals with those eligible for vaccination but not vaccinated, using various statistical methods such as descriptive statistics, incidence rates, hazard ratios, and survival curves.

The second part of our study will use a retrospective cohort design to examine the uptake of the vaccine in specific groups over time. We will identify subjects through two different methods: 1) by analyzing all available dosing records in the Immunization Registry, 2) by using HealthVerity claims data based on specific time periods when the vaccine was available. We will follow these individuals until they receive the vaccine under investigation, leave the study, reach the end of the available data, or pass away. We will assess overall vaccination rates and also analyze the data based on the specific type of prior vaccine dose received.
Invasive candidiasis is an important fungal disease caused by Candida albicans and, increasingly, non-albicans Candida pathogens. Invasive Candida infections originate most frequently from endogenous human reservoirs and are triggered by impaired host defences. Signs and symptoms of invasive candidiasis are non-specific; candidaemia is the most diagnosed manifestation, with disseminated candidiasis affecting single or multiple organs. Diagnosis poses many challenges, and conventional culture techniques are frequently supplemented by non-culture-based assays. The attributable mortality from candidaemia and disseminated infections is ~30%. Fluconazole resistance is a concern for Nakaseomyces glabratus, Candida parapsilosis, and Candida auris and less so in Candida tropicalis infection; acquired echinocandin resistance remains uncommon. The epidemiology of invasive candidiasis varies in different geographical areas and within various patient populations. Risk factors include intensive care unit stay, central venous catheter use, broad-spectrum antibiotics use, abdominal surgery and immune suppression. Early antifungal treatment and central venous catheter removal form the cornerstones to decrease mortality. The landscape of novel therapeutics is growing; however, the application of new drugs requires careful selection of eligible patients as the spectrum of activity is limited to a few fungal species. Unanswered questions and knowledge gaps define future research priorities and a personalized approach to diagnosis and treatment of invasive candidiasis is of paramount importance.
FIELD: veterinary microbiology, biotechnology. SUBSTANCE: strain of bacterium Salmonella dublin = 19 shows morphological, cultural and enzymatic properties that are typical for genus Salmonella. By serological properties the proposed strain is agglutinated with sera: monoreceptor 09 and H-sera P. G. The strain is producer of endotoxins, it has protein structure and nucleotide composition of its DNA (as % GC) - 52.9. The strain is lyzed by salmonellosis polyvalent bacteriophage. In intraperitoneal administration to white mice value LD 50  is 3.2 x 10 6  of live microbe cells. The strain is pathogenic for calves in their infection in the concentration 10 billion microbe cells and in 2 days profuse diarrhea can be noticed and in 3-4 days - death of animal. In the strain culturing the concentration of microbe cells is 40-50 billion by optical turbidity standard and protective effect against infection with virulent strains occurs on 5-7 days. The strain is useful for preparing vaccines, diagnostic preparations against salmonellosis in animals and for preparing hyperimmune curative sera and globulins also. EFFECT: valuable properties of strain. 1 ex
Nonalcoholic fatty liver disease (NAFLD) is the predominant cause of liver pathology. Current evidence highlights plasma proteins as potential therapeutic targets. However, their mechanistic roles in NAFLD remain unclear. This study investigated the involvement of specific plasma proteins and intermediate risk factors in NAFLD progression. Two-sample Mendelian randomization (MR) analysis was conducted to examine the association between plasma proteins and NAFLD. Colocalization analysis determined the shared causal variants between the identified proteins and NAFLD. The MR analysis was applied separately to proteins, risk factors, and NAFLD. Mediator shares were computed by detecting the correlations among these elements. Phenome-wide association studies (phewas) were utilized to assess the safety implications of targeting these proteins. Among 1,834 cis-protein quantitative trait loci (cis-pQTLs), after-FDR correction revealed correlations between the plasma levels of four gene-predicted proteins (CSPG3, CILP2, Apo-E, and GCKR) and NAFLD. Colocalization analysis indicated shared causal variants for CSPG3 and GCKR in NAFLD (posterior probability > 0.8). Out of the 22 risk factors screened for MR analysis, only 8 showed associations with NAFLD (p ≤ 0.05), while 4 linked to CSPG3 and GCKR. The mediator shares for these associations were calculated separately. Additionally, reverse MR analysis was performed on the pQTLs, risk factors, and NAFLD, which exhibited a causal relationship with forward MR analysis. Finally, phewas summarized the potential side effects of associated-targeting proteins, including CSPG3 and GCKR. Our research emphasized the potential therapeutic targets for NAFLD and provided modifiable risk factors for preventing NAFLD.
Bosentan will be started at 62.5mg BD for 4 weeks and then increased to 125mg BD. Sildenafil will be started at 20mg OD and then increased to 20mg TDS if there is no fall in BP. Total duration is of 6 months. No fixed dose combination will be used.
Epidemiologic studies have been conducted examining the relationship between combination oral contraceptives and breast cancer. Norethindrone acetate and ethinyl estradiol tablets were not included in these studies, and the majority of the combination oral contraceptives used by women in these studies have higher doses of estrogen than norethindrone acetate and ethinyl estradiol tablets. These studies suggest that the risk of having breast cancer diagnosed may be slightly increased among current and recent users of combination oral contraceptives; however, these studies do not provide evidence for causation. The observed pattern of increased risk of breast cancer diagnosis may be due to earlier detection of breast cancer in combination oral contraceptive users, the biological effects of combination oral contraceptives, or a combination of reasons. The risk appears to decrease over time after combination oral contraceptive discontinuation, and by 10 years after cessation of combination oral contraceptive use, the additional risk disappears. The risk does not appear to increase with duration of use and no consistent relationships have been found with age at first use or doses studied or type of steroid. Most studies show a similar pattern of risk with combination oral contraceptive use regardless of a woman’s reproductive history or her family breast cancer history. Breast cancers diagnosed in current or previous combination oral contraceptive users tend to be less clinically advanced than in nonusers.

Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is a hormonally-sensitive tumor.

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. A pharmacodynamic interaction study in healthy subjects found that the effects of FYCOMPA on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol [see Clinical Pharmacology (12.3)]. Multiple dosing of FYCOMPA 12 mg per day also enhanced the effects of alcohol to interfere with vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants. Care should be taken when administering FYCOMPA with these agents. Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). Advise patients not to drive or operate machinery until they have gained sufficient experience on FYCOMPA to gauge whether it adversely affects these activities.
Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial signals can be inflammatory but mechanisms are only partially understood. We show that activation of the caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes to host defense against viral infection. In cells lacking CAD, the pro-inflammatory activity of sub-lethal signals was reduced. Experimental activation of CAD caused transient DNA-damage and a pronounced DNA damage response, involving major kinase signaling pathways, NF-κB and cGAS/STING, driving the production of interferon, cytokines/chemokines and attracting neutrophils. The transcriptional response to CAD-activation was reminiscent of the reaction to microbial infection. CAD-deficient cells had a diminished response to viral infection. Influenza virus infected CAD-deficient mice displayed reduced inflammation in lung tissue, higher viral titers and increased weight loss. Thus, CAD links the mitochondrial apoptosis system and cell death caspases to host defense. CAD-driven DNA damage is a physiological element of the inflammatory response to infection.
This open-label, sequential, ascending, multi-dose, Phase 1 study will enroll up to 72 subjects with previously treated advanced solid tumor. Subjects at each dose level will receive KW-2450 orally, once daily for 28 days followed by a 1-week observation period. After completing the 1 week observation period, all subjects will receive KW-2450 on a continuous daily schedule. All doses of KW-2450 will be administered to subjects under overnight fasting conditions.

Dose escalation may proceed once \>= 3 subjects have completed the Day 29 blood sample to evaluate glucose. The safety of each dose level will be established prior to enrollment of subjects in the next dose level. Dose escalation will proceed sequentially with accelerated titration. Once the criteria for completing the accelerated titration are reached, dose escalation will follow a modified Fibonacci schedule. Up to 6 subjects will be enrolled at each dose level. Enrollment will proceed until the maximum tolerated dose (MTD) has been established or the highest dose level (800 mg/day) has been reached.
Bile leakage in abdominal drain after cholecystectomy is reported to close spontaneously without any intervention. The aim of this systematic review was to find out the amount and source of bile leaks that can be closed spontaneously and various factors associated with this closure. A systematic search of PubMed, Google Scholar, and Cochrane under preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines was performed. Ten studies were finally included in the review. Five studies were found from India, two from Pakistan, and one each from Mexico, Nepal, and Romania. Maximum volume of bile reported to close spontaneously was 500 ml per day and took seven days to close. Overall 66.6% cases of bile leaks were laparoscopically operated. Bile leakage in abdominal drain after cholecystectomy up to 500 ml per day closes spontaneously in a week time provided patient has no major ductal injury and peritonitis. Key Words: Bile leakage, Abdominal drain, Endoscopic retrograde cholangiopancreatography.
Participants were administered IV normal saline at volume to match age and weight specific doses of fosaprepitant. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone.
Cosmetic compositions which, when applied to the skin, mask skin imperfections and provide more uniform skin tone are described. The compositions can be formulated to address the needs of users having a specific skin tone. The compositions include one or more pigments (e.g., iron oxides) and may also include reflective particles such as mica coated with iron oxide and/or titanium dioxide. The compositions can be oil-in-water emulsions comprising a discontinuous oil phase dispersed in a continuous aqueous phase. The compositions can also include emollients, one or more skin sheen additives, a film former (e.g., polycyclopentadiene) and isohexadecane. Compositions formulated for lighter skin tones can include one or more sunscreen agents. The compositions can be formulated to have high color transfer resistance. Methods of making the compositions and methods of treatment comprising applying the compositions to the skin are also described.
Group 9. High dose prime PanAd3-RSV given by intra-muscular injection (IM) - high dose boost MVA-RSV given by intra-muscular injection (IM). 6 volunteers, 60-75 years. Interval: 8 weeks.
BACKGROUND: Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown.
METHODS: Summary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases.
RESULTS: LDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (P<0.05/91 = 5.49E-04). Significant pleiotropic SNPs were detected for 11 pairs of correlated conditions/diseases. The corresponding pleiotropic genes were differentially expressed in the brain, nerves, heart, and blood vessels and enriched in gluconeogenesis and drug metabolism, biotransformation, and neurons. Comprehensive causal analyses showed strong causality between hypertension, stroke, and high cholesterol, which drive the development of multiple diseases.
CONCLUSIONS: This study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.
Cyclobenzaprine hydrochloride, USP is a white, crystalline tricyclic amine salt with the empirical formula C 20H 21N•HCl and a molecular weight of 311.9. It has a melting point of 217°C, and a pK a of 8.47 at 25°C. It is freely soluble in water and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon solvents. If aqueous solutions are made alkaline, the free base separates. Cyclobenzaprine hydrochloride, USP is designated chemically as 3-( 5H –dibenzo[ a,d]cyclohepten-5-ylidene)- N, N-dimethyl-1-propanamine hydrochloride, and has the following structural formula: 

Cyclobenzaprine HCl USP, 5 mg is supplied as a 5 mg tablet for oral administration.

Cyclobenzaprine HCl USP, 10 mg is supplied as a 10 mg tablet for oral administration.

Cyclobenzaprine HCl tablets USP, 5 mg contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, colloidal silicon dioxide, magnesium stearate and opadry beige (hypromellose 6cP, titanium dioxide, PEG 400, iron oxide yellow and iron oxide red).

Cyclobenzaprine HCl tablets USP, 10 mg contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, colloidal silicon dioxide, magnesium stearate and opadry yellow (hypromellose 3cp, hypromellose 6cp, titanium dioxide, PEG 400, iron oxide yellow and polysorbate 80).
BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined.
HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT.
METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201.
RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed.
CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles. Later, docetaxel (36 mg/m2) was administered an intravenous infusion, weekly for six weeks followed by a 2-week resting period (8-week cycle).
Excessive dosage of calcitriol induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium should be determined twice weekly. In dialysis patients, a fall in serum alkaline phosphatase levels usually antedates the appearance of hypercalcemia and may be an indication of impending hypercalcemia. An abrupt increase in calcium intake as a result of changes in diet (e.g., increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcemia. 

Should hypercalcemia develop, treatment with calcitriol should be stopped immediately. During periods of hypercalcemia, serum calcium and phosphate levels must be determined daily. When normal levels have been attained, treatment with calcitriol can be continued, at a daily dose of 0.25 mcg lower than that previously used. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated. Calcitriol should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.

Immobilized patients, e.g., those who have undergone surgery, are particularly exposed to the risk of hypercalcemia.

In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While this is usually reversible, it is important in such patients to pay careful attention to those factors which may lead to hypercalcemia. Calcitriol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of the serum calcium. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.

Patients with normal renal function taking calcitriol should avoid dehydration. Adequate fluid intake should be maintained.
We investigated the association between sedentary behavior (SB) and wish to die (WTD; i.e., feeling that one would be better off dead or wishing for one's own death), and the extent to which this can be explained by sleep problems, depression, anxiety, loneliness, perceived stress, and social network in a nationally representative sample of adults aged ≥50 years from Ireland. Cross-sectional data from Wave 1 of the Irish Longitudinal Study on Ageing 2009-2011 were analyzed. WTD was defined as answering affirmatively to the question "In the last month, have you felt that you would rather be dead?" SB was used as a continuous variable (hours/day), and also as a categorical (< or ≥8 h/day) variable. Multivariable logistic regression and mediation analyses were conducted. Data on 8163 adults aged ≥50 years were analyzed [mean (SD) age 63.6 (9.1) years; 48.0% males]. Overall, ≥8 (vs. <8) hours/day of SB was associated with a significant 2.04 (95%CI = 1.50-2.76) times higher odds for WTD, while a 1-h increase in SB per day was associated with 1.11 (95%CI = 1.06-1.16) times higher odds for WTD. Mediation analysis showed that sleep problems, depression, loneliness, perceived stress, and social network explained a modest proportion of the association between SB and WTD (mediated percentage 9.3%-14.8%). The present cross-sectional study found that increasing or higher levels of SB is positively associated with WTD. Addressing the identified potential mediators may reduce WTD among people who are sedentary. However, future longitudinal and intervention studies are needed to make concrete recommendations.