anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Captopril and hydrochlorothiazide tablets, USP for oral administration combines two antihypertensive agents: captopril and hydrochlorothiazide. Catopril, the first of a new class of antihypertensive agents, is a specific competitive inhibitor of angiotensin I-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I to angiotensin II. Hydrochlorothiazide is a benzothiadiazide (thiazide) diuretic-antihypertensive.

Captopril, USP is a white to off-white crystalline powder that may have a slight sulfurous odor; it is soluble in water (approx. 160 mg/mL), methanol, and ethanol and sparingly soluble in chloroform and ethyl acetate.

Hydrochlorothiazide, USP is a white crystalline powder slightly soluble in water but freely soluble in sodium hydroxide solution.

Captopril is designated chemically as 1-[(2S)-3-Mercapto-2-methylpropionyl]-L-proline; Hydrochlorothiazide is 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Their structural formulas are:

Captopril and Hydrochlorothiazide Tablets, USP are available for oral administration in four combinations of captopril with hydrochlorothiazide: 25 mg with 15 mg, 25 mg with 25 mg, 50 mg with 15 mg, and 50 mg with 25 mg. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium lauryl sulfate. The 25 mg/25 mg and 50 mg/25 mg tablets also contain the coloring agent FD&C Yellow #6 Aluminum Lake.
Doxazosin is a quinazoline compound that is a selective inhibitor of the alpha1 subtype of alpha-adrenergic receptors. The chemical name of Doxazosin is 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl) piperazine methanesulfonate. The empirical formula for Doxazosin is C23H25N5O5 ∙ CH4O3S and the molecular weight is 547.6. It has the following structure:

Doxazosin is freely soluble in dimethylsulfoxide, soluble in dimethylformamide, slightly soluble in methanol, ethanol, and water (0.8% at 25°C), and very slightly soluble in acetone and methylene chloride. Doxazosin tablet is available as colored tablets for oral use and contains doxazosin mesylate equivalent to 1 mg (white), 2 mg (yellow or white), 4 mg (orange or white) and 8 mg (green or white) of doxazosin as the free base.

The inactive ingredients for all tablets are microcrystalline cellulose, lactose, sodium starch glycolate, magnesium stearate and sodium lauryl sulfate. The 2 mg yellow tablet contains D & C yellow 10 and FD & C yellow 6; the 4 mg orange tablet contains FD & C yellow 6; the 8 mg green tablet contains FD & C blue 2 and D & C yellow 10.
Patients receive gemcitabine/nab-paclitaxel combination chemotherapy on days 1, 8 and 15, and telotristat ethyl PO QD, BID, or TID on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Human cytokine mixtures produced by cytokine regulatory factor-overexpressing cells and methods of production are disclosed. The mixtures are prepared by culturing human cytokine-producing cells under conditions of cytokine regulatory factor overexpression, treating the cells to induce cytokine production, and isolating the mixtures of cytokines produced by the cells.  Preferred compositions, for use in treating viral infection or cancer, include a mixture of human interferon .gamma. and either human interferon .alpha. or human interferon .beta., in a mole ratio of between 1:1 to 1:100 interferon .gamma. to interferon .alpha. or human interferon .beta..
Microscopy methods for determining embryo viability are described. A method can include accessing, at a compute device, fluorescence lifetime imaging microscopy (FLIM) data set associated with a biological material. The biological material can include either an embryo or a gamete. The method further includes extracting a fluorescence photon arrival time from a subset of data from the FLIM data set. The method further includes estimating a likelihood that the biological material will produce a successful pregnancy and/or a live birth based on the fluorescence photon arrival time histogram and an estimation model that has been trained using artificial intelligence and labeled clinical training data. The method includes generating an output signal representing the estimated likelihood that the biological material will produce a successful pregnancy and/or a live birth. In some embodiments, the method can include training the estimation model using a plurality of fluorescence photon arrival time histograms of the FLIM data set.
South Asians (SAs) develop type 2 diabetes at lower body mass index values than white Europeans (WEs). This basic human experimental study aimed to compare the metabolic consequences of weight gain in SA and WE men without overweight or obesity. Fourteen SAs and 21 WEs had assessments of body composition, metabolic responses to mixed-meal ingestion, cardiorespiratory fitness and physical activity, and a subcutaneous abdominal adipose tissue biopsy, before and after 4-6 weeks of overfeeding to induce 5-7% weight gain. Here we show that body mass index and whole-body adipose tissue volume increases similarly between ethnic groups, but SAs gain less lean tissue. SAs experience a substantially greater decrease in insulin sensitivity compared with WEs (38% versus 7% decrease, P = 0.009), have fewer small (37.1% versus 60.0%, P = 0.003) and more large (26.2% versus 9.1%, P = 0.005) adipocytes at baseline and have a smaller decrease in very small adipocytes with weight gain (-0.1% versus -1.9%, P < 0.0001). Ethnic differences in adipocyte morphology are associated with SA's greater adverse metabolic changes with weight gain. ClinicalTrials.gov registration: NCT02399423 .
BACKGROUND AND PURPOSE: Blood-based biomarkers are a non-invasive solution to predict the risk of conversion of mild cognitive impairment (MCI) to dementia. The utility of free plasma amyloid peptides (not bound to plasma proteins and/or cells) as an early indicator of conversion to dementia is still debated, as the results of studies have been contradictory. In this context, we investigated whether plasma levels of the free amyloid peptides Aβ1-42 and Aβ1-40 and the free plasma Aβ1-42/Aβ1-40 ratio are associated with the conversion of MCI to dementia, in particular AD, over three years of follow-up in a subgroup of the BALTAZAR cohort. We also compared their predictive value to that of total plasma Aβ1-42 and Aβ1-40 levels and the total plasma Aβ1-42/Aβ1-40 ratio.
METHODS: The plasma Aβ1-42 and Aβ1-40 peptide assay was performed using the INNO-BIA kit (Fujirebio Europe). Free amyloid levels (defined by the amyloid fraction directly accessible to antibodies of the assay) were obtained with the undiluted plasma, whereas total amyloid levels were obtained after the dilution of plasma (1/3) with a denaturing buffer. Free and total Aβ1-42 and Aβ1-40 levels were measured at inclusion for a subgroup of participants (N = 106) with mild cognitive impairment (MCI) from the BALTAZAR study (a large-scale longitudinal multicenter cohort with a three-year follow-up). Associations between conversion and the free/total plasma Aβ1-42 and Aβ1-40 levels and Aβ1-42/Aβ1-40 ratio were analyzed using logistic and Cox Proportional Hazards models. Demographic, clinical, cognitive (MMSE, ADL and IADL), APOE, and MRI characteristics (relative hippocampal volume) were compared using non-parametric (Mann-Whitney) or parametric (Student) tests for quantitative variables and Chi-square or Fisher exact tests for qualitative variables.
RESULTS: The risk of conversion to dementia was lower for patients in the highest quartile of free plasma Aβ1-42/Aβ1-40 (≥ 25.8%) than those in the three lower quartiles: hazard ratio = 0.36 (95% confidence interval [0.15-0.87]), after adjustment for age, sex, education, and APOE ε4 (p-value = 0.022). This was comparable to the risk of conversion in the highest quartile of total plasma Aβ1-42/Aβ1-40: hazard ratio = 0.37 (95% confidence interval [0.16-0.89], p-value = 0.027). However, while patients in the highest quartile of total plasma Aβ1-42/Aβ1-40 showed higher MMSE scores and a higher hippocampal volume than patients in the three lowest quartiles of total plasma Aβ1-42/Aβ1-40, as well as normal CSF biomarker levels, the patients in the highest quartile of free plasma Aβ1-42/Aβ1-40 did not show any significant differences in MMSE scores, hippocampal volume, or CSF biomarker levels relative to the three lowest quartiles of free plasma Aβ1-42/Aβ1-40.
CONCLUSION: The free plasma Aβ1-42/Aβ1-40 ratio is associated with a risk of conversion from MCI to dementia within three years, with performance comparable to that of the total plasma Aβ1-42/Aβ1-40 ratio. Threshold levels of the free and total plasma Aβ1-42/Aβ1-40 ratio could be determined, with a 60% lower risk of conversion for patients above the threshold than those below.
Doberman Pinschers are known for their increased susceptibility to dilated cardiomyopathy (DCM) relative to other domestic dogs. This makes the Doberman Pinscher a key model for gene-disease investigations. We conducted a genome-wide association study (GWAS) leveraging a database of genetic profiles obtained through collaboration with the Doberman Diversity Project (DDP). We worked in parallel to increase the depth and power of the DDP database. We exchanged direct correspondences with listed breeders and owners to establish health updates for participant dogs. In total, our study included data on 216, 184 single nucleotide polymorphisms (SNPs) in 46 cases and 3226 population control Doberman Pinschers. Using a generalized linear mixed model and saddlepoint approximation to correct for unbalanced group sizes, we identified a cluster of SNPs associated with DCM on chromosome 16.
A sequence in the coat glycoprotein of rabies virus is identified as the molecular basis for an essential step in the pathogenesis of the virus, the binding of virus to acetylcholine receptor at neuromuscular junctions prior to virus uptake into peripheral nerves. Based on this discovery, synthetic peptide-based, anti-rabies vaccines are prepared. The active ingredient of such vaccines is a synthetic protein, which is a conjugate with an immunogenic carrier protein of a synthetic peptide with a sequence which includes a sequence which is substantially the same as a substantial portion of the sequence of the acetylcholine receptor-binding segment of the rabies virus coat protein. Anti-rabies antisera, and anti-rabies antibodies, are prepared by injecting a mammal with a synthetic protein of the invention in a manner that induces an immune response in the mammal against the synthetic protein. Hybridomas which secrete anti-rabies antibodies, which bind to specific epitopes on or near the acetylcholine receptor binding segment on the rabies virus coat glycoprotein, are prepared with B cells immunized in vitro with a synthetic peptide or synthetic protein of the invention or taken from a mammal inoculated with such a peptide or protein. The anti-rabies vaccines of the invention avoid risks associated with currently available anti-rabies vaccines. The antisera and antibodies of the invention are useful therapeutically to induce passive anti-rabies immunity in a mammal that has been exposed to rabies virus. The antisera and antibodies are also useful for diagnosing whether a mammal is rabid and whether a mammal has been exposed to live rabies virus.
Celecoxib

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.

Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dosedependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors or the ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

No information is available from controlled clinical studies regarding the use of SEGLENTIS in patients with advanced renal disease. The renal effects of celecoxib may hasten the progression of renal dysfunction in patients with preexisting renal disease.

Correct volume status in dehydrated or hypovolemic patients prior to initiating SEGLENTIS. Regularly evaluate renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of SEGLENTIS [see Drug Interactions (7)]. Use of SEGLENTIS in patients with advanced renal disease is not recommended [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Hyperkalemia

Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with NC. To directly test this possibility, we used sensitive and quantitative single-cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34-fold fewer infected cells per million PBMC. These results reveal that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. Our findings show that proviral silencing is not a key mechanism for viremic control and will help to refine strategies toward achieving HIV remission without ART.
Novel rehabilitation methods, that specifically target decreased muscle activation due to joint pathology prior to strength training, have elicited greater improvements in muscle function and self-reported disability compared to traditional therapies. Preliminary evidence suggests ankle joint mobilization can improve contributions of spinal influences on ankle muscle activation in individuals with ankle joint pathology, but there is a considerable gap in understanding cortical contributions to muscle activation following joint injury. It is unknown how joint mobilization concurrently affects cortical and spinal neural motor pathways, as well as clinical measures of patient function. The overall aim of this grant is to determine the immediate effects of talocrural joint mobilization on cortical and spinal muscle activation of the fibularis longus (peroneus) and soleus muscles in individuals with chronic ankle instability (CAI). The secondary aims of this study will examine changes in ankle dorsiflexion range of motion (ROM) and dynamic balance. This innovate approach will provide the necessary scientific knowledge regarding the potential mechanism and efficacy of joint mobilization.
Medox. 2 capsules x 2 daily, 320 mg daily.
Patients receive enzalutamide 160 mg PO QD, abiraterone 1000 mg PO QD, and prednisone 5 mg PO BID. Treatment will continue until confirmed disease progression or unacceptable toxicity.
PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) have been shown to benefit from triple therapy commonly delivered by multiple-inhaler triple therapy (MITT); however, the complexity of MITT regimens may decrease patient adherence. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a once-daily single-inhaler triple therapy (SITT), became available in the United States (US) in 2017, but real-world data comparing outcomes for SITT versus MITT are currently limited. This study compared outcomes among patients with COPD initiating MITT versus SITT with FF/UMEC/VI who were either Medicare Advantage with Part D (MAPD) beneficiaries or commercial enrollees in the US.
METHODS: Retrospective study using administrative claims data from the Optum Research Database for patients with COPD who initiated FF/UMEC/VI or MITT between September 1, 2017, and March 31, 2019 (index date: first pharmacy claim for FF/UMEC/VI cohort; earliest day of ≥30 consecutive days-long period of overlap in the day's supply of all triple therapy components for MITT cohort). COPD exacerbations, adherence to triple therapy, and all-cause and COPD-related health care resource utilization (HCRU) and costs were compared between FF/UMEC/VI and MITT initiators.
RESULTS: In total, 4659 FF/UMEC/VI initiators and 9845 MITT initiators for the MAPD population, and 821 FF/UMEC/VI initiators and 1893 MITT initiators for the commercial population were included in the study. MAPD beneficiaries initiating FF/UMEC/VI had a significantly lower annual rate of severe exacerbations compared to MITT initiators (0.26 vs 0.29; p=0.014). They also had a significantly higher mean adherence (proportion of days covered) (0.51 vs 0.37; p<0.001) and significantly lower all-cause and COPD-related inpatient stays compared to MITT initiators ([32.02% vs 34.27%; p=0.017], [16.09% vs 17.72%; p=0.037]). Trends were similar among the commercial population, but the results were not statistically significant.
CONCLUSION: FF/UMEC/VI initiators had significantly fewer severe exacerbations, higher triple therapy adherence, and lower HCRU costs compared to MITT initiators for MAPD beneficiaries.
BACKGROUND: Pulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored.
METHODS: To determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases.
RESULTS: c-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease.
CONCLUSIONS: These results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis.
A pharmaceutical composition of high drug loading comprising an active pharmaceutical ingredient (API) and pharmaceutical acceptable additives, which include glass-solution forming additive and/or eutectic-mixture forming additive, is provided. The composition is dispersed uniformly to form a hybrid solid dispersion consisting of crystalline-suspension, glass-solution and/or eutectic-mixture, where the crystalline API is uniformly distributed in the hybrid solid dispersion and exists in nano/micro particle size range. The amorphous API, when present, is uniformly distributed in the hybrid solid dispersion. The API may exist in different chemical and/or physical forms. The API is present in an amount of from more than about 50% wt/wt to about 90% wt/wt with respect to the total amount of the active pharmaceutical ingredient and the pharmaceutically acceptable glass-solution forming and/or eutectic-mixture forming additives. At least about 50% wt/wt of the API is dispersed in the crystalline-suspension and at least about 5% wt/wt of the API is dispersed in the glass-solution and/or eutectic-mixture. The pharmaceutical composition offers excellent dissolution rate, superior chemical and physical stability, and minimum drug-drug/drug-excipient incompatibility. The composition is beneficial for reducing the overall tablet/capsule size for low water-soluble drugs requiring high drug loading or dosage, including combination drugs.
Overdose of protamine sulfate may cause bleeding. Protamine has a weak anticoagulant effect due to an interaction with platelets and with many proteins including fibrinogen. This effect should be distinguished from the rebound anticoagulation that may occur 30 minutes to 18 hours following the reversal of heparin with protamine.

Rapid administration of protamine is more likely to result in bradycardia, dyspnea, a sensation of warmth, flushing, and severe hypotension. Hypertension has also occurred.

The median lethal dose of protamine sulfate is 50 mg/kg in mice. Serum concentrations of protamine sulfate are not clinically useful. Information is not available on the amount of drug in a single dose that is associated with overdosage or is likely to be life-threatening.