anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Opioid drugs as a group have withstood the test of time in their ability to relieve pain. Morphine is the most frequently used "gold standard" opioid for managing surgical pain. Like other opioids, morphine has a narrow therapeutic index and a large inter-patient variability in response. Certain genetic and non-genetic factors are believed to be responsible for variations in analgesic responses and side effects with morphine. Genetic factors determining an individual's pain sensitivity and regulating morphine's pharmacokinetics (transporters) and pharmacodynamics (receptors and signal transduction elements) are likely contributors to such variability. Frequent variations in analgesic response are unfortunately clinically significant with inadequate pain relief at one end of the spectrum of responses and major side effects including potentially fatal respiratory depression due to relative overdosing at the other end. Much of the inter-individual variability in response to a dose of morphine following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a subset of the genes that encode proteins involved in pain perception, opioid transport and opioid receptor signaling. The genetic variants of mu opioid receptor (OPRM1), Catechol-O-methyltransferase (COMT), the Multi Drug Resistance Transport protein gene ABC B1, have been associated in small adult studies with varying levels of pain sensitivity, analgesic response to opioids and susceptibility to serious side-effects of opioids such as respiratory depression, sedation and vomiting. Effective and safe acute postoperative pain relief in a subset of children is clinically difficult due to frequent clinical variations in perceptions of pain and responses to opioids. To the investigator's knowledge, there is no other study attempting to individualize perioperative analgesia in children. The investigator's long term goal is to identify factors that modify pain sensitivity and responses to morphine in order to develop more effective, safe and tailored therapies. The overall objective of this application is to evaluate the contribution of individual and combined affects of genetic polymorphisms in OPRM1, COMT and ABC B1 genes and their association with postoperative pain relief and adverse effects with morphine. The investigator's central hypothesis is that specific genetic polymorphisms in genes involved in pain perception, opioid transport and opioid receptor signaling pathways contribute significantly to pain sensitivity, morphine consumption, and morphine's side-effects in children.

This study will also explore a set of other important SNPs that might influence pain perception and responses to morphine in children. The data will be analyzed looking at pain scores, morphine doses, incidence of side-effects of morphine including respiratory depression, sedation, vomiting and itching.
Participants will be scanned in an fMRI session lasting approximately 45-50 minutes and will be shown negative images for which they will have to take on a cognitive reappraisal tactic. All participants will be taken through the scanner with the same reappraisal protocol for each participant.
Transobturator sling (TOT) is placed according to the original description. Instead of a "Metzenbaum Scissor" which should guarantee the distance between the urethra and the sling a Hegar dilator sound of 4 mm diameter is used (Hegar 4). An additional Hegar dilator sound of 8 mm is placed in the urethra before tightening the sling and suturing the vaginal skin.
Patients with acute exacerbation of severe COPD, requiring invasive mechanical ventilation will be treated with vv-ECCO2R (Extracorporeal carbon dioxide removal) to facilitate early extubation. ECCO2R is used in a standard configuration with either double lumen cannula (22-24Fr) or two small single vessel cannulas (15-19 Fr), allowing a blood flow rate between 1-1.75 L/min.
The present invention relates to a composition for preventing, improving, or treating hair loss and a composition for promoting hair growth or hair regrowth, containing a Connarus semidecandrus Jack. extract. According to the present invention, it has been identified that when a testosterone-induced alopecia animal model is treated with the Connarus semidecandrus Jack. extract, hair growth is promoted, hair length and thickness are also increased, the expression of androgenic receptors and apoptosis-related factors is inhibited, the survival and proliferation of human dermal papilla cells are promoted, and the activity of 5-α reductase is inhibited. Therefore, the Connarus semidecandrus Jack. extract of the present invention can be effectively and variously used for preventing or treating hair loss and promoting hair growth or hair regrowth.
BACKGROUND AND AIM: Patients with liver cirrhosis often face a grave threat from infected ascites (IA). However, a well-established prognostic model for this complication has not been established in routine clinical practice. Therefore, we aimed to assess mortality risk in patients with liver cirrhosis and IA.
METHODS: We conducted a retrospective study across three tertiary hospitals, enrolling 534 adult patients with cirrhotic liver and IA, comprising 465 with spontaneous bacterial peritonitis (SBP), 34 with bacterascites (BA), and 35 with secondary peritonitis (SP). To determine the attributable mortality risk linked to IA, these patients were matched with 122 patients with hydropic decompensated liver cirrhosis but without IA. Clinical, laboratory, and microbiological parameters were assessed for their relation to mortality using univariable analyses and a multivariable random forest model (RFM). Least absolute shrinkage and selection operator (Lasso) regression model was used to establish an easy-to-use mortality prediction score.
RESULTS: The in-hospital mortality risk was highest for SP (39.0%), followed by SBP (26.0%) and BA (25.0%). Besides illness severity markers, microbiological parameters, such as Candida spp., were identified as the most significant indicators for mortality. The Lasso model determined 15 parameters with corresponding scores, yielding good discriminatory power (area under the receiver operating characteristics curve = 0.89). Counting from 0 to 83, scores of 20, 40, 60, and 80 corresponded to in-hospital mortalities of 3.3%, 30.8%, 85.2%, and 98.7%, respectively.
CONCLUSION: We developed a promising mortality prediction score for IA, highlighting the importance of microbiological parameters in conjunction with illness severity for assessing patient outcomes.
Techniques for patient data management include obtaining medical history data for a patient from a database, the medical history data including a history of one or more diagnostic events, one or more treatment events, and clinical outcome events for each of the patients. For each patient, based on the medical history data, a computing system generates a patient path including a graph including nodes of one or more diagnostic events, the one or more treatment events, and the clinical outcome event. The computing system receives, via an interface, one or more criteria to select a subset of the patient paths of the patient. The computing system selects a graph representing the subset of the patient paths based on the one or more criteria. The computing system aggregates the subset of the patient paths into a consolidated graph. The computing system displays the merged graph in the interface.
This is an open-label (all participants of this study know the identity of the intervention) and multicenter (study conducted at multiple sites) study. This study will be conducted in 2 parts. Both the parts of the study will consist of screening phase (4 weeks), treatment period (24 weeks), and a post-treatment follow-up (24 weeks). A total of 30 participants will be enrolled in Part 1 and Part 2 of the study. A minimum of 9 participants were planned to receive cyclosporine as stable immunosuppressant therapy and a minimum of 9 participants were planned to receive tacrolimus as stable immunosuppressant therapy during Part 1. All participants will be receiving tacrolimus as stable immunosuppressant therapy during Part 2. In Part 1 of the study, participants with Metavir score of F1-F2, will receive a combination of study drugs - simeprevir, daclatasvir, and ribavirin for 24 weeks. In Part 2 of the study, participants with Metavir score F1-F4 will receive a dosing regimen of study drugs based on the data from Part 1 of the study. Safety evaluations will include assessments of adverse events, clinical laboratory tests, urinalysis, electrocardiogram, vital signs, and physical examination. The total study duration for each participant will be approximately 52 weeks.
PCT No. PCT/US88/02991 Sec. 371 Date Jun. 30, 1989 Sec. 102(e) Date Jun. 30, 1989 PCT Filed Aug. 30, 1988 PCT Pub. No. WO89/01779 PCT Pub. Date Mar. 9, 1989Molecular decoyants are chemical structures which functionally resemble an endogenous receptor. They may be used for the treatment of humans or other animals which have been subjected to a foreign agent which exerts an undesired effect only after first binding to that endogenous receptor. A decoyant is a fraction of an endogenous receptor which retains the essential elements of the binding site of the receptor for the foreign agent or is a synthetic or biosynthetic derivative thereof. The  alpha 184-200 amino acid sequence of Torpedo californica acetylcholine receptor is an example of a decoyant which protects against curarimimetic neurotoxins. Another example is the fraction of the CD4 receptor which retains the essential elements of the receptor for protection against HIV.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but dangerous side effect of adenoviral-vectored COVID-19 vaccines. VITT had been linked to production of autoantibodies recognizing platelet factor 4 (PF4). Here, we characterize anti-PF4 antibodies obtained from a VITT patient's blood. Intact mass measurements indicate that a significant fraction of these antibodies represent a limited number of clones. MS analysis of large antibody fragments (the light chain and the Fc/2 and Fd fragments of the heavy chain) confirms the monoclonal nature of this component of the anti-PF4 antibodies repertoire and reveals the presence of a mature complex biantennary N-glycan within the Fd segment. Peptide mapping using two complementary proteases and LC-MS/MS was used to determine the amino acid sequence of the entire light chain and over 98% of the heavy chain (excluding a short N-terminal segment). The sequence analysis allows the monoclonal antibody to be assigned to the IgG2 subclass and verifies that the light chain belongs to the λ-type. Incorporation of enzymatic de-N-glycosylation into the peptide mapping routine allows the N-glycan in the Fab region of the antibody to be localized to the framework 3 region of the VH domain. This novel N-glycosylation site is the result of a single mutation within the germline sequence. Peptide mapping also provides information on lower-abundance (polyclonal) components of the anti-PF4 antibody ensemble, revealing the presence of all four subclasses (IgG1-IgG4) and both types of the light chain (λ and κ). This case study demonstrates the power of combining the intact, middle-down, and bottom-up MS approaches for meaningful characterization of ultralow quantities of pathogenic antibodies extracted directly from patients' blood.
Approximately 43% of children under-5 are at risk of not attaining their developmental potential. Parenting interventions are recommended for improving early childhood development during the earliest years of life. However, there is limited evidence regarding the delivery and effectiveness of parenting interventions to promote early child development outcomes in Kenya specifically. This cluster-randomized trial aims to evaluate the effectiveness of the Moments That Matter® (MTM) Program on early child development and caregiving outcomes in two selected counties in western Kenya. The MTM Program will be implemented by the Anglican Church of Kenya Development Services - Nyanza (ADS-Nyanza), a faith-based organization focused on supporting integrated community-based programs to support the health, wellbeing, and development of the most vulnerable children and families. Various stakeholders - including community volunteers, faith leaders, and ECD committees - will be mobilized and trained to deliver nurturing care and ECD services over an 18-month program period. This trial will enroll primary caregivers of children 0-18 months of age and longitudinally follow the study cohort to ultimately compare changes in early child development and caregiving outcomes between the intervention and waitlist-control study arms. In addition to the impact evaluation, a qualitative implementation evaluation will be conducted to assess quality of delivery, identify factors that influence program effectiveness, and determine program potential for sustainability and scale-up.
The present invention relates to derivatives of a GLP-1 analog of the general formula I, which derivatives comprise a side chain attached to a Lys residue at position 34, 35, 36, 37, 38 or 39 of the GLP-1 analog. The side chain comprises a branched linker, first and second extensions, and a forward linker. The branched linker is linked to a Lys residue of the GLP-1 analogue via the front linker and to the first and second extensions via the first and second rear linkers, respectively. The branched linker may for example be a trivalent radical of Lys. The first and second extensions are C20 diacid. Various connector elements can be used in the front connector as well as in the two rear connectors. The invention also relates to novel GLP-1 analogs, novel side chain intermediates and their preparation and use for the preparation of biologically active peptides and proteins, as well as pharmaceutical compositions and medical applications of the analogs and derivatives. The derivatives have an extremely long half-life while maintaining satisfactory efficacy, which makes them potentially suitable for once-a-month administration.
Dry powder vancomycin compositions and methods for administering and preparing such compositions. The compositions of the disclosure comprise vancomycin or a pharmaceutically acceptable salt thereof, and a hydrophobic amino acid, wherein the hydrophobic amino acid is present in an amount less than 50% by weight of the composition, and wherein the composition is a substantially amorphous dry powder. A composition of the present disclosure may be administered to a subject via pulmonary administration in an amount effective to treat and/or prevent a bacterial infection in the subject. Administration of an effective amount of a composition of the present disclosure may be particularly useful in treating a gram-positive bacterial infection in a subject suffering from pneumonia, cystic fibrosis, bronchiectasis, or other chronic lung disease with a bacterial infection of the subject’s airway and/or lung. The compositions may further comprise a hydrophobic amino acid which may be selected from the group consisting of: tryptophan, tyrosine, leucine, trileucine, and phenylalanine. The compositions may further comprise a carbohydrate bulking agent carbohydrate bulking agent which may be selected from the group consisting of: lactose, mannitol, trehalose, raffinose, and a maltodextrin.
The present invention is directed to Tofacitinib mono-oxalate salt. The Tofacitinib mono-oxalate salt can be in amorphous form. The invention is also directed towards apharmaceutical composition comprising Tofacitinib mono-oxalate salt, and a process for preparing the composition. The Tofacitinib mono-oxalate salt can be used to prepare Tofacitinib mono-citrate salt. Another aspect of the invention is a process for preparing Tofacitinib mono-citrate. The Tofacitinib mono-oxalate salt is also useful as a medicament for the treatment of cancer.
1. A fraction of lysine-rich histone thymus factor (TF) of mammals, capable of precipitating when contacted with serum of a human, uninfected with HIV, forming one continuous precipitation spur on the gel after two-dimensional electrophoresis in relation to the location of β -, α1- and α2- macroglobulins, and not capable of precipitating when contacted with serum of a human, infected with HIV, forming one continuous precipitation arch on the gel after two-dimensional electrophoresis in relation to the location of β -, α1- and α2- macroglobulins. 2. A TF fraction of claim 1, wherein, when methylated or unmethylated, has a pH of between 7.64 and 8.6, a molecular weight of methylated TF is about 28 kilodalton as determined by 11% non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a molecular weight of unmethylated TF is about 35 kilodalton as determined by 11% non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and has an isoelectric point of about 5.6. 3. A method of obtaining TF fraction of claim 1, comprising extracting a lysine-rich histone fraction from mammalian thymus cell nuclei by means of pepsin, contacting the lysine-rich histone fraction with a cation exchange chromatographic material, eluting the TF protein with an effective aqueous salt solution and collecting the obtained fraction. 4. A method of claim 3, wherein the cation exchange chromatography is performed on a carboxymethyl column and the TF protein is eluted by applying a linear gradient of sodium chloride at pH 6.8. 5. A method for detecting acquired immunodeficiency syndrome in a human, comprising collecting a biological sample from the subject, suspected for HIV, providing contacting of said sample with the fraction of claim 1, correlating precipitation patterns TF and aTF in a tested sample with the precipitation pattern TF and aTF obtained from a HIV infected human, by detecting localization products of precipitation respective to the zone of the location of β -, α1- and α2- macroglobulins. wherein the absence of the spur precipitaion or the presence of the broken precipitation spur within or beyond the location of β -, α1- and α2- macroglobulins proves the presence of HIV infection in a human.
Several type 2 diabetes risk prediction models have been developed but how it will perform in a Swedish population is not known. No diabetes risk prediction model is routinely used in Sweden. The aim of this study is therefore, to validate 11 non-invasive models and to evaluate the performance to predict incident type 2 diabetes in a Swedish population. A population-based cohort from the Västerbotten Intervention programme (VIP) from 1990 to 2020 will be the validation sample. Incident type 2 diabetes within 10-years of follow-up, will be determined by oral glucose tolerance test or through self-reports. A self-administered questionnaire is completed, and anthropometric, clinical, and biochemical measures are obtained at each of the health screening visits. In the statistical analysis the overall performance of the models will be compared using the Brier score. In addition. discrimination and calibration of all the models will be evaluated. Recalibration of models will be done.
PURPOSE:To obtain a stabilized oil-soluble vitamin-containing composition useful as a drug, animal drug, feed additive, nutrition auxiliary, etc., containing a carotenoid. CONSTITUTION:An oil-soluble vitamin such as vitamin K, vitamin A, coenzyme Q or vitamin D and a carotenoid (e.g. beta-carotene) are dissolved in an oil component such as colza oil or an organic solvent such as n-hexane and uniformly blended. Further the solution is optionally mixed with well-known additives (e.g. extender, coloring matter, sweetener and spice) in terms of preparation and pharmaceutically manufactured by a conventional procedure to give the aimed substance. The amount of the carotenoid added is <=0.01wt.% based on the oil-soluble vitamin to the limit of solubility of the prepared composition of carotenoid. The aimed substance can be pharmaceutically manufactured into injection, syrup, tablet, granule, ointment, cream, capsule, etc.
RNA-modifying proteins, classified as "writers," "erasers," and "readers," dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing RNA stability, functionality, and interactions. To date, over 170 distinct RNA chemical modifications and more than 100 RNA-modifying enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has been made in understanding RNA modification, the regulatory mechanisms that govern RNA-modifying proteins themselves remain insufficiently explored. Post-translational modifications (PTMs) such as phosphorylation, ubiquitination, and acetylation are crucial in modulating the function and behavior of these proteins. However, the full extent of PTM influence on RNA-modifying proteins and their role in disease development remains to be fully elucidated. This review addresses these gaps by offering a comprehensive analysis of the roles PTMs play in regulating RNA-modifying proteins. Mechanistic insights are provided into how these modifications alter biological processes, contribute to cellular function, and drive disease progression. In addition, the current research landscape is examined, highlighting the therapeutic potential of targeting PTMs on RNA-modifying proteins for precision medicine. By advancing understanding of these regulatory networks, this review seeks to facilitate the development of more effective therapeutic strategies and inspire future research in the critical area of PTMs in RNA-modifying proteins.
BACKGROUND: Respiratory diseases, including the multifactorial "swine respiratory disease complex," have a significant impact on swine production. Recently, a condition manifesting primarily in the trachea, known as hemorrhagic tracheitis syndrome (HTS), has been described in pigs. HTS is characterized by severe coughing and high mortality in finishing pigs.
CASE DESCRIPTION: This report presents the first case of HTS in an adult male pig from a Portuguese farm. The animal died without any previous clinical signs. Necropsy revealed significant thickening of the trachea. Fibrinous necrotic hemorrhagic tracheitis was identified through histopathological analysis, but no bacterial infectious agents were detected during microbiological examination.
CONCLUSION: This case underscores the need for comprehensive research, including systematic necropsies and histopathological assessments, to understand the actual prevalence of the disease, elucidate the etiology, and develop effective interventions for HTS in swine productions.
Metastatic melanoma is still a difficult-to-treat cancer type owing to its frequent resistance mechanisms to targeted and immunotherapy. Therefore, we aimed to unravel novel therapeutic strategies for melanoma patients. Preclinical and clinical studies show that melanoma patients may benefit from a treatment with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). In this study, we focus on PARP1 as a potential biomarker to predict the response of melanoma cells to PARPi therapy. We found that melanoma cells with high basal PARP1 expression exhibit significantly increased cell death after PARPi treatment owing to higher PARP1 trapping compared with melanoma cells with low PARP1 expression. In addition, we could demonstrate that PARP1 expression levels are low in nonmalignant skin cells, and metastatic melanomas show considerably higher PARP1 levels compared with primary melanomas. Most strikingly, we found that high PARP1 levels correlate with worse overall survival of late stage metastasized melanoma patients. In conclusion, we show that PARP1 might act as a biomarker to predict the response to PARPi therapy, and that in particular the late stage metastasized melanoma patients are especially sensitive to PARPi therapy owing to elevated PARP1 expression. Our data suggest that the PARPi cytotoxicity primarily will affect the high PARP1 expressing melanoma cells, rather than the low PARP1 expressing nonmalignant skin cells resulting in only low side effects.