anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PROBLEM TO BE SOLVED: To provide formulations used for treating celiac sprue and/or dermatitis herpetiformis.SOLUTION: The pharmaceutical formulations of glutenase enzymes are provided. The enzymes include prolyl endopeptidases (PEP), e.g. the Myxococcus xanthus PEP; and endoprotease, e.g. Hordeum vulgare subsp. vulgare EPB2, biologically active fragments or derivatives thereof. Certain gluten oligopeptides known to be resistant to cleavage by gastric and pancreatic enzymes are digested by such enzymes, thereby preventing or relieving their toxic effects in celiac sprue or dermatitis herpetiformis patients. The formulations are useful especially for the treatment of celiac sprue or dermatitis herpetiformis patients.
BACKGROUND: Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.
METHODS: Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.
RESULTS: In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.
CONCLUSIONS: In a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.
Previous studies indicate that obesity is a risk factor of suicide behaviors among adolescents. Whether this association has remained consistent during the ongoing obesity epidemic remains unknown. The time trends of the obesity-suicide association were examined using the 1999-2019 biannual Youth Risk Behavior Survey data (n = 161,606). Prevalence odds ratio of suicide behaviors among adolescents with obesity (vs. adolescents with no obesity) for each survey year and time trends using National Cancer Institute Joinpoint regression analysis was calculated. For each year post-baseline, there was a significant increase of prevalence odds ratio of 1.4 (1.2-1.6)-1.6 (1.3-2.0) for suicide ideation, 1.3 (1.1-1.7) -1.7 (1.4-2.0) for plan, and 1.3 (1.0-1.7) -1.9 (1.5-2.4) for an attempt, except for the 2013 survey for attempt (1.19 [0.9-1.6]). Significant positive trends were found from1999 to 2019 for ideation and plan, with biannual %-changes of + 0.92 and + 1.22%, respectively. Adolescents with obesity have consistently higher odds of engaging in suicide behaviors than their peers without obesity since the beginning of the United States obesity epidemic, and this association grew stronger as the obesity epidemic continued.
Following enrollment, leukapheresis product will be obtained in the blood donor facility at MSKCC and cryopreserved in the Cell Therapy and Cell Engineering Facility (CTCEF). Before protocol treatment, the leukapheresis product will be thawed, and T cell isolation, transduction, and expansion of iCasp928z T cells will be performed in the MSKCC CTCEF Facility. It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment.
The migratory and invasive capabilities of melanoma cells contribute to metastasis. Therefore, targeting the genes driving these processes can support melanoma therapy. Rab27A and Rab27B contribute to tumor formation progression in many types of cancer through various mechanisms, including the secretion of small extracellular vesicles (sEVs). We explored the role of these GTPases in melanoma cell functioning in three RAB27A knockout (KO) cell lines (A375, DMBC12, and SkMel28) and a double RAB27A/B KO A375 cell line. The loss of RAB27A impaired the migration and invasion of DMBC12 and SkMel28 cells; however, the behavior of highly aggressive A375 cells was unaffected. The RAB27A/B double knockout moderately decreased the migratory capacity of A375 cells without disturbing their invasiveness. Additionally, the silencing of RAB27A did not affect the number and mean size of the sEVs, despite some alterations in the protein content of the vesicles. Both Rab27 isoforms can, at least partially, act independently. The potential role of Rab27A in the functioning of melanoma cells depends on the individual character of the cell line, but not on its basal expression, and seems to be unrelated to the secretion of sEVs.
Muscle mass and strength are critical determinants not only of a person's quality of life and functional independence, but also metabolic health, as muscle is the organ primarily responsible for insulin-mediated glucose uptake. The elderly suffer obligatory losses of muscle mass and strength, exacerbated by illness and physical inactivity. Progressive resistance exercise training (PRT) is the most effective intervention identified to improve muscular strength, and combat the muscle atrophy of aging (sarcopenia); however, overall the muscle response to PRT is blunted in the elderly and variability of response increased, with some individuals actually losing muscle mass. The Bamman and Peterson labs have independently been studying the molecular and cellular mechanisms underlying the "non-responder" phenotype, with the goal of identifying novel intervention strategies to promote mass and strength gains to improve function. We hypothesize that the abundance of anti-inflammatory, alternatively activated M2 macrophages in muscle predicts response to PRT in the elderly; those with the highest number of M2 macrophages and lowest inflammatory gene expression prior to the start of training gained the most mass. Further, we determined that metformin treatment increased M2 macrophage abundance, and decreased inflammatory cytokine gene expression. These provocative findings have led us to our central hypothesis that adjuvant metformin may improve the responses to PRT in the elderly by altering the muscle tissue inflammatory environment, thereby enhancing mechanisms that drive PRT-induced myofiber hypertrophy.
BACKGROUND: TCF4 acts as a transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5 motif. Dominant variants in TCF4 are associated with the manifestation of Pitt-Hopkins syndrome, a rare disease characterized by severe mental retardation, certain features of facial dysmorphism and, in many cases, with abnormalities in respiratory rhythm (episodes of paroxysmal tachypnea and hyperventilation, followed by apnea and cyanosis). Frequently, patients also develop epilepsy, microcephaly, and postnatal short stature. Although TCF4 is expressed in skeletal muscle and TCF4 seems to play a role in myogenesis as demonstrated in mice, potential myopathological findings taking place upon the presence of dominant TCF4 variants are thus far not described in human skeletal muscle.
METHOD: To address the pathological effect of a novel deletion affecting exons 15 and 16 of TCF4 on skeletal muscle, histological and immunofluorescence studies were carried out on a quadriceps biopsy in addition to targeted transcript studies and global proteomic profiling.
RESULTS: We report on muscle biopsy findings from a Pitt-Hopkins patient with a novel heterozygous deletion spanning exon 15 and 16 presenting with neuromuscular symptoms. Microscopic characterization of the muscle biopsy revealed moderate fiber type I predominance, imbalance in the proportion of fibroblasts co-expressing Vimentin and CD90, and indicate activation of the complement cascade in TCF4-mutant muscle. Protein dysregulations were unraveled by proteomic profiling. Transcript studies confirmed a mitochondrial vulnerability in muscle and confirmed reduced TCF4 expression.
CONCLUSION: Our combined findings, for the first time, unveil myopathological changes as phenotypical association of Pitt-Hopkins syndrome and thus expand the current clinical knowledge of the disease as well as support data obtained on skeletal muscle of a mouse model.
The invention discloses a multi-mode portal high-pressure noninvasive evaluation system based on deep learning, which is characterized by comprising the following steps: a 2D backbone network branch and a 3D backbone network branch; two multiscale sensing modules; and (5) classifying the heads. The invention uses a deep learning model, combines CT and endoscopic image multi-mode data, noninvasively evaluates portal pressure, improves prediction accuracy, realizes more effective clinical decision and meets the multi-level medical condition management requirement. Compared with the prior art, the invention has the following advantages: through deep learning, end-to-end portal pressure noninvasive assessment is completed. The characteristics of manual design and excessive manually set super parameters in the traditional image group learning process are avoided, the flow is shortened, and the diagnosis efficiency is improved; combining both CT and endoscopic images. Endoscopic examination can visually present the degree of esophageal and gastric varices, and is closely related to portal vein pressure and prognosis. And combining CT and endoscopic images to improve the accuracy of the model.
Exercise is essential for building and maintaining bone mass and strength, but recent work has raised the possibility that current exercise recommendations for bone health may not be appropriate. There is strong evidence that a single bout of vigorous exercise has an acute catabolic effect in bone (i.e., increased resorption) that lasts several hours. This is mediated by a decrease in serum calcium (Ca) during exercise, which stimulates parathyroid hormone (PTH) secretion. PTH then activates bone resorption to mobilize Ca from bone, presumably to prevent the decrease in serum Ca from progressing to a harmful level. This cascade of events can be markedly attenuated by minimizing the decline in serum Ca during exercise via either intravenous or oral Ca administration. The timing of Ca supplementation relative to exercise is likely important, because it must be available for gut absorption during exercise. Interestingly, repeated pharmacologic stimulation of the PTH receptor with PTH analogs (teriparatide, abaloparatide) has anabolic effects on bone, suggesting that repeated exercise-induced increases in PTH could have a chronic anabolic skeletal effect, in addition to the acute catabolic effect, which may be apparent only after repeated exercise sessions. If this is the case, suppressing the PTH response with pre-exercise Ca supplementation may not be appropriate. In this context, this proof-of-concept study will include a short exercise intervention consisting of treadmill exercise at 70% to 80% of maximal heart rate, 60 minutes per day, 4 days per week, for 4 weeks. Serum markers of bone formation and resorption will be measured before, during, and for 24 hours after the 1st, 8th, and 16th exercise sessions to address two questions: 1) Does the acute catabolic response of bone to a single bout of exercise continue to occur with repeated exercise sessions (i.e., exercise training)? 2) Does exercise training also generate an anabolic PTH-mediated bone response, similar to the anabolic response to PTH analog therapy? If the answers to questions 1 and 2 are YES (persistent catabolic signal) and NO (lack of anabolic signal), this will support the need for the randomized controlled trial (RCT), which will evaluate whether taking Ca before exercise to attenuate the acute catabolic response improves skeletal adaptations to exercise training. The overarching goal is to improve the currently imprecise recommendations for exercise to improve and maintain bone health. This research is of high relevance to Veterans, who are at increased risk of hip fracture when compared with non-Veterans. Further, because osteoporosis in men is under-recognized, under-diagnosed, and under-treated, providing male Veterans with an effective non-pharmacologic therapeutic option to reduce fracture risk may help close this treatment gap. The potential impact of this research also extends beyond Veterans. It could lead to reduced risk of exercise-related bone injury (i.e., stress fractures) in active duty military personnel and athletes and to improved bone health in the general population.
Patients over the age of 18 who presented to the emergency department of a tertiary care hospital with complaints of cough, dyspnea, chest pain, tachycardia, hemoptysis, and syncope, and were diagnosed with pulmonary embolism (PE) confirmed by pulmonary computed tomographic angiography (CTPA), were included in our study. Informed consent was obtained from the patients who were stable and from the relatives of the patients who were unstable. Plethysmographic variability index (PVI) and Perfusion index (PI) levels were automatically obtained 2 minutes after the device was attached, using a probe placed on the index finger of the hand while the patient was lying supine. PI and PVI measurements and data were collected consecutively by the same individual. The measurements were taken using the Masimo Radical-7® Pulse CO-Oximeter, which is approved by the U.S. Food and Drug Administration.
Subjects will be administered the initial dose of mirtazapine, with dosage progressively increased over the course of the study. The initial dose of mirtazapine is 15 mg tablet, once per day. The dose will be increased weekly as tolerated up to 45 mg per day. The dose will be increased by 15 mg each week if the lower dose is tolerated without significant side effects. That is to say, the subject will take 15 mg/day every day for the first week, 30 mg/day every day for the second week, and 45 mg/day every day for the third week, with the option of the subject continuing the medication for the remainder of the pregnancy. If subjects choose to discontinue the mirtazapine, there will be a tapering regimen: if a patient is taking 45 mg at the end of week 3, they will begin a taper (by week) of 30 to 15 to 7.5 to 0 mg. If they relapse or has discontinuation symptoms, the previous effective dose will be given. They may attempt to taper again with the same approach.
A registered polysomnographic technologist will perform a titration starting at 4 cm water (H2O) and adjust this value as needed to identify the optimal pressure to achieve an Apnea Hypopnea Index (AHI) \<5 (including rapid eye movement sleep in the supine position). After PAP titration, subjects will be instructed to use the machine at the optimal pressure every night for 3 months. Compliance will be defined as: ≥4 hours use on 70% of nights and average use ≥6 hours per night.
<P>PROBLEM TO BE SOLVED: To provide method for rapidly and efficiently preparing protein-polymer conjugates.  <P>SOLUTION: The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the present invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB 1. The present invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.  <P>COPYRIGHT: (C)2011,JPO&INPIT
Subject receiving a stable dose of enzalutamide 160 mg once daily will receive GSK2636771 following a modified 3+3 dose escalation procedure (Cohort -1: 200 mg, Cohort 1: 300 mg and Cohort 2: 400 mg) to evaluate the safety and PK for each combination dose level and to guide selection of the RP2D of the combination. If the combination doses in Cohort 1 are not tolerable, lower doses as defined in the de-escalation cohort (Cohort -1) will be evaluated. If the de-escalation cohort (Cohort -1) is not tolerable, further dose-escalation using a continuous daily dosing schedule for both compounds simultaneously will be terminated. Additional dose levels of GSK2636771 or alternative dosing schedules may be explored based upon ongoing assessment of safety and PK. Dose modification decisions will be made utilizing all available data at the end of each DLT determination period (28 days).
OBJECTIVES: This study aimed to report the complication rate associated with open reduction and internal fixation (ORIF) of mandibular condyle fractures in Oman.
METHODS: This retrospective cohort study was conducted among patients who underwent ORIF of mandibular condyle fractures at Al-Nahdha Hospital and the Sultan Qaboos University Hospital in Muscat, Oman, from January 2008 to December 2020. Data collected included patient demographics, fracture aetiology, fracture side and type, surgical approach and recorded complications and outcomes.
RESULTS: A total of 68 patients (59 males and 9 females; mean age of 30.1 years) with 83 mandibular condyle fractures underwent ORIF during the study period. Subcondylar fractures were the most common type, occurring in 62.7% of patients, while bilateral fractures were observed in 21 (30.8%) patients. The most common surgical approach was retromandibular, used in 42.2% of patients. The overall complication rate was 42.6%, with the most frequently reported complications being transient facial nerve palsy (18.1%), malocclusion (14.7%) and restricted mouth opening (10.3%). Subsequent surgical interventions to correct malocclusion were performed in 6 cases. There was no statistically significant association between the overall complication rate and the patients' clinical characteristics.
CONCLUSION: Although ORIF of mandibular condyle fractures generally offers favourable outcomes, it carries a risk of complications.
Gastroesophageal reflux disease (GERD) is a chronic relapsing acid-peptic disorder that is caused by the reflux of gastric or duodenum content. Non-erosive reflux disease（NERD）, which account for 70%, is the most common type of GERD in the Asian population. Diarrhea-Predominant Irritable Bowel Syndrome（IBS-D）is the mainly subtype of IBS, and the prevalence was found to be 46% in IBS. Both diseases aforementioned are common and frequent chronic diseases in the world, and the pathogenesis of which has not been fully defined. Current studies have shown that GERD can present in patients with IBS, vice versa. Up to 79% of patients with IBS co-exist with GERD-like symptoms, and 71% of patients with GERD co-exist with IBS-like symptoms. For those patients, they suffer from more serious symptom manifestation, anxiety, and worse life quality those with solely disease. The diagnosis and treatment of Functional gastrointestinal disorders (FGIDs) mostly based on the idea of segmental diagnosis and single-target therapy in modern medicine, and there is lack of effective treatment for overlapping gastrointestinal symptoms. The advantages of holistic diagnosis therapy and individualized treatment in Traditional Chinese Medicine（TCM）have attracted international attention, but there is still lack of high-level evidence-based medical evidence for the treatment of symptom overlap in FGIDs in TCM. In this study, we propose to conduct a multicenter, randomized, double-blind, placebo-controlled clinical study of WPQW granule for the treatment of NERD overlapping IBS-D to evaluate the efficacy and safety of WPQW granule with the aim of obtaining high-level evidence-based medical evidence.
This is an open-label, Phase 2a pilot study of Immunicom's LW-02 column- combined with low-dose chemotherapy or immunotherapy in patients who have failed first-line treatment or employed as monotherapy in patients who have failed second-line therapy-to evaluate the short-term and long-term safety, tolerability and effectiveness of these approaches in removing sTNF-Rs and the potential for disease control in advanced, refractory NSCLC patients. Along with LW-02 column immunopheresis, patients enrolled in Arm 1 will receive combination immunotherapy with atezolizumab and patients enrolled in Arm 2 also will receive combination chemotherapy with paclitaxel. Patients in Arm 3 will be treated with LW-02 column immunopheresis alone as a third-line treatment regimen, assuming the first-line treatment included a platinum salt. Following study qualification, patients will be assigned to the appropriate treatment. All patients may receive up to 48 LW-02 column-based immunopheresis treatments over a 16-week (4-month) period with up to 3 treatments per week). Importantly, each LW-02 immunopheresis treatment should last up to 3 hours and process, approximately, 2 times the patient's plasma volume (2PV).

Each patient assigned to the treatment with LW-02 column-based immunopheresis will require central vascular access for the procedure. In general, a cuffed, tunneled dual-lumen catheter will be inserted into a central vein and remain in situ throughout the 16-week treatment phase (or longer if additional treatment is clinically indicated). The catheter will be used to connect the inlet and return lines of the apheresis system to the patient. Immunopheresis treatments will be performed using the LW-02 column used inline with a centrifugal apheresis system that allows for secondary plasma processing system (eg, the Terumo BCT Spectra Optia Apheresis System® or alternate apheresis system). Proper anticoagulation of the centrifugal apheresis device is generally provided by utilizing acid citrate dextrose formula A (ACD-A).

Patients will be followed and clinically evaluated for two-years posttreatment. In Year 1, patients will be clinically evaluated at 3, 6, 9, and 12 months from the end-of-treatment (EOT) visit. In Year 2 quarterly (every 3 months) telephone contacts will be made to determine overall survival.
The invention discloses application of a compound AJ-4 in the preparation of a medicine for treating or preventing influenza virus. The compound AJ-4 is a compound as shown in the formula (I). The invention firstly requests to protect the application of the compound as shown in the formula (I) in the preparation of a medicine for inhibiting influenza virus. The invention also protects a medicine for inhibiting influenza virus. An active component of the medicine is the compound as shown in the formula (I). The inhibition on influenza virus can be reflected as an inhibition on replication of influenza virus and/or an inhibition on activity of influenza virus particle ribosome. The invention has great value in controlling influenza virus.