anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.
Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.
BACKGROUND: Pulmonary hypertension, characterized by vascular remodeling, currently lacks curative therapeutic options. The dysfunction of pulmonary artery endothelial cells plays a pivotal role in the initiation and progression of pulmonary hypertension (PH). ErbB3 (human epidermal growth factor receptor 3), also recognized as HER3, is a member of the ErbB family of receptor tyrosine kinases.
METHODS: Microarray, immunofluorescence, and Western blotting analyses were conducted to investigate the pathological role of ErbB3. Blood samples were collected for biomarker examination from healthy donors or patients with hypoxic PH. The pathological functions of ErbB3 were further validated in rodents subjected to chronic hypoxia- and Sugen-induced PH, with or without adeno-associated virus-mediated ErbB3 overexpression, systemic deletion, or endothelial cell-specific ErbB3 knockdown. Primary human pulmonary artery endothelial cells and pulmonary artery smooth muscle cells were used to elucidate the underlying mechanisms.
RESULTS: ErbB3 exhibited significant upregulation in the serum, lungs, distal pulmonary arteries, and pulmonary artery endothelial cells isolated from patients with PH compared with those from healthy donors. ErbB3 overexpression stimulated hypoxia-induced endothelial cell proliferation, exacerbated pulmonary artery remodeling, elevated systolic pressure in the right ventricle, and promoted right ventricular hypertrophy in murine models of PH. Conversely, systemic deletion or endothelial cell-specific knockout of ErbB3 yielded opposite effects. Coimmunoprecipitation and proteomic analysis identified YB-1 (Y-box binding protein 1) as a downstream target of ErbB3. ErbB3 induced nuclear translocation of YB-1 and subsequently promoted hypoxia-inducible factor 1/2α transcription. A positive loop involving ErbB3-periostin-hypoxia-inducible factor 1/2α was identified to mediate the progressive development of this disease. MM-121, a human anti-ErbB3 monoclonal antibody, exhibited both preventive and therapeutic effects against hypoxia-induced PH.
CONCLUSIONS: Our study reveals, for the first time, that ErbB3 serves as a novel biomarker and a promising target for the treatment of PH.
Participants in this arm will receive brief advice about alcohol use. Sessions will occur at the baseline interview and every three months for 18 months.
1. A stable lyophilized formulation comprising recombinant human activated protein C; a bulking agent selected from the group consisting of mannitol, trehalose, raffinose, and sucrose, and mixtures thereof; and a buffer system such that on reconstitution the resulting formulation has a pH between 5.5 and 6.3. 2. The formulation of Claim 1, wherein comprising dis-(1-9)-inactivated protein C and dis-(1-10)-inactivated protein C in an amount less than 10% of total formulation weight. 3. The formulation of Claim 1, wherein comprising dis-(1-9)-inactivated protein C and dis-(1-10)-inactivated protein C in an amount less than 5% of total formulation weight. 4. The formulation of Claim 1,2 or 3, wherein the pH of the solution is between 5.9 to 6.1. 5. The formulation of Claim 4, wherein the buffer system is sodium citrate. 6. The formulation of any one of Claims 1-5, wherein further comprises a pharmaceutically acceptable salt. 7. A lyophilized formulation comprising recombinant human activated protein C, salt and excipient selected from the group consisting of mannitol, trehalose, raffinose, and sucrose, wherein the weight ratio is about 1 part activated protein C, between about 7 to 8 parts salt, and between about 5 to 7 parts excipient. 8. The formulation of Claim 7, wherein the weight to weight ratio is about 1 part activated protein C, about 7.6 parts salt and about 6 parts excipient. 9. The formulation of any one of Claims 6-8, wherein the salt is NaCl, and the excipient is sucrose. 10. The formulation of any one of Claims 6-9, wherein on reconstitution the resulting formulation comprises 5 mg/mL recombinant human activated protein C, 30 mg/mL sucrose, and 38 mg/mL NaCl. 11. Use the formulation of any one of Claims 1-10, as a medicament in the treatment of disease states involving intravascular coagulation. 12. Use the formulation of any one of Claims 1-10, as a medicament in the treatment of thrombotic stroke. 13. A unit dosage form comprising a unit dosage receptacle containing the formulation of any one of Claims 1-10.
BACKGROUND: Social jetlag, the misalignment between biological and social rhythms, can lead to adverse health outcomes. This study explored the association between social jetlag and hazardous alcohol consumption, as well as the sex differences in this association.
METHODS: This study included a nationally representative sample of Korean workers consisting of 11,462 individuals (5479 women). Social jetlag was calculated as the difference in the mid-point between sleep onset and offset on free days and workdays. Hazardous alcohol consumption was determined using the Alcohol Use Disorder Identification Test-Consumption (range 0-12), with a cutoff of ≥6 for men, ≥5 for women, and ≥3 for those aged ≥65. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs).
RESULTS: Among men, 599 out of 5983 individuals (10.0 %) had ≥120 min of social jetlag. Among women, 550 out of 5479 individuals (10.0 %) had ≥120 min of social jetlag. The prevalence of hazardous alcohol use was 56.2 % for men and 27.3 % for women. In the regression analysis, there was a significant sex interaction, where social jetlag ≥120 min was associated with hazardous alcohol consumption in female workers (OR: 1.52, 95 % CI: 1.18-1.96), but not in male workers (OR: 1.04, 95 % CI: 0.84-1.29).
CONCLUSION: High social jetlag was associated with an increased likelihood of hazardous alcohol consumption among women. Our findings underscore the importance of considering sex differences in future research and policy interventions regarding social jetlag and its associated behavior outcomes.
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD). Mortality data specific to patients with ADPKD is currently lacking; thus, the aim of this study was to estimate mortality in patients with ADPKD.
METHODS: We analyzed data from the United States Renal Data System (USRDS) for patients with ADPKD available during the study period of 01/01/2014-12/31/2016, which included a cohort of patients with non-ESRD chronic kidney disease (CKD) and a cohort of patients with ESRD. Mortality rates with 95% confidence intervals (CIs) were calculated overall and by age group, sex, and race for the full dataset and for a subset of patients aged ≥ 65 years. Adjusted mortality hazard ratios (HRs) were calculated using Cox regression modeling by age group, sex, race, and CKD stage (i.e., non-ESRD CKD stages 1-5) or ESRD treatment (i.e., dialysis and transplant).
RESULTS: A total of 1,936 patients with ADPKD and non-ESRD CKD and 37,461 patients with ADPKD and ESRD were included in the analysis. Age-adjusted mortality was 18.4 deaths per 1,000 patient-years in the non-ESRD CKD cohort and 37.4 deaths per 1,000 patient-years in the ESRD cohort. As expected, among the non-ESRD CKD cohort, patients in CKD stages 4 and 5 had a higher risk of death than patients in stage 3 (HR = 1.59 for stage 4 and HR = 2.71 for stage 5). Among the ESRD cohort, patients receiving dialysis were more likely to experience death than patients who received transplant (HR = 2.36). Age-adjusted mortality among patients aged ≥ 65 years in the non-ESRD CKD cohort was highest for Black patients (82.7 deaths per 1,000 patient-years), whereas age-adjusted mortality among patients aged ≥ 65 years in the ESRD cohort was highest for White patients (136.1 deaths per 1,000 patient-years).
CONCLUSIONS: Mortality rates specific to patients aged ≥ 65 years suggest racial differences in mortality among these patients in both non-ESRD CKD and ESRD cohorts. These data fill an important knowledge gap in mortality estimates for patients with ADPKD in the United States.
Bacterial lipopolysaccharides are able to produce neuroinflammation and dopaminergic receptors degeneration. In addition, they may produce an accumulation of α-synuclein in the area of the substantia Nigra. Recent studies have shown that α-synuclein aggregates may be present also in gastrointestinal neurons of patients with PD. This last finding led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. Forsyth et al. have discovered an impaired intestinal permeability in subjects with recently diagnosed PD, and they found positive correlations between this factor, exposure to LPS and alpha-synuclein accumulation in gastrointestinal neurons. Plasma lipoproteins play a key role in the detoxification of bacterial endotoxins. Lipoprotein chemical composition is related to their detoxing properties. To the best of investigator knowledge, the relationships between lipoprotein chemical composition and LPS in PD have not yet been investigated. Therefore, the aims of this study are: I) to evaluate the chemical composition of VLDL, LDL and HDL in subjects with PD compared to a control group; 2) to analyze the activity of plasma lipid transfer proteins and LPS plasma levels in the same groups of subjects; III) finally, to investigate the correlations between the analyzed parameters.

Subjects and method Twenty patients with PD and twenty healthy controls were recruited for the study. Fasting blood samples were taken for routine laboratory analysis and for the separation of EDTA plasma. Plasma samples stored at -80°C until were used for lipoprotein isolation and analysis and for the measurement of lipid transfer protein and LPS levels.
BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema.
METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition.
RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%).
CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.
PURPOSE:To produce the titled adsorbent by bonding a functional group having basic nitrogen atom and a polymyxin molecule to a molded article of an insoluble vinyl polymer. CONSTITUTION:The objective alexeteric adsorbent for endotoxin can be prepared by bonding a functional group having basic nitrogen atom (e.g. primary amino group, secondary amino group, tertiary amino group, quaternary ammonium group, etc.) and a polymyxin molecule (an antibiotic substance produced by Bacillus polymyxa, e.g. polymyxin A) to a molded article of an insoluble vinyl polymer (e.g. homopolymer or copolymer of styrene, vinyl chloride, acrylamide, etc., a copolymer with a polyvinyl compound such as divinylbenzene, etc.). The agent is highly effective because of its capability to decompose endotoxin and to adsorb and remove the decomposition product. Since substantial effect can be achieved even at a low immobilization density of polymyxin, the amount of polymyxin can be reduced.
A microorganism (Streptomyces sp. K03-0132, FERM ABP-10148), which belongs to Streptomyces sp. and is capable of producing active substances K03-0132A and/or K03-0132B, is cultured in a medium to thereby accumulate the active substances K03-0132A and/or K03-0132B in the culture medium. Then the active substances K03-0132A and/or K03-0132B are collected from the culture medium. Because of having an effect of elevating the activity of azole-type fungicides, the obtained active substances act on a large number of fungal infections such as deep-seated mycosis in a low dose within a short period of time and are useful in lowering the frequency of the appearance of resistant strains. It is also expected that these substances are useful in overcoming resistance.
A computer assisted method creates accurate CAD/CAM models of custom orthopedic implants is provided. Information about bone geometry is acquired through medical imaging such as CT image scans. The desired bone surface region is extracted as a polygonal mesh after processing the 3D images. A smooth and accurate B-Spline surface is fitted to the polygonal mesh that is thickened to a solid CAD model. A patient-specific customized implant is manufactured from the obtained CAD model. The patient-specific customized implant is implanted in a patient by a surgeon in an operating room. A processor based system to generate a CAD/CAM file of the patient-specific customized implant and a manufacturing system enabled to manufacture the implant from the CAD/CAM file are also disclosed.
The present invention relates to a modified antibody comprising a heavy chain and a light chain, wherein the heavy chain or/and the light chain comprises one or more first recognition site(s) for the transglutaminase from Kutzneria albida (KalbTG) or a functionally active variant thereof. The one or more first recognition site(s) are introduced at one or more selected position(s) within the antibody's heavy chain and/or light chain. The invention further relates to one or more nucleic acids encoding the modified antibody according to the invention as well as a covalent conjugate comprising (i) the modified antibody according to the invention and (ii) one or more non-antibody moieties (payload(s)) covalently conjugated to the one or more first recognition site(s) either directly or via a first linker. In certain embodiments, the non-antibody moiety comprises a therapeutic entity and optionally a second linker. The present invention further relates to a method of covalently conjugating a modified antibody according to the invention to non-antibody moieties. In case the non-antibody moiety comprises a therapeutic entity, the present invention further relates to the conjugate of the modified antibody according to the invention and the therapeutic entity as pharmaceutical composition, for use as a medicament as well as for use in treating a disease.
Patients who have received flumazenil for the reversal of benzodiazepine effects (after conscious sedation or general anesthesia) should be monitored for resedation, respiratory depression, or other residual benzodiazepine effects for an appropriate period (up to 120 minutes) based on the dose and duration of effect of the benzodiazepine employed.

This is because flumazenil has not been established in patients as an effective treatment for hypoventilation due to benzodiazepine administration. In healthy male volunteers, flumazenil is capable of reversing benzodiazepine-induced depression of the ventilatory responses to hypercapnia and hypoxia after a benzodiazepine alone. However, such depression may recur because the ventilatory effects of typical doses of flumazenil (1 mg or less) may wear off before the effects of many benzodiazepines. The effects of flumazenil on ventilatory response following sedation with a benzodiazepine in combination with an opioid are inconsistent and have not been adequately studied. The availability of flumazenil does not diminish the need for prompt detection of hypoventilation and the ability to effectively intervene by establishing an airway and assisting ventilation.

Overdose cases should always be monitored for resedation until the patients are stable and resedation is unlikely.
PROBLEM TO BE SOLVED: To obtain a glycerophosphate dehydrogenase inhibitor useful as a food additive, etc., by using a specific extract of areca nut with a hydrophilic solvent as an active component. SOLUTION: An extract obtained by extracting areca nut known as a herb drug with a hydrophilic solvent is used as an active component of the objective inhibitor. The extract is one or more substances selected from NF-86I, NF-86II, NPF-86IA, NPF-86IB, NPF86II and NPF-86IIB. The glycerophosphate dehydrogenase inhibitor is usable by adding to biscuit, tablet candy, tablet drug, bread or noodle. The inhibitor has high safety and excellent glycerophosphate dehydrogenase inhibiting activity and is easily compoundable to a food and useful for the prevention and treatment of obesity. NF-86I which is one of the active components is pale yellowish brown powder (stable in powdery form), free from distinct melting point and decomposition point and composed of 56.30% carbon, 4.61% hydrogen, <=0.2% nitrogen and <=0.3% ash and has a molecular weight of 1,000-10,000 (by dialysis tube).
Subcutaneous infiltration during surgery using 200ml of 0.2% plain ropivacaine. 50ml injected following bone preparation prior to implant cementation perpendicular to the posterior femur through the posterior joint capsule in 10ml aliquots. 30ml proximal to the suprapatellar pouch down to the femur.100ml spread into subcutaneous tissues including; collateral and cruciate ligaments, fatty and connective tissue on the anterior aspect of the incision. A 16 gauge epidural catheter inserted via a medial portal, 20ml was injected via the catheter following closure of wound. Post-operatively, patients received boluses of 40ml ropivacaine 0.2% via the catheter using a mechanical McKinley 595 pump 4 hours after leaving theatre, at 22:00 and 08:00 on post-operative day one.
A single intravenous administration of up to 2.1 × 1014 vg/kg of ROCTAVIAN in immunocompetent male mice with intact coagulation (CD1 mice), followed by an observation period of up to 26 weeks, showed dose-dependent toxicities in the heart, lung, thymus, and epididymis. At dose levels of 6.5 × 1013 vg/kg and higher, histopathologic findings in the heart included minimal to moderate epicardial hemorrhage, myocardial necrosis, fibrosis, inflammation, and vascular/perivascular necrosis, minimal to mild mesothelial hypertrophy/hyperplasia, fibroplasia, myocardial atrophy, and vascular/perivascular mixed cell infiltrates. Lung findings included moderate to marked hemorrhage, minimal to mild edema, vascular/perivascular necrosis, and mesothelial hypertrophy. Additional ROCTAVIAN-related findings included mild fibrosis, hemorrhage, and pigmented macrophages in the epididymis, and moderate to marked hemorrhage and hypocellularity of the thymus. ROCTAVIAN-related mortality, adverse clinical observations, and changes in gross pathology were observed at dose levels of 6.5 × 1013 vg/kg and higher, and were associated with fibrosis, hemorrhage, and necrosis in the heart.

In a toxicology study conducted in adult male nonhuman primates with a duration of 3 months, single intravenous administration of ROCTAVIAN at dose levels of 1.6 × 1013 vg/kg and 5.4 × 1013 vg/kg resulted in a dose-dependent prolongation of activated partial thromboplastin time (APTT). The transient APTT prolongation in a subset of nonhuman primates was temporally associated with an immune response to hFVIII-SQ protein. At 3 months post-administration, histopathology findings included minimal to mild mononuclear/mixed infiltration in the lungs.