anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The clinical syndrome of sepsis arises from severe infection, triggering an abnormal immune response that can lead to multiple organ dysfunction and ultimately the death of the host. Current therapies for sepsis are often limited in efficacy and fail to target the complex interplay of infection, inflammation and coagulation, leading to high mortality rates, which underscores the urgent need for novel therapeutics to combat sepsis. We previously identified Cath-HG, a compound capable of alleviating platelet dysfunction by suppressing GPVI-mediated platelet activation, thereby improving the survival of septic mice subjected to cecal ligation and puncture. Here, we further explored the antimicrobial, anti-inflammatory, LPS-neutralizing and anticoagulant properties of Cath-HG, as well as its protective effects in LPS-induced septic mice. Our results demonstrated that Cath-HG can bind to LPS, aggregate bacteria, and disrupt bacterial cell membranes, subsequently resulting in microbial death. Unlike most other Cathelicidins, Cath-HG displayed anticoagulation properties by regulating the enzymes plasmin, thrombin, β-tryptase, chymase and tissue plasminogen activator. In septic mice, Cath-HG provided protection against sepsis induced by LPS injection and exhibited bactericidal killing, LPS neutralization and inhibition of coagulation and MAPK signal transduction. Furthermore, Cath-HG obviously reduced the expression of pro-inflammatory cytokines and improved the pathological manifestations of tissue injury across multiple organs. Thus, Cath-HG emerges as a promising drug candidate for protecting against sepsis.
In the first 2 weeks of classical pelvic floor muscle training, individuals will perform 3 sets of 10 maximal voluntary pelvic floor muscle contraction exercises and 20 submaximal voluntary pelvic floor muscle contraction exercises per day. In every 2-week control, the number of sets will be increased by one set.
Systems and methods for enhancing the selective targeting of agents for preferential action at a target with reduced action with healthy tissue distal the target tissue. One or more agents can be combined with nano scale structures/particles for delivery to the target tissue. Appropriate bombardment with accelerated particle radiation, such as proton radiation, induces the release of the agents at the target site. Nano carriers can be combined with therapeutic and/or imaging enhancement agents. Imaging of the target tissue can provide a verification of the delivered dose of particle radiation. Nanocarriers can be provided with an outer shell selected for biocompatibility and durability in the in vivo environment and further selected to provide a feedback mechanism in the treatment environment to accelerate the release of the agent and reduce a total radiation dose needed for that release.
Cholesterol absorption plays a key role in cholesterol homeostasis and understanding the lumenal events that play key roles in absorption remain poorly understood. The aims of the present study are fourfold: 1) To determine whether previously observed effects on cholesterol absorption during bile acid feeding are related to changes in pool size and intestinal transit or meal stimulated gall bladder emptying or plasma cholecystokinin levels. 2) To determine the effect of dietary sphingomyelin on cholesterol absorption, micellar solubilization and synthesis in normal adults and to assess the effects of intralumenal cholesterol solubilization, absorption and synthesis in adults with heterozygous mdr 3 deficiency (a defect leading to low biliary phospholipid content). 3) To determine the mechanism of action of a non-ionic detergent, Pluronic F-68, by evaluating its effect on cholesterol solubilization and distribution between micelles and vesicles, on cholesterol absorption and synthesis. 4) To evaluate the intralumenal solubilization and distribution within micelles and vesicles of biliary compared to dietary cholesterol in humans and assess the impact of ezetimibe treatment on absorption of endogenous or exogenous cholesterol by assessing absorption of human contents in the biliary diverted, rat lymph fistula model. For each of these aims, subjects will be studied while consuming well-controlled diets as outpatients with a combination of human and animal techniques. Techniques employed for human studies will include state-of-the art techniques utilizing stable isotopes and isotope ratio mass spectrometry, gas chromatography. Translational studies in animals will be used including novel techniques to measure fat absorption as well as the use of the lymph fistula rat model for assessment of lipid absorption and hamsters for assessment of bile acid and sterol synthesis. Integration of animal/human techniques will provide tools to characterize the role of modifications of the intralumenal environment on cholesterol solubilization and human cholesterol absorption and synthesis.
All participants enrolled from CDEB025A2301 (n=397) who had been treated with alisporivir during the feeder study. There was no investigational treatment given to participants while enrolled in this follow-up study.
BACKGROUND: Imatinib therapy is the gold standard for the treatment of unresectable and metastatic gastrointestinal stromal tumors (GISTs). However, few studies have reported the long-term outcomes of the treatment.
METHODS: Seventy patients who underwent imatinib therapy for unresectable and metastatic GISTs were enrolled between 2001 and 2009, and follow-up data were collected until October 2023. One hundred and sixty-eight months had passed since the final enrollment. The outcome measures were patient survival and the status of GIST and imatinib therapy. The cumulative incidence of disease progression (PD) and the chronological changes in PD hazard rate (HR) were also analyzed.
RESULTS: The 5-, 10-, 15-, and 20-year overall survival rates were 64.3%, 30.0%, 16.8%, and 12.2%, respectively. Sixty of the 70 enrolled patients died before the data cutoff date: 47 (78.3%) patients died of GIST progression while the remaining 13 (21.7%) died of diseases other than GISTs. The cumulative incidence of PD logarithmically increased, and PD continued even after 10 years of treatment. PD HR decreased over time to reach the lowest value at 9.6 years after the initiation of treatment (HR 0.00027; 95% CI 0.00007-0.00174) and after that formed a small peak at 13 years (HR 0.00144; 95% CI 0.00043-0.00436).
CONCLUSIONS: Imatinib therapy showed high clinical efficacy in terms of long-term survival in GIST patients. However, patients undergoing imatinib therapy were at continuous risk of PD even after the 10-year treatment. Long-term treatment and follow-up beyond 10 years are necessary for unresectable and metastatic GIST patients.
BACKGROUND: Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization.
RESULTS: The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains.
CONCLUSION: Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.
This is an international, multi-center, open-label, prospective, phase II study designed to assess the efficacy of radiation therapy in combination with Radium-223 dichloride in patients diagnosed with CRPC and oligo metastases bone disease. All patients enrolled in this study will have signed an informed consent form (ICF) and will adhere to all inclusion and exclusion criteria.

During the treatment period, patients will be followed on an ongoing basis for safety and quality of life (QoL). Safety assessments will include the collection of all AEs of any grade, serious adverse events (SAEs), adverse event (AEs) corresponding to symptoms arising from bone metastases, laboratory values, (WHO/ECOG) performance status (PS). Documentation of the date of disease progression will be performed at intervals and imaging methods (bone scans and CR/MRI) described in the study protocol. Quality of life will be measured by patient assessment using a validated questionnaire, the Brief Pain Inventory Short Form (BPI-SF), the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C15-PAL and the EORTC QLQ- Bone Metastases (BM) 22. Follow-up assessments for safety AEs and SAEs, and the occurrence of secondary malignancies will be conducted every 3-12 months until the patient dies or until the study is terminated by the sponsor. If the patient can no longer travel to the clinical site, he will be followed up for survival only, i.e., the long term follow-up phase of the study.
Pregnancy Category C:

Risk Summary

There are no adequate and well-controlled studies of quetiapine use in pregnant women. In limited published literature, there were no major malformations associated with quetiapine exposure during pregnancy. In animal studies, embryo- fetal toxicity occurred. Quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Human Data

There are limited published data on the use of quetiapine for treatment of schizophrenia and other psychiatric disorders during pregnancy. In a prospective observational study, 21 women exposed to quetiapine and other psychoactive medications during pregnancy delivered infants with no major malformations. Among 42 other infants born to pregnant women who used quetiapine during pregnancy, there were no major malformations reported (one study of 36 women, 6 case reports). Due to the limited number of exposed pregnancies, these postmarketing data do not reliably estimate the frequency or absence of adverse outcomes. Neonates exposed to antipsychotic drugs (including quetiapine), during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Animal Data

When pregnant rats and rabbits were exposed to quetiapine during organogenesis, there was no teratogenic effect at doses up to 2.4 times the maximum recommended human dose (MRHD) for schizophrenia of 800 mg/day based on mg/m 2 body surface area. However, there was evidence of embryo-fetal toxicity, which included delays in skeletal ossification occurring at approximately 1 and 2 times the MRHD of 800 mg/day in both rats and rabbits, and an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses at approximately 2 times the MRHD. In addition, fetal weights were decreased in both species. Maternal toxicity (observed as decreased body weights and/or death) occurred at 2 times the MRHD in rats and approximately 1-2 times the MRHD (all doses tested) in rabbits. 

In a peri/postnatal reproductive study in rats, no drug-related effects were observed when pregnant dams were treated with quetiapine at doses 0.01, 0.12, and 0.24 times the MRHD of 800 mg/day based on mg/m2 body surface area. However, in a preliminary peri/postnatal study, there were increases in fetal and pup death, and decreases in mean litter weight at 3 times the MRHD.
The aim is to identify high-risk patients before the initial operation based on their immunological profile and to be able to provide them with an improved, individualised therapeutic strategy. There are already a large number of approved therapeutic options that are currently only used in revision cases because, among other things, preoperative diagnostics and prognostics are lacking. Furthermore, a sufficient preoperatively determined biomarker would form the basis for the development of new therapeutic approaches, which represent a low cost-benefit and risk-benefit ratio.

The prospective biomarker validation study is applied in a routine-adapted procedure, i.e. all visits are part of the clinical radiological and functional routine checks. Blood sampling on arrival at the hospital will be used to determine the preoperative value of CD8+TEMRA cells. The healing process will be recorded using X-ray/CT images, radiological scores and functional clinical examinations as well as the SF-36. The 1st study endpoint (delayed healing) is after 17-19 weeks postoperatively, the 2nd study endpoint (pseudarthrosis) after 34-36 weeks. The validation of the biomarker will take place in a blinded procedure, whereby the predefined threshold value of the preoperative CD8+ TEMRA cell expression will be compared with the patient's healing status.
Emergency contraception is a means by which an undesirable pregnancy may be prevented. As such, its use may be envisaged following unforeseen sexual relations, a burst condom, and a maladjusted diaphragm. Its use may also be justified following a rape and noncompliance with the dosing of oral contraceptives. The Yuzpe method is among the most common means of emergency contraception. Nonetheless, this method entails numerous side effects of which the most predominant are nausea (54-74 %) and vomiting (24-30 %). The concomitant use of a dimenhydrinate salt (100 mg) thirty to sixty minutes prior to the Yuzpe method results in either the prevention or the attenuation of the aforementioned side effects.
Participants received 160 mg of enzalutamide orally once a day during double blind period until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer. Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.
OBJECTIVES: This study aimed to elucidate the clinical characteristics and predictors of long-term postoperative urinary incontinence (PUI) after robot-assisted radical prostatectomy (RARP).
METHODS: This study included patients who underwent RARP at our institution and were stratified into PUI (≥1 pad/day) and continence (0 pad/day) groups at 60 months after RARP. A propensity score-matched analysis with multiple preoperative urinary status (Expanded Prostate Cancer Index Composite urinary subdomains, total International Prostate Symptom Score (IPSS), and IPSS-quality of life scores) was performed to match preoperative urinary status in these groups. Serial changes in urinary status and treatment satisfaction preoperatively and until 60 months after RARP were compared, and predictors of long-term PUI were assessed using multivariate logistic regression analysis.
RESULTS: A total of 228 patients were included in the PUI and continence groups (114 patients each). Although no significant difference in preoperative urinary status was observed between the two groups, the postoperative urinary status significantly worsened overall in the PUI group than in the continence group. Treatment satisfaction was also significantly lower in the PUI group than in the continence group from 12 to 60 months postoperatively. Multivariate logistic regression analysis revealed that age (≥70 years) and biochemical recurrence (BCR) were significant predictors of the long-term PUI group (p < 0.05).
CONCLUSIONS: Patients with long-term PUI had poor overall postoperative urinary status and lower treatment satisfaction than the continence group. Considering the age and risk of BCR is important for predicting long-term PUI when performing RARP.
INTRODUCTION AND HYPOTHESIS: We aimed to evaluate the outcomes, complication rates, and complication types of different labiaplasty techniques.
METHODS: In this cross-sectional retrospective study, a total of 2,594 patients who underwent surgery owing to hypertrophy or asymmetry of the labium minus were retrospectively analyzed. Data were collected by individual interviews with 43 experts from different centers. The patients were between 18 and 50 years of age. During the interview information about the presence and nature of complications, and about concomitant or revision surgeries, were gathered. The surgeons who performed these surgeries were also questioned about their training and surgical experience.
RESULTS: The most frequently observed complication was complete dehiscence, accounting for 29% of all complications. Complete dehiscence was most commonly seen after wedge resection (16 cases). The second most common complication was labium majus hematoma, accounting for 12.5% of all cases. Among the labiaplasty techniques, wedge resection had the highest complication rate at 3% (26 cases out of 753 patients). This was followed by composite labiaplasty at 1.2% (5 cases out of 395 patients), Z-plasty at 0.8% (1 case out of 123 patients), and trimming labiaplasty at 0.5% (7 cases out of 1,323 patients).
CONCLUSION: Considering the heterogeneity and low quality of the existing studies on this subject, this study provides valuable information for surgeons practicing in this field. However, further research is clearly warranted as female genital aesthetic procedures are being performed with a steadily increasing trend.
Clinical failure of arteriovenous neointimal hyperplasia (NIH) fistulae (AVF) is frequently due to juxta-anastomotic NIH (JANIH). Although the mouse AVF model recapitulates human AVF maturation, previous studies focused on the outflow vein distal to the anastomosis. We hypothesized that the juxta-anastomotic area (JAA) has increased NIH compared with the outflow vein. AVF was created in C57BL/6 mice without or with chronic kidney disease (CKD). Temporal and spatial changes of the JAA were examined using histology and immunofluorescence. Computational techniques were used to model the AVF. RNA-seq and bioinformatic analyses were performed to compare the JAA with the outflow vein. The jugular vein to carotid artery AVF model was created in Wistar rats. The neointima in the JAA shows increased volume compared with the outflow vein. Computational modeling shows an increased volume of disturbed flow at the JAA compared with the outflow vein. Endothelial cells are immediately lost from the wall contralateral to the fistula exit, followed by thrombus formation and JANIH. Gene Ontology (GO) enrichment analysis of the 1,862 differentially expressed genes (DEG) between the JANIH and the outflow vein identified 525 overexpressed genes. The rat jugular vein to carotid artery AVF showed changes similar to the mouse AVF. Disturbed flow through the JAA correlates with rapid endothelial cell loss, thrombus formation, and JANIH; late endothelialization of the JAA channel correlates with late AVF patency. Early thrombus formation in the JAA may influence the later development of JANIH.NEW & NOTEWORTHY Disturbed flow and focal endothelial cell loss in the juxta-anastomotic area of the mouse AVF colocalizes with acute thrombus formation followed by late neointimal hyperplasia. Differential flow patterns between the juxta-anastomotic area and the outflow vein correlate with differential expression of genes regulating coagulation, proliferation, collagen metabolism, and the immune response. The rat jugular vein to carotid artery AVF model shows changes similar to the mouse AVF model.
Participants received 1 or 2 doses of CUSA-081, 0.7 milligrams (mg) (0.4 units) per 2 milliliter (mL) directly into the catheter lumen. Participants received the first dose at minute (min) 0, and the second dose (if needed) at min 90.
High red and processed meat intake and genetic predisposition are risk factors of colorectal cancer (CRC). However, evidence of their independent and joint associations on the risk of colorectal neoplasms is limited. We assessed these associations among 4774 men and women undergoing screening colonoscopy. Polygenic risk scores (PRSs) were calculated based on 140 loci related to CRC. We used multiple logistic regression models to evaluate the associations of red and processed meat intake and PRS with the risk of colorectal neoplasms. Adjusted odds ratios (aORs) were translated to genetic risk equivalents (GREs) to compare the strength of the associations with colorectal neoplasm risk of both factors. Compared to ≤1 time/week, processed meat intake >1 time/week was associated with a significantly increased risk of colorectal neoplasm [aOR (95% CI): 1.28 (1.12-1.46)]. This risk increase was equivalent to the risk increase associated with a 19 percentile higher PRS. The association of red meat intake with colorectal neoplasm was weaker and did not reach statistical significance. High processed meat intake and PRS contribute to colorectal neoplasm risk independently. Limiting processed meat intake may offset a substantial proportion of the genetically increased risk of colorectal neoplasms.