anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Immune-mediated liver damage is the driver of disease progression in patients with chronic hepatitis B virus (HBV) infection. Liver damage is an Ag-independent process caused by bystander activation of CD8 T cells and NK cells. How bystander lymphocyte activation is initiated in chronic hepatitis B patients remains unclear. Periods of liver damage, called hepatic flares, occur unpredictably, making early events difficult to capture. To address this obstacle, we longitudinally sampled the liver of chronic hepatitis B patients stopping antiviral therapy and analyzed immune composition and activation using flow cytometry and single-cell RNA sequencing. At 4 wk after stopping therapy, HBV replication rebounded but no liver damage was detectable. There were no changes in cell frequencies at viral rebound. Single-cell RNA sequencing revealed upregulation of IFN-stimulated genes (ISGs) and proinflammatory cytokine migration inhibitory factor (MIF) at viral rebound in patients that go on to develop hepatic flares 6-18 wk after stopping therapy. The type I IFN signature was only detectable within the liver, and neither IFN-α/β or ISG induction could be detected in the peripheral blood. In vitro experiments confirmed the type I IFN-dependent ISG profile whereas MIF was induced primarily by IL-12. MIF exposure further amplified inflammatory cytokine production by myeloid cells. Our data show that innate immune activation is detectable in the liver before clinically significant liver damage is evident. The combination of type I IFN and enhanced cytokine production upon MIF exposure represent the earliest immunological triggers of lymphocyte bystander activation observed in hepatic flares associated with chronic HBV infection.
Patients who are enrolled and randomized to the Epoetin arm will remain on their current dose and frequency. After the first hemoglobin (Hb) measurement the study algorithm will be used to guide anemia management. The subjects in this arm will remain on epoetin for the required run-in phase followed by the 12 month active phase.
In this research, we conducted hierarchical multiple regression and complex sample general linear model (CSGLM) to expand knowledge on factors contributing to mental distress, particularly from a geographic perspective. Based on the Getis-Ord G* hot-spot analysis, geographic distribution of both FMD and insufficient sleep showed several contiguous hotspots in southeast regions. Moreover, in the hierarchical regression, even after accounting for potential covariates and multicollinearity, a significant association between FMD and insufficient sleep was found, explaining that mental distress increases with increasing insufficient sleep (R2 = 0.835). In the CSGLM, a R2 value of 0.782 indicated that the CSGLM procedure provided concrete evidence that FMD was significantly related to sleep insufficiency even after taking complex sample designs and weighting adjustments in the BRFSS into account. This geographic association between FMD and insufficient sleep based on cross-county study has not been reported before in the literature. These findings suggest a need for further investigation on geographic disparity on mental distress and insufficient sleep and have novel implications in our understanding of the etiology of mental distress.
Respiratory viral infections, including respiratory syncytial virus (RSV), parainfluenza viruses and type A and B influenza viruses, can have severe outcomes. Bacterial infections frequently follow viral infections, and influenza or other viral epidemics periodically have higher mortalities from secondary bacterial pneumonias. Most secondary bacterial infections can cause lung immunosuppression by fatty acid mediators which activate cellular receptors to manipulate neutrophils, macrophages, natural killer cells, dendritic cells and other lung immune cells. Bacterial infections induce synthesis of inflammatory mediators including prostaglandins and leukotrienes, then eventually also special pro-resolving mediators, including lipoxins, resolvins, protectins and maresins, which normally resolve inflammation and immunosuppression. Concurrent viral and secondary bacterial infections are more dangerous, because viral infections can cause inflammation and immunosuppression before the secondary bacterial infections worsen inflammation and immunosuppression. Plausibly, the higher mortalities of secondary bacterial pneumonias are caused by the overwhelming inflammation and immunosuppression, which the special pro-resolving mediators might not resolve.
ISP includes 6-sessions of individual supportive psychotherapy and includes components of genuineness, unconditional positive regard, and empathic understanding through reassurance, explanation, guidance, suggestion, encouragement, affecting changes in patient's environment, and permission for catharsis. ISP emphasizes maintaining focus on the cancer experience, supporting participants in the "here and now," fostering expression of emotion and discussion of difficult topics, and creating a sense of being understood.
This study will include 70 patients diagnosed with schizophrenia, taking either risperidone, olanzapine or haloperidol, and 20 healthy control subjects. Each subject will undergo a 4 hour glucose tolerance test. In addition, there will be a small project within the overall study to measure the effects of risperidone and olanzapine on glucose regulation as the individuals switch from their prior treatment with a conventional antipsychotic medication to either risperidone or olanzapine. Ten subjects will be studied on a typical neuroleptic at baseline then switched over a one week period to risperidone or olanzapine. The participants will be evaluated at 1 week, 4 weeks, and 12 weeks, prospectively. Each evaluation will consist of a 4 hour glucose tolerance test.
Gestational diet manipulation can lead to inadequate fetal nutrient supply resulting in low birth weight, limited postnatal growth, and consequently, reduced reproductive performance in the progeny. However, effects of short-term maternal pre-conceptional dietary manipulation on postnatal growth and reproductive parameters of male offspring in large animals remains unexplored. To determine these consequences, female crossbred (Polypay x Dorset) sheep were allocated to three groups (n = 33/group) of dietary manipulation for 21 days prior to mating under the following conditions: (1) control at 100 % of maintenance energy requirements (40 Kcal of metabolizable energy/kg body weight [BW]), (2) undernutrition (UN) at 50 % of Control intake, and (3) overnutrition (ON) at 200 % of maintenance energy. Singleton ram lambs (UN:9; C:12; ON:6) were monitored from birth until 8 months of age, including birth weight, weekly weights, weight gain, body mass index (BMI), and circulating testosterone. After weaning, monthly scrotal circumference and subcutaneous fat depth were measured. Semen morphology and motility were evaluated at 7 and 8 months of age. Birth weight, weight gain, and BMI at birth and weaning were not significantly different among nutritional treatments. None of the pre-conceptional diets affected body weight change from weaning until 36 weeks of age, BMI, fat depth, or scrotal circumference across the experiment. A sustained rise in plasma testosterone concentrations was detected when ram lambs were, on average, 82 days old and 37 kg. Both testosterone concentrations and scrotal circumference were positively correlated to body weight regardless of treatment group. In addition, seminal parameters did not differ among treatments, but a transient increase in plasma testosterone at 18 weeks of age was observed in ON ram lambs compared to control rams. In conclusion, birth weight, growth indices, and seminal parameters in singleton rams are resilient features in the progeny upon maternal pre-conceptional dietary manipulation in sheep.
BACKGROUND: The development of clinical guidelines aimed at GPs is a key strategy to improving the management of chronic kidney disease (CKD). In 2019, the first CKD guideline aimed specifically at GPs practicing in Germany was published by the German College of General Practitioners and Family Physicians (DEGAM.) AIMS: The aim of this study is to identify the barriers and enablers for the implementation of this guideline. The results of this project, together with quantitative evaluation against quality indicators for CKD in primary care will inform an update to the guideline.
METHODS: We performed 17 semi-structured interviews with GPs practicing in Berlin and Brandenburg. Transcripts were analysed using qualitative content analysis as described by Mayring.
RESULTS: We found that the perception of low clinical priority of CKD compared to other chronic diseases, opportunity cost of using guidelines, as well as poor patient understanding were significant barriers. GPs expressed that improved graphic design or integration of guideline recommendations in clinical decision support systems were enabling factors. Clinical problems concerning CKD were mostly solved by recourse to informal communication with specialists. GPs reported that they rarely consulted CKD guidelines as an aide to clinical decision making.
CONCLUSION: The most significant barrier to use was that guidelines were not used as step-by-step decision aide in consultations with patients. Our analysis suggests that informal contact between primary and secondary care is significant conduit for evidence-based information on CKD in German primary care. Implementation projects should support the development of these relationships.
INTRODUCTION: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system.
METHODS: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences.
RESULTS: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%).
CONCLUSIONS: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.
A system and method for providing a radiological viewing station system customer with a recommended radiological viewing station and/or radiological viewing station configuration. The recommended radiological viewing station being established by a customer's responses to a plurality of questions. The system has a product selector file and a product configuration file. The product selector file provides a query page with the plurality of questions to be answered by the customer. The product configuration file having a plurality of predicted system values. A Java applet being used to compare the customer's responses to the plurality of questions to the predicted values. The product configuration file supplying a results page with the recommended system.
Participants will receive placebo intravenously at Week 0 followed by placebo subcutaneously at Weeks 8 and 16. At week 24 participants will receive ustekinumab SC q8w up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up.
The deep brain stimulation device will be set to a frequency of 6 Hz and will stimulate the sensorimotor region, acting as an anatomical control. If differential activation of the associative and sensorimotor STN networks is not feasible, dorsal stimulation is employed.
The present invention discloses collagen-synthetic polymer matrices which are prepared using a multiple step reaction. The first step of the reaction generally involves reacting collagen with a functionally activated synthetic hydrophilic polymer to form a collagen-synthetic polymer matrix. The synthetic hydrophilic polymer may be mono- or multifunctionally activated, but is preferably difunctionally activated, resulting in the formation of a crosslinked collagen matrix. The second step comprises modifying the collagen-synthetic polymer matrix according to one or more of the following methods: further crosslinking the matrix using a multifunctionally activated synthetic polymer, conjugating the matrix using a monofunctionally activated synthetic polymer, coupling biologically active molecules or glycosaminoglycans to the matrix, crosslinking the matrix using conventional chemical crosslinking agents, or modifying the collagen in the matrix by means of various chemical reactions. An optional third step may include further modification of the collagen-synthetic polymer matrix by covalently binding, for example, biologically active molecules or glycosaminoglycans to the matrix by means of available active groups on the synthetic hydrophilic polymers. Collagen-synthetic polymer matrices prepared according to the methods of the present invention have very low immunogenicity and can therefore be used to prepare biocompatible implants for use in a variety of medical applications. <IMAGE>
Participants receive MK-3475A (pembrolizumab Conc1 \[dose 2\] + MK-5180) SC on Day 1 of Cycles 1 to 35 without background standard of care (SOC) chemotherapy. A cycle is 21 days.
Drug: palifosfamide-tris in combination with carboplatin and etoposide palifosfamide-tris: 130 mg/m2/day 3 days every 21 days for a max of 6 cycles. carboplatin: AUC 4 mg/mL/min 1 day every 21 days for a max of 6 cycles. etoposide: 100 mg/m2/day 3 days every 21 days for a max of 6 cycles.
Participants in this group will be asked to download and install an app onto their own smartphones. After that, they will be asked to complete a sampling protocol consisting of 6 consecutive days, once a month for 6 months. During the 6 assessment days, participants will be required to complete the Edinburgh Postnatal Depression Scale, 5 momentary questions on a 5-point pictorial scale, and 2 contextual questions.
Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (β = -0.91 yr), and this was more evident among males (β = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.
Novel immunomodulatory methods for both the prevention and treatment of type I diabetes mellitus are provided. These methods comprise the administration of doses containing measured amounts (preferably superphysiologic amounts) of an adjuvant free hormonally ineffective insulin related polypeptide to the patient. Preferably this administration is carried out on a schedule designed to induce apoptosis, anergy, or other modulation of the autoimmune activity of T cells reactive with at least one epitope of the hormonally ineffective insulin related polypeptide. The hormonally ineffective insulin related polypeptide is preferably selected from the group consisting of pre-pro insulin, proinsulin, denatured insulin, insulin chain B, insulin chain A, and insulin chain C, either as whole polypeptides or fragments of these polypeptides. Combinations of these polypeptides may also be administered as long as their combination does not generate a hormonally effective insulin polypeptide. The administration of hormonally ineffective insulin related polypeptides in accordance with the invention results in beneficial effects on the development and severity of type I diabetes.
AIM: To elucidate the biological functionality and regulatory mechanisms of GdX in breast cancer (BC).
METHODS: The examination of GdX expression in human BC tissues and cell lines was conducted through immunohistochemical (IHC) and Western blot. Cell proliferation capacity was assessed via the CCK-8 and colony formation assay, while cell migration was determined through the wound healing assay. The expression levels of BCL-XL, Cyclin D1, and C-myc gene were quantified using RT-qPCR and Western blot. In vivo tumor growth was evaluated in nude mice xenografted with MDA-MB-231 cells overexpressing GdX, and a mouse model with GdX-deficient BC was established to observe the impact of GdX on BC formation and metastasis. Dual-luciferase reporter assay and immunofluorescence were employed to confirm the interaction between GdX and STAT3. Western blot was employed to validate the influence of GdX overexpression on the phosphorylation process of STAT3.
RESULTS: GdX exhibited low expression in the cancer tissues of BC patients and cell lines. MDA-MB-231 and MCF-7 cells overexpressing GdX displayed a notable reduction in proliferation and diminished migratory capabilities, accompanied by downregulated mRNA and protein expression of BCL-XL, Cyclin D1, and C-myc. In the xenograft mouse model, heightened GdX expression correlated with a decelerated in vivo tumor growth. Furthermore, in mice deteleing GdX, both the quantity and weight of tumors increased, along with evident pulmonary metastasis. Mechanistically, STAT3 emerged as a downstream target gene of GdX.
CONCLUSIONS: GdX exerts its inhibitory effects on the initiation and progression of BC by negatively modulating the phosphorylation of STAT3.
There are numerous behavioural, social and environmental factors that influence the symptomatology of a chronic health condition. These factors and how they manifest are often very specific to the individual, which creates challenges for applying macro population health approaches and insights to guide treatment. An artificial intelligence system, referred to as a non-axiomatic reasoning system (NARS), is presented. Learning in NARS is incremental and ongoing. A practical application of NARS in chronic pain management is demonstrated, as NARS can establish associations with behavioural activities that might exacerbate pain levels and revise the strengths of these associations over time. The system has potential application in any condition requiring patient-centric adaption.
Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment. After a 23 day medication washout the procedure will be repeated using placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment.
Randomly drawn from group 1 (using the Norwegian Birth Registry), but matched for time of delivery. Without history of venous thromboembolism, and with validated data from medical records.
In Part 1 (dose escalation) participants will receive intravenous (IV) infusions of ADCT-402 at escalating doses, according to a 3+3 study design. Doses will be escalated from 15 µg/kg to 200 µg/kg on Day 1 of each cycle, with cycle lengths of 3 or 6 weeks.
In this comprehensive genome-wide study, we identified and classified 83 Xylanase Inhibitor Protein (XIP) genes in wheat, grouped into five distinct categories, to enhance understanding of wheat's resistance to Fusarium head blight (FHB), a significant fungal threat to global wheat production. Our analysis reveals the unique distribution of XIP genes across wheat chromosomes, particularly at terminal regions, suggesting their role in the evolutionary expansion of the gene family. Several XIP genes lack signal peptides, indicating potential alternative secretion pathways that could be pivotal in plant defense against FHB. The study also uncovers the sequence homology between XIPs and chitinases, hinting at a functional diversification within the XIP gene family. Additionally, the research explores the association of XIP genes with plant immune mechanisms, particularly their linkage with plant hormone signaling pathways like abscisic acid and jasmonic acid. XIP-7A3, in particular, demonstrates a significant increase in expression upon FHB infection, highlighting its potential as a key candidate gene for enhancing wheat's resistance to this disease. This research not only enriches our understanding of the XIP gene family in wheat but also provides a foundation for future investigations into their role in developing FHB-resistant wheat cultivars. The findings offer significant implications for wheat genomics and breeding, contributing to the development of more resilient crops against fungal diseases.