anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Anxiety and depressive disorders are becoming the major psychological issue in Pakistan due to several circumstances. Social anxiety is one the prominent symbol for psychological disturbance observed in young generation. Since, other therapeutic approaches for social anxiety have not shown significant benefit regarding improvement of symptoms recovery and to avoid relapse of the symptoms, further researches needed to focus on improving post-functioning recovery. The uses of mindfulness and acceptance base group therapy manual for social anxiety has shown significantly reduce symptoms of social anxiety after the therapy in other regions of the world. In this regard the present study will help to enhance the variety of treatment plan and to evaluate the effectiveness of mindfulness in this subject. Therefore, objective of the present study is to see the feasibility and effectiveness of social anxiety in females with the help of mindfulness and acceptance based therapy. In this regard hypothesis is designed as; women in the intervention group will have significantly reduced anxiety as compared to the women in the control group . A total of 60 females in the age range of 18 to 28 ages will be recruited from Institute of professional psychology . The participants will be recruited through the administration of Mini-Social Phobia Inventory (SPIN-mini). Total of 32 participants will be randomly divided in interventions and control group will receive the intervention of ten sessions of group therapy of MABT plan. The manual group intervention will be provided as per the second edition of Mindfulness and Acceptance-Based Group Therapy for Social Anxiety Disorder: A Treatment Manual developed by Fleming, and Kocovski (2014). The intervention will consist of 10 group therapy sessions. Each session will be conducted in 120 minutes. It includes therapist manual, client handouts, and is written to be used in conjunction with The Mindfulness and Acceptance Workbook for Social Anxiety and Shyness. The treatment manual can be easily adapted for individual therapy clients.At the end scores of re-administration of the questionnaire will help to assess the outcomes of the study. Results of this intervention study will be analysed through quantities measures.
A system for utilizing diagnostics for informed vibrant constitutional guidance is disclosed. The system includes at least a server and a diagnostic engine operating on the at least a server. The diagnostic engine is configured to receive a first set of contextual information associated with a user. The diagnostic engine is also configured to generate a diagnostic output as a function of the plurality of contextual information using a trained machine-learning model. The machine-learning model may be trained using the first training data set and the second training data set. The generating the diagnostic output includes transmitting the diagnostic output to an advisor client device.
RNA drug targets are pervasive in cells but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross Linking and isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of non-coding RNAs.
Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.
The intervention period will last 4 weeks, with a periodicity of 2 weekly sessions of 30 minutes each. All interventions will take place in the sports facilities of both clubs. The interventions will be carried out by the principal investigator of the study. The 10 players assigned to the experimental group will perform plyometric exercises and will undergo dry needling of the gastrocnemius (gastrocnemius muscle) and the control group (plyometric exercises and dry needling of the gastrocnemius muscle).
A method of providing gait coaching is disclosed. Run data is received and stored regarding runs of a broad and diverse population of users, as well as a more narrow set of expert users. A gait metric model is developed for determining an ideal stride length or cadence based on pace and at least one physiological characteristic. Regression coefficients for at the model are determined based on a regression of the run data from the broad and diverse population of users. In contrast, a regression constant for the model is determined based on a regression of the run data from expert users. Using the model, an ideal stride length or cadence for a particular user on a particular run can be determined and utilized to provide useful monitoring, comparison, and feedback to the user regarding his or her stride length or cadence.
Hypoxic-ischaemic encephalopathy (HIE) is a major cause of mortality and neurodevelopmental disability, especially in low-income countries. While therapeutic hypothermia has been shown to reduce morbidity and mortality in infants with HIE, some clinical trials in low-income countries have reported an increase in the risk of mortality. We conducted a systematic review and meta-analysis of all randomized and quasi-randomized controlled trials conducted in low-income and lower-middle-income countries that compared cooling therapy with standard care for HIE. Our primary outcome was composite of neonatal mortality and neurodevelopmental disability at 6 months or beyond. The review was registered with PROSPERO (CRD42022352728). Our review included 11 randomized controlled trials with 1324 infants with HIE. The composite of death or disability at 6 months or beyond was lower in therapeutic hypothermia group (RR 0.78, 95% CI 0.66-0.92, I2 = 85%). Neonatal mortality rate did not differ significantly between cooling therapy and standard care (RR 0.92, 95% CI 0.76-1.13, I2 = 61%). Additionally, the cooled group exhibited significantly lower rates of neurodevelopmental disability at or beyond 6 months (RR 0.34, 95%CI 0.22-0.52, I2 = 0%). Our analysis found that neonatal mortality rate did not differ between cooled and noncooled infants in low- and lower-middle-income countries. Cooling may have a beneficial effect on neurodevelopmental disability and the composite of death or disability at 6 months or beyond.
Diabetic retinopathy (DR) is a blinding disease caused by diabetes, characterized by neovascularization of the retina. The aim of this study was to investigate the roles of epidermal growth factor-like structural domain 7 (EGFL7) on human retinal vascular endothelial cells (HRECS) and retinas from rats with DR. An in vitro model of DR was established through culturing HRECS in high glucose. The in vivo model of DR was established by injecting SD rats with streptozotocin (STZ) to induce diabetes. The differences in the expressed levels of EGFL7, PI3K, AKT, P-AKT and VEGFA in high-glucose cultured cells and retinal tissues of diabetic rats were detected in compared to those in the control group. Stable EGFL7 knockdown cell lines were generated by transfecting HRECS with lentiviral vectors and the effects of EGFL7 knockdown on angiogenesis, cell migration and proliferation were investigated. The results showed that EGFL7, PI3K, P-AKT and VEGFA was increased in cells and tissues under high glucose conditions. Knockdown of EGFL7 downregulated the proliferation, migration and angiogenesis capacity of HRECS, and blocked the PI3K/AKT/VEGFA signaling pathway. Furthermore, overexpression of PI3K reversed the effects of EGFL7 inhibition. These findings provide new ideas for the treatment of neovascularisation in DR.
Participants will receive the same exercise program at the Exercise Only group + 1) one-on-one telephone-based counselling (10 x 30-minute telephone: weeks 1, 2, 3, 4, 5, 6, 8, and 12 (during the exercise program) and at weeks 20,28 (post-exercise program booster sessions)); 2) supportive software on smart-phone devices (the HealthCoach program), 3) use of Fit-bit and corresponding software. The iMOVE intervention was designed to enhance sustained behavior change. The theoretical constructs employed are based on promoting motivation and establishing: a) exercise self-efficacy, b) social support for exercise and c) positive exercise-induced feelings during the acute intervention (12 weeks) and post-exercise program period (6 months).
UNLABELLED: Neutrophils are a highly heterogeneous cellular population. However, a thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing of human and murine datasets, both publicly available and independently generated, to identify neutrophil transcriptomic subtypes and developmental lineages in health and malignancy. Datasets of lung, breast, and colorectal cancer were integrated to establish and validate neutrophil gene signatures. Pseudotime analysis was used to identify genes driving neutrophil development from health to cancer. Finally, ligand-receptor interactions and signaling pathways between neutrophils and other immune cell populations in primary colorectal cancer and metastatic colorectal cancer were investigated. We define two main neutrophil subtypes in primary tumors: an activated subtype sharing the transcriptomic signatures of healthy neutrophils; and a tumor-specific subtype. This signature is conserved in murine and human cancer, across different tumor types. In colorectal cancer metastases, neutrophils are more heterogeneous, exhibiting additional transcriptomic subtypes. Pseudotime analysis implicates IL1β/CXCL8/CXCR2 axis in the progression of neutrophils from health to cancer and metastasis, with effects on T-cell effector function. Functional analysis of neutrophil-tumoroid cocultures and T-cell proliferation assays using orthotopic metastatic mouse models lacking Cxcr2 in neutrophils support our transcriptional analysis. We propose that the emergence of metastatic-specific neutrophil subtypes is driven by the IL1β/CXCL8/CXCR2 axis, with the evolution of different transcriptomic signals that impair T-cell function at the metastatic site. Thus, a better understanding of neutrophil transcriptomic programming could optimize immunotherapeutic interventions into early and late interventions, targeting different neutrophil states.
SIGNIFICANCE: We identify two recurring neutrophil populations and demonstrate their staged evolution from health to malignancy through the IL1β/CXCL8/CXCR2 axis, allowing for immunotherapeutic neutrophil-targeting approaches to counteract immunosuppressive subtypes that emerge in metastasis.
The recommended starting dose of Droxidopa capsules is 100 mg, taken orally three times daily: upon arising in the morning, at midday, and in the late afternoon at least 3 hours prior to bedtime (to reduce the potential for supine hypertension during sleep). Administer Droxidopa capsules consistently, either with food or without food. Take Droxidopa capsule whole. Titrate to symptomatic response, in increments of 100 mg three times daily every 24 to 48 hours up to a maximum dose of 600 mg three times daily (i.e., a maximum total daily dose of 1,800 mg).

Monitor supine blood pressure prior to initiating Droxidopa capsules and after increasing the dose. 

Patients who miss a dose of Droxidopa should take their next scheduled dose.
Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.
Group 3. Stenting of the common iliac vein with or without gonadal veins embolization This group includes patients who underwent isolated iliac vein stenting or iliac vein stenting combined with gonadal vein embolization.
RATIONALE: In chronic obstructive pulmonary disease (COPD), accurately estimating lung function from electronic health record (EHR) data would be beneficial but requires addressing complexities in clinically obtained testing. This study compared analytic methods for estimating rate of forced expiratory volume in one second (FEV1) change from EHR data.
METHODS: We estimated rate of FEV1 change in patients with COPD from a single centre who had ≥3 outpatient tests spanning at least 1 year. Estimates were calculated as both an absolute mL/year and a relative %/year using non-regressive (Total Change, Average Change) and regressive (Quantile, RANSAC, Huber) methods. We compared distributions of the estimates across methods focusing on extreme values. Univariate zero-inflated negative binomial regressions tested associations between estimates and all-cause or COPD hospitalisations. Results were validated in an external cohort.
RESULTS: Among 1417 participants, median rate of change was approximately -30 mL/year or -2%/year. Non-regressive methods frequently generated erroneous estimates due to outlier first measurements or short intervals between tests. Average change yielded the most extreme estimates (minimum=-3761 mL/year), while regressive methods, and Huber specifically, minimised extreme estimates. Huber, Total Change and Quantile FEV1 slope estimates were associated with all-cause hospitalisations (Huber incidence rate ratio 0.98, 95% CI 0.97 to 0.99, p<0.001). Huber estimates were also associated with smoking status, comorbidities and prior hospitalisations. Similar results were identified in an external validation cohort.
CONCLUSIONS: Using EHR data to estimate FEV1 rate of change is clinically applicable but sensitive to challenges intrinsic to clinically obtained data. While no analytic method will fully overcome these complexities, we identified Huber regression as useful in defining an individual's lung function change using EHR data.
###  Risk Summary

There are no available human data for the use of bepotastine besilate ophthalmic solution during pregnancy to inform any drug-associated risks. 

Oral administration of bepotastine besilate to pregnant rats or rabbits during organogenesis or during the pre/postnatal period did not produce adverse embryofetal or offspring effects at clinically relevant systemic exposures. Maternal toxicity was observed in the rabbits at the lowest dose administered, 20 mg/kg/day (215 times the maximum recommended human ophthalmic dose, RHOD, on a mg/m2 basis) [see Data]. 

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

###  Data

#### Animal Data 

In embryofetal development studies, oral administration of bepotastine besilate to pregnant rabbits throughout organogenesis did not produce teratogenic effects at maternal doses up to 500 mg/kg/day (approximately 5400 times the maximum RHOD, on a mg/m2 basis). A maternal no observed adverse effect level (NOAEL) was not identified in this study due to spontaneous abortion observed at the lowest dose tested, 20 mg/kg/day (approximately 215 times higher than the maximum RHOD, on a mg/m2 basis). Oral administration of bepotastine besilate to pregnant rats throughout organogenesis produced skeletal anomalies at 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis), a dose that also produced maternal toxicity and lethality. No teratogenic effects were observed in rats at maternal doses up to 200 mg/kg/day (corresponding to an estimated blood plasma concentration 3300 times higher than that anticipated in humans at the maximum RHOD). A maternal NOAEL was observed at 10 mg/kg/day (54 times higher than the maximum RHOD, on a mg/m2 basis). Following a single 3 mg/kg oral dose in rats (16 times higher than the maximum RHOD, on a mg/m2 basis), the concentration of radio-labeled bepotastine besilate was similar in fetal liver and maternal blood plasma. The concentration in other fetal tissues was one-third to one-tenth the concentration in maternal blood plasma.

In a pre/postnatal development study, oral administration of bepotastine besilate to rats during the perinatal and lactation periods produced an increase in stillbirths and decreased growth and development in offspring at a maternal dose of 1000 mg/kg/day (5400 times higher than the maximum RHOD, on a mg/m2 basis). There were no observed adverse effects on offspring of rats treated with 100 mg/kg/day (540 times higher than the maximum RHOD, on a mg/m2 basis). Effects on parturition and maternal lethality were observed at 100 mg/kg/day and 1000 mg/kg/day, respectively. A maternal NOAEL was observed at 10 mg/kg/day (54 times higher than the maximum RHOD, on a mg/m2 basis).
The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. There is no conventional treatment available to correct this condition. Our research group has been developing an adeno-associated virus vector based on the hypothesis that this vector is capable of safely transferring the human aquaporin-1 (hAQP1) cDNA gene to parotid glands of adult patients with IR-induced salivary hypofunction, resulting in an elevated salivary output. Human AQP1 is a plasma membrane protein that facilitates water movement across lipid bilayers. Minipig studies have shown that the AAV2hAQP1 strategy for restoring salivary flow to IR-damaged salivary glands is effective without untoward effects after salivary gland delivery. As a proof of concept that AQP1 would restore saliva flow in a human population, we recently completed a phase 1 clinical trial (06-D-0206) using an Adenovirus-based vector encoding AQP1 to a single previously irradiated parotid gland in eleven patients using an open label, single dose, dose-escalation design. All patients tolerated vector delivery and study procedures well and positive objective and subjective responses were seen in five patients, all at doses \<5.8 times10(9) vp/gland. At higher doses the patients possibly initiated an immune response to the vector and no improvement in gland function was observed. These findings have encouraged us to pursue studies with AAV2 based vectors, which have demonstrated lower immunogenicity and more stable expression compared with adenoviral vectors. The purpose of this clinical protocol is to test the safety of AAV2hAQP1, with some measures of efficacy, in adult patients with established IR-induced parotid gland hypofunction. The targeted tissue site for the AAV2hAQP1 vector in the proposed study is a single parotid gland. In this Phase 1 dose-escalation study, safety will be evaluated using conventional clinical and immunological parameters. The primary outcome measure for biological efficacy will be parotid gland salivary output.