anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVE: FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism.
METHODS: Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis.
RESULTS: The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA+HLA-DR+, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment.
CONCLUSIONS: We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.
The present invention relates to a health capsule, health chewable tablets and medicinal powder containing haw flavone with health care functions by using haws as major raw material and the preparation method of the health capsule, the health chewable tablets and the medicinal powder. The haw is a deciduous plant of the same source of medicine and food in a temperate zone. The haw has rich nutrition and contains protein, fat, carbohydrate, calcium, phosphorus, ferrum, carotene, thioflavine S, riboflavin, nicotinic acid, maslinic acid, citric acid, a vitamin C, etc. The haw also contains biologic flavonoid with the abbreviation of the haw flavone which can not be self synthetized in a human body. The haw flavone is a substance which has no toxic or side effect, is beneficial to heart health and has the functions of reducing blood lipid, strengthening hearts, preventing atherosclerosis, etc. The present invention has the preparation method comprising: the haws are mashed, sieved, adjusted, dried in a vacuum freeze mode, crushed, sieved, encapsulated or tabletted or prepared into powder health functional food rich in the haw flavone after boiled.
The current healthcare delivery system for patients with acute musculoskeletal injury is failing. Current rehabilitation management of acute musculoskeletal injury typically includes physical therapy, focused on management of impairments, with an eventual transition to functional activities and release to prior level of function. At that point, formal physical therapy is often discontinued, despite the knowledge that a high percentage of patients fail to maintain preinjury level of activity and often reduce participation in regular physical activity. Further, for those who attempt to return to prior levels of pivoting and cutting activities, there is a high second injury rate. The long-term human experience is compromised by the current model of care which terminates at the point of transition to activity. This model of care fails to meet the continued needs of these patients and may result in long term deficits and potential disability. Extended care models include intermittent follow up visits after discharge from an acute episode of care and have been efficacious and cost effective in some patient populations with musculoskeletal conditions. Specifically, a type of extended care model, labeled "booster sessions," represents an opportunity to provide structured, intermittent care to assist in a smooth transition back to function, following an acute episode of care and promote a healthier life outcome. This perspective review will discuss the opportunity to transform acute musculoskeletal care to booster visit care model in an attempt to develop a more efficacious and cost-effective system of care which could be generalizable to all musculoskeletal conditions.
Tramadol and venlafaxine share similar pharmacological characteristics that may allow for overlapping therapeutic indications for them. The objective of this study was to compare the efficacy of venlafaxine and naltrexone in the treatment of tramadol abuse. This comparative trial included 95 patients with tramadol abuse who were detoxified for 2 weeks. Twenty-eight participants underwent the maintenance phase, while the remaining participants (n = 67) dropped out. The patients were randomized to use 50 mg/day of naltrexone or 225 mg/day of venlafaxine for 8 weeks. All participants were interviewed using SCID-I (DSM-IV-TR) criteria for diagnosing substance use and other psychiatric disorders. The proportion of relapsed patients was comparable between the naltrexone and venlafaxine groups (29.4% vs. 30.4%, P  = 0.9). However, participants in the venlafaxine group stayed in treatment longer than participants in the naltrexone group, and the difference was significant (22.9 ± 7.89 days vs. 16.9 ± 3.4 days, P = 0.01). Only psychiatric comorbidity was found to be significantly associated with retention in treatment (80% vs. 22%, P  = 0.005). Venlafaxine is as effective as naltrexone in preventing relapse in patients with tramadol abuse. Venlafaxine was more effective than naltrexone in treatment retention.
BACKGROUND: Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS.
METHODS: A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health's EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores-SHapley Additive exPlanation (SHAP) values-for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation.
RESULTS: Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795-0.840), sensitivity of 0.766 (95% CI 0.743-0.790), F-score of 0.761 (95% CI 0.744-0.778), AUC of 0.808 (95% CI 0.791-0.825), and accuracy of 0.775 (95% CI 0.759-0.790).
CONCLUSIONS: This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs.
To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.
PROBLEM TO BE SOLVED: To obtain a new anti-leukotriene, antihistamine, antiallergic and antiinflammatory composition useful for the treatment of an allergic disease such as rhinitis, bronchitis, asthma or hives by compounding a nonsteroidal antiinflammatory sulfonanilide with a second-generation antihistamine agent. SOLUTION: This composition is obtained by compounding a nonsteroidal antiinflammatory sulfonanilide such as nimeulide or its salt and a second-generation antihistaminic agent (H1 -blocker) such as cetirizine in a base and a diluting agent. The composition contains preferably 1-53 pts.wt. of nimesulide, 0.3-3.3 pts.wt. of cetirizine and 44-98.5 pts.wt. of the base and diluting agent. It may be obtained by blending nimesulide and cetirizine homogeneously, and passing the mixture through a fine-mesh sieve to reduce the content of fine-sized powder. When the composition is administered in the form of capsule, the above- mentioned powder may be gelatin-capsulated after it has been blended with a diluent at a temperature of 25±2 deg.C and a relative humidity of 50±5%.
Stroke causes pronounced and widespread slowing of neural activity. Despite decades of work exploring these abnormal neural dynamics and their associated functional impairments, their causes remain largely unclear. To close this gap in understanding, we applied a neurophysiological corticothalamic circuit model to simulate magnetoencephalography (MEG) power spectra recorded from chronic stroke patients. Comparing model-estimated physiological parameters to those of controls, patients demonstrated significantly lower intrathalamic inhibition in the lesioned hemisphere, despite the absence of direct damage to the thalamus itself. We hypothesized that this disinhibition could instead be related to secondary degeneration of the thalamus, for which growing evidence exists in the literature. Further analyses confirmed that spectral slowing correlated significantly with overall secondary degeneration of the ipsilesional thalamus, encompassing decreased thalamic volume, altered tissue microstructure, and decreased blood flow. Crucially, this relationship was mediated by model-estimated thalamic disinhibition, suggesting a causal link between secondary thalamic degeneration and abnormal brain dynamics via thalamic disinhibition. Finally, thalamic degeneration was correlated significantly with poorer cognitive and language outcomes, but not lesion volume, reinforcing that thalamus damage may account for additional individual variability in poststroke disability. Overall, our findings indicate that the frequently observed poststroke slowing reflects a disruption of corticothalamic circuit dynamics due to secondary thalamic dysfunction, and highlights the thalamus as an important target for understanding and potentially treating poststroke brain dysfunction.
Many individuals with psychotic disorders experience poor functional outcomes such as lower quality of life, lower levels of education, and lower life expectancy. Comorbid mental disorders, such as posttraumatic stress disorder and related posttraumatic stress symptoms tend to aggravate psychotic symptoms and, as a result, worsen functional outcomes. Further, emotion regulation and interpersonal functioning are generally impaired in individuals with psychotic disorders and histories of childhood trauma, and preliminary evidence suggests that these impairments may mediate the relationship between childhood trauma and psychotic symptom severity. Despite the high levels of trauma observed in psychotic populations, the last decade has seen only a modest increase in the number of trials examining the efficacy of trauma interventions in this population. Further, given the initial distress, destabilization, and increased vulnerability that may occur when first engaging in trauma-focused intervention, it has been argued that in those with psychotic disorders, stabilizing/grounding interventions may be a necessary fist step prior to engagement in trauma therapy. This study will thus assess whether the Social Skills and Emotion Regulation Training (SSERT) for Trauma in Psychosis is feasible and acceptable to offer as a preparatory intervention, and will examine its preliminary effect on emotion regulation, interpersonal functioning, and other functional outcomes. SSERT proposes a single-arm baseline with post-intervention design. We will recruit 20 participants with a psychotic disorder, a history of trauma, and an impairment in interpersonal functioning and/or emotion regulation. The intervention will consist of nine weekly hour-long individual sessions and one final 90-minute session. The feasibility of SSERT will be assessed by examining the profile or safety of the study (including whether there are any adverse events reported), the participant flow (missed sessions, attrition rates, retention/completion rates), and through both standardized and qualitative items assessing therapist feedback. The acceptability of SSERT will be assessed subjectively, specifically though participant responses on therapy satisfaction, therapeutic alliance, and motivation for therapy questionnaires. Qualitative analyses will identify common themes and assess participant comments. We expect that SSERT will be both feasible and acceptable to administer to this population. Any expectations regarding the intervention's effect in improving emotion regulation, interpersonal functioning, and other functional outcomes is exploratory. Overall, SSERT may help people with psychotic disorders to better understand how the experience and effect of trauma impacts their relationships and emotion management. The intervention may also help to improve functional outcomes and relationship quality by teaching emotion regulation and grounding strategies, and through learning to become more engaged and flexible in relationships.
PURPOSE: To produce an aloe juice by extracting an aloe gel containing substantially no anthraquinonc from a leaf of aloe plant. CONSTITUTION: A leaf of an aloe plant is washed with an antiseptic solution (e.g. an aqueous solution of calcium hypochlorite) to remove a soil and bacteria on the surface of the leaf. A juice rich in anthraquinone is obtained by removing the tip part and base part of the washed leaf, and leaving and allowing the removed leaf to drain the juice. Further, the resultant leaf is taken out from the solution, and hull of the leaf is removed to provide an aloe gel fillet. The aloe gel fillet is ground and homogenized to provide the objective aloe juice containing substantially no anthraquinone, that is about <0.001 wt.% thereof. Preferably, a fibrous material is removed from the aloe juice by filtration. The aloe juice is formulated with many kinds of products for internal use and external use, e.g. cosmetics, health foods and drinks, medicines.
Immune checkpoint inhibitors against Programmed Cell Death Protein 1/Programmed Cell (PD-1/PD-L1) and CTLA-4/B7 axes have had limited success in hematologic malignancies, requiring the need to explore alternative targets such as T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/CD155 to improve durable clinical responses. We undertook this study to investigate the expression profile of TIGIT such that the potential efficacy of TIGIT blockade could be mapped among lymphoma subtypes. We validated an immunohistochemical assay for TIGIT and evaluated its expression in lymphoma and tumor microenvironment (TME) cells in 661 lymphoma/leukemia biopsies. Multiplex immunofluorescence was used for correlation with normal TME cell subsets. Tumor or TME TIGIT-positivity was defined as moderate to strong membrane staining in at least 10% of tumor or TME cells, respectively. TME TIGIT expression was correlated with overall survival and progression-free survival and comparison with PD-L1 expression. In most cases, lymphoma cells were TIGIT-negative except for angioimmunoblastic and peripheral T-cell lymphomas, which showed 91% and 47% positivity, respectively. A high proportion of small B-cell lymphoma and anaplastic large cell lymphoma cases had TIGIT-positive TME cells. Chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TIGIT-negative TME cells showed significantly shorter overall survival ( P =0.04). No other statistically significant differences were found. When TIGIT was expressed in TME cells, there were a comparable number of TIGIT-positive only and dual TIGIT/PD-L1 positive cases except for more TIGIT-positive only cases in CLL/SLL. TIGIT expression shows distinctive profiles among lymphoma subtypes. Chronic lymphocytic leukemia/small lymphocytic lymphoma and anaplastic large cell lymphoma demonstrated high TME TIGIT expression compared with PD-L1, with a high proportion of dual TIGIT and PD-L1-positivity. Our results are likely to contribute to the design and correlative study of therapeutic response in clinical trials targeting TIGIT alone or in combination with PD1/PDL1.
PURPOSE:To obtain a separating agent, consisting of a cation exchange resin, calcium phosphate or a solid acid and capable of effectively separating the titled antigen useful as a vaccine raw material. CONSTITUTION:A separating agent consisting of a cation exchange resin, calcium phosphate or a solid acid and useful for separating HBs antigen and HBe antigen. A separating agent having preferably an acid strength of 4.0-7.0pH on the surface is capable of readily producing effects as the separating agent. IRC84, IRC718, etc., are used as the cation exchange resin and hydroxyapatite [Ca(OH)2.3Ca3(PO4)2], etc., are used as the calcium phosphate. Silica-alumina, alumina, etc., are used as the solid acid. The respective antigens are separated by bringing the separating agent into contact with blood plasma for <=120min. Thereby the aimed HBeAg can be rapidly adsorbed. The separation is preferably carried out normally for 1-60min, more preferably 1-30min.
Organizational intervention research can be all breakthrough with no follow-through. Few effective interventions developed by scientists are widely adopted in practice. To address this research-to-practice gap and address a socially important problem, the investigators will translate their established and disseminated COMPASS (COMmunity of Practice And Safety Support) intervention to address the needs of home care workers (HCWs) with chronic pain. The burden of injuries and pain is great among HCWs, which places them at-risk for emotional distress, opioid use/misuse, and work-related disability. Moreover, HCWs are predominantly low income, middle aged women. Between 1999 and 2015 middle-aged women experienced a 471% increase in prescription opioid-related overdoses. COMPASS is a peer-led and scripted group curriculum that produced many significant impacts on meaningful outcomes for HCWs in a randomized controlled trial (Cohen's d range = .45 to .84), including increased safety communication with clients and hazard correction in homes. COMPASS was subsequently adopted by the Oregon Home Care Commission, and is currently offered statewide as a paid training course to publicly funded HCWs. While these are exceptional research-to-practice impacts, the original curriculum did not directly address chronic pain, and resulted in only small non-significant reductions in pain severity. The investigators also found that HCWs with pain-related limitations at baseline made significant safety changes, but experienced less benefit from the intervention than workers without limitations. An added barrier is that protective low-tech ergonomic tools (e.g., slide boards, transfer belts) are typically not funded by insurance. The investigators' qualitative research revealed that low-wage HCWs are often forced to improvise or do without such tools. In the translation plan, existing COMPASS lessons will be adapted for HCWs with chronic pain, and new lessons from the Pain Survival Guide (co-authored by Dr. Turk, Co-I) will integrate pain education and proven cognitive-behavioral therapy pain self-management strategies. The investigators will also strengthen injury protections by including an online ergonomic assessment and voucher for HCWs to purchase tools. The translated COMPASS for Navigating Pain (COMPASS-NP) intervention will be evaluated with a cluster randomized waitlist control design. The primary hypothesis is that COMPASS-NP will reduce pain interference with work and life. Secondary outcomes include pain/injury prevention behaviors (e.g., ergonomic tool use), injuries, pain severity, risk for opioid misuse, and worker well-being. Regional implementation and evaluation with partners in Oregon (government), Washington (labor), and Idaho (private sector) will maximize dissemination knowledge and impact. The 5-year project will accomplish 4 aims: 1) Adapt and pilot COMPASS-NP in Oregon; 2) Determine effects of COMPASS-NP across Oregon, Washington, and Idaho; 3) Describe the translation and implementation of COMPASS-NP across partners and systems; and 4) Disseminate COMPASS-NP knowledge, tools, and toolkits.