anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PURPOSE OF REVIEW: The purpose of this review is to highlight recent genetic studies of the Amish and Mennonite (Plain) communities. For decades, the study of genetically isolated populations has improved our understanding and management of genetic diseases that affect all populations.
RECENT FINDINGS: Major themes of current genetic research of the Amish and Mennonites include new causative gene and new candidate gene discovery, phenotype expansion of previously identified genetic disease, and a target for AAV9-mediated gene therapy. Additionally, several genome-wide association studies (GWAS) examining complex traits such as dementia, cardiometabolic disease, and age-related macular degeneration have been conducted. Finally, clinically relevant studies of attitudes of the Plain community towards genetic testing and telemedicine, as well as reviews of and management suggestions for the Amish variants of propionic acidemia and APOB -associated familial hypercholesterolemia have been recently published.
SUMMARY: Recent genetic studies of the Plain community continue to highlight the value of studying isolated populations to propel genetic disease discovery and treatment. Additionally, population-specific polygenic risk scores are needed for underrepresented and minority populations, to avoid exacerbating disparities in medical genetics care. Finally, it is important for clinicians to develop management guidelines for variants common in this rapidly growing population, such as propionic acidemia.
This study consists of a single-arm clinical study among 30 older adults taking benzodiazepine receptor antagonists (BRZA) to assess the feasibility of protocol-driven BRZA deprescribing augmented with combined acupuncture and yoga. Adults 65 years or older that are taking BRZA will be recruited. Deprescribing will be provided at weekly visits with a psychiatric nurse practitioner at the Osher Center for Integrative Health at Vanderbilt University Medical Center. Participants will receive acupuncture and yoga from a staff acupuncturist and yoga instruction from a yoga instructor at the Osher Center. Feasibility of study enrollment will occur through the study enrollment period. Feasibility of study treatments will be evaluated during and after study treatment delivery. Feasibility of study outcome assessments will occur at baseline, 4, 8, and 12 weeks. Throughout the research process, investigators will engage a Stakeholder Advisory Panel consisting of patients and clinicians.
Patients receive pacritinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue to receive BTK inhibitor per standard of care. Additionally, patients undergo blood sample collection, optional tissue biopsy, bone marrow biopsy and aspiration and PET/CT throughout the study.
Parkinsons disease is a neurodegenerative disease in which dopamine neurons are gradually lost in the substantia nigra of a brain. The inventors have clarified that a PIM2 fusion protein can protect dopamine neurons from oxidation stress in an SH-SY5Y neuroblastoma cell and Parkinsons disease animal model. It has been confirmed that the PIM2 fusion protein is smoothly moved into SH-SY5Y cells and into the substantia nigra of a brain through a Western blot analysis. The PIM2 fusion protein remarkably inhibits the generation of active oxygen species induced by MPP^+ and the fragmentation of DNA, and eventually induces the survival of SH-SY5Y cells. In addition, immunohistochemical analysis data using TH antibodies and cresyl violet coloration shows that the PIM2 fusion protein remarkably protects dopamine cells in the substantia nigra with respect to oxidation stress like MPTP. Accordingly, the PIM2 fusion protein can be used in preventing and treating Parkinsons disease.
Participants will receive 30 minutes of sham electroacupuncture before anaesthesia induction.The sham group will use non-acupuncture points: 20 mm above GV24 and 20 mm lateral to GB13. These points, in different dermatomes from true acupoints, minimise location-specific effects. The procedure will match the active group, excluding needle manipulation, de qi sensation and electrical output.
Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia-reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases.
All enrolled patients need to undergo 5.0TbpMRI and 3.0TbpMRI (within one month). The magnetic resonance imaging sequences mainly include T1WI, multi-plane T2WI and multi-b-value DWI images.
BACKGROUND/AIM: Atherosclerosis is a vascular inflammatory disease characterized by the activation and stress of various inflammatory cells, leading to the development of coronary artery disease and subsequently acute myocardial infarction (AMI). Among AMI cases, ST-segment elevation myocardial infarction (STEMI) is typically more severe than non-STEMI (NSTEMI). UL16-binding proteins (ULBPs), which are NKG2D ligands, can be expressed on the surface of stressed and activated cells, prompting these cells to generate microparticles (MPs). Consequently, MPs carrying ULBPs, particularly ULBP1 (ULBP1+ MPs), may be released into the bloodstream. This study aimed to investigate the association between ULBP1+ MPs and the presence of AMI and its severity.
MATERIALS AND METHODS: We recruited 58 AMI patients and 45 age-matched control subjects. Levels of ULBP1+ MPs and ULBP1+ MPs originating from T lymphocytes (ULBP1+ TMPs) were measured using flow cytometry.
RESULTS: Both ULBP1+ MP and ULBP1+ TMP levels were significantly elevated in AMI patients compared to controls. Elevated levels of these MPs were independent risk factors for AMI with odds ratios (OR) of 4.3 (95%CI=1.5-12.3) for ULBP1+ MPs and 5.8 (95%CI=2.0-17.0) for ULBP1+ TMPs. Additionally, ULBP1+ TMP levels were significantly higher in STEMI patients compared to NSTEMI patients, with an independent association observed between ULBP1+ TMPs and STEMI (OR=3.9; 95%CI=1.2-12.8).
CONCLUSION: Elevated levels of ULBP1+ MPs and ULBP1+ TMPs are associated with AMI and its severity. These biomarkers could serve as indicators of vulnerable plaques that lead to AMI.
The GnRH-a (Diphereline® or Decapetyl®) 0.1mg will be administered for about 14 to 20 days for down-regulation. Gonal-f® will be administrated as routinely practiced by investigators. GnRH-a types, GnRH-a and FSH doses will be adjusted according to the clinical experiences of investigators in each site.
Part 1 of the study will determine the safety of continuous twice a day oral dosing of GRN-300, with each cycle consisting of 28 days of treatment. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of side effects and DLTs. The maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of GRN-300 as a single agent will be determined. The overall duration of Part 1 will be approximately 24-36 months, depending on the rate of enrollment and the number of subjects enrolled.
1. A medicament comprising a material carrier provided with information of an active medical substance, characterized in that said material carrier is an active medical substance in a therapeutic dose onto which is transferred, using bioenergetic exchange, information from a potentiated medicament prepared according to homeopathic methods and having the same basic chemical formula or composition as the active medicinal substance. 2. A medicament comprising a material carrier provided with information of an active medical substance, characterized in that comprises said active medical substance in a therapeutic dose as a material carrier to which is added a potentiated medicament prepared according to homeopathic methods and having the same basic chemical formula or composition. 3. A medicament as claimed in claim 2, characterized in that the active medical substance and added to it a potentiated medicament have the same (identical) medicinal form. 4. A method of treating an organism by simultaneous administration of a medicament in a therapeutic dose and potentiated medicament prepared according to homeopathic methods and having the same basic chemical formula or composition.
A method of operating a distributed processing, interactive computer network is described. The network is designed to provide very large numbers of simultaneous users access to large numbers of applications which feature interactive text/graphic sessions. The network includes one or more servers, interactive applications, and one or more reception systems, the reception systems being capable of communicating with the respective servers and receiving applications from them. In this arrangement, application are structured from packets termed “objects”, the objects including the display data and/or program code required to support execution of the application. When a request for an application is received at a reception system, if any objects for the application are unavailable from the reception system, the objects are requested from the server and supplied to the reception systems requesting the application objects. In accordance with the method, the respective reception systems include display interfaces for presenting applications to respective users the respective display interfaces featuring a plurality of display partitions. Also in accordance with the method, at least some of the respective applications are divided into sections, the respective sections being designed to form at least a part of an application display page. Further, application sections are constructed from objects such that display page parts of one or more respective applications may be controllably presented at the partitions of the interface to permit at least application page part nesting, scrolling and navigation, the objects being of multiple types and including display data and/or program code for enabling execution of applications and their presentation at the interface partitions of the respective user reception systems.
Neuropathic pain (NP) is usually treated with analgesics and symptomatic therapy with poor efficacy and numerous side effects, highlighting the urgent need for effective treatment strategies. Recent studies have reported an important role for peroxisome proliferator-activated receptor alpha (PPARα) in regulating metabolism as well as inflammatory responses. Through pain behavioral assessment, we found that activation of PPARα prevented chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia. In addition, PPARα ameliorated inflammatory cell infiltration at the injury site and decreased microglial activation, NOD-like receptor protein 3 (NLRP3) inflammasome production, and spinal dendritic spine density, as well as improved serum and spinal cord metabolic levels in mice. Administration of PPARα antagonists eliminates the analgesic effect of PPARα agonists. PPARα relieves NP by inhibiting neuroinflammation and functional synaptic plasticity as well as modulating metabolic mechanisms, suggesting that PPARα may be a potential molecular target for NP alleviation. However, the effects of PPARα on neuroinflammation and synaptic plasticity should be further explored.
Periprosthetic joint infections (PJIs) are serious complications of prosthetic surgery. The criteria for the diagnosis of PJI integrate clinical and laboratory findings in a complex and sometimes inconclusive workflow. Host immune factors hold potential as diagnostic biomarkers in bone and joint infections. We reported that the humoral pattern-recognition molecule long pentraxin 3 (PTX3) predicts PJI in total hip and knee arthroplasty (THA and TKA, respectively). If and how genetic variation in PTX3 and inflammatory genes that affect its expression (IL-1β, IL-6, IL-10, and IL-17A) contributes to the risk of PJI is unknown. We conducted a case-control study on a Caucasian historic cohort of THA and TKA patients who had prosthesis explant due to PJI (cases) or aseptic complications (controls). Saliva was collected from 93 subjects and used to extract DNA and genotype PTX3, IL-1β, IL-6, IL-10, and IL-17A single-nucleotide polymorphisms (SNPs). Moreover, the concentration of IL-1β, IL-10, and IL-6 was measured in synovial fluid and plasma. No association was found between PTX3 polymorphisms and PJI; however, the AGG haplotype, encompassing rs2853550, rs1143634, and rs1143627 in IL-1β, was linked to the infection (p = 0.017). Also, synovial levels of all inflammatory markers were higher in cases than in controls, and a correlation emerged between synovial concentration of PTX3 and that of IL-1β in cases only (Spearman r = 0.67, p = 0.004). We identified a relationship between rs2853550 and the synovial concentration of IL-1β and PTX3. Our findings suggest that IL-1β SNPs could be used for the early identification of THA and TKA patients with a high risk of infection.
The invention discloses a nutritional product for clearing and protecting the lungs and a preparation method thereof. The nutritional product includes the following raw materials 5 in parts by weight: 45-55 parts of aster, 40-50 parts of loquat leaves, and 30-45 parts of Fritillaria fritillary. ‚ 25-35 parts of Ophiopogon japonicus, 20-30 parts of Polygonatum odoratum, 15-30 parts of coix seed, 15-30 parts of Tremella fuciforrnis, 15-24 parts of Polygala, 10-16 parts of Platycodon, 10-16 parts of Luo Han Guo, 5-5 parts of White Poria. 15 parts, lily 3-12 parts, licorice 5-10 parts, sweet almond 3-10 parts, ginkgo l- 10 10 parts, honey 1-5 parts, ginseng 0.5-3 parts, Cordyceps militaris 0.5-5 parts. The raw materials of the nutritional product have a synergistic effect. Comprehensive conditioning from multiple points such as the lungs, liver, heart, kidney, spleen, stomach, etc. can enhance the effects of nourishing yin and moistening the lungs, clearing away heat and detoxification, eliminating phlegm and relieving cough. , can 15 improve the therapeutic effect, at the same time, after patients use this nutritional product, systemic symptoms such as cough, phlegm, itchy throat and chest tightness have basically disappeared. The total treatment effectiveness is as high as 95%, which can significantly improve patients' symptoms and improve their quality of life.
Valsartan and hydrochlorothiazide tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

Thiazides cross the placenta, and use of thiazides during pregnancy is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

When pregnancy is detected, discontinue valsartan and hydrochlorothiazide tablets as soon as possible [see Use in Specific Populations (8.1)] .
Deletion of Runx2 gene in proliferating chondrocytes results in complete failure of endochondral ossification and perinatal lethality. We reported recently that mice with Runx2 deletion specifically in hypertrophic chondrocytes (HCs) using the Col10a1-Cre transgene survive and exhibit enlarged growth plates due to decreased HC apoptosis and cartilage resorption. Bulk of chondrogenesis occurs postnatally, however, the role of Runx2 in HCs during postnatal chondrogenesis is unknown. Despite limb dwarfism, adult homozygous (Runx2HC/HC) mice showed a significant increase in length of growth plate and articular cartilage. Consistent with doubling of the hypertrophic zone, collagen type X expression was increased in Runx2HC/HC mice. In sharp contrast, expression of metalloproteinases and aggrecanases were markedly decreased. Impaired cartilage degradation was evident by the retention of significant amount of safranin-O positive cartilage. Histomorphometry and μCT uncovered increased trabecular bone mass with a significant increase in BV/TV ratio, trabecular number, thickness, and a decrease in trabecular space in Runx2HC/HC mice. To identify if this is due to increased bone synthesis, expression of osteoblast differentiation markers was evaluated and found to be comparable amongst littermates. Histomorphometry confirmed similar number of osteoblasts in the littermates. Furthermore, dynamic bone synthesis showed no differences in mineral apposition or bone formation rates. Surprisingly, three-point-bending test revealed Runx2HC/HC bones to be structurally less strong. Interestingly, both the number and surface of osteoclasts were markedly reduced in Runx2HC/HC littermates. Rankl and IL-17a ligands that promote osteoclast differentiation were markedly reduced in Runx2HC/HC mice. Bone marrow cultures were performed to independently establish Runx2 and hypertrophic chondrocytes role in osteoclast development. The culture from the Runx2HC/HC mice formed significantly fewer and smaller osteoclasts. The expression of mature osteoclast markers, Ctsk and Mmp9, were significantly reduced in the cultures from Runx2HC/HC mice. Thus, Runx2 functions extend beyond embryonic development and chondrocyte hypertrophy by regulating cartilage degradation, osteoclast differentiation, and bone resorption during postnatal endochondral ossification.
The six volunteers from Groups 1, 2 and 3 in will undergo secondary challenge using the optimal inoculum, as determined in Phase A of the study. They will constitute 'Group 4' in Phase B. This will occur approximately eight months (and up to nine months) later after their primary challenge.
PURPOSE:To obtain an inexpensive mass-producible composition, useful for reducing uremic substances and capable of suppressing the progress of chronic renal insufficiency, avoiding dialytic introduction and suppressing deterioration of the chronic renal insufficiency without any problems even in continuous use for a long period. CONSTITUTION:A composition for reducing uremia substances containing (-)- epiqallocatechin theta3-O-Rallate (EGCg) as an active ingredient. Thereby, the aforementioned composition, useful for reducing the uremic substances and capable of reducing the amount of methylguanidine which is a uremic substance, effective in improving symptoms of chronic renal insufficiency caused by the uremic substances and having a high safety is obtained. The above-mentioned active ingredient is prepared by using operation such as extraction or purification from green tea; however, the active ingredient derived from other raw materials or chemically synthesized substances may be used. If green tea leaves are used as the raw material, the tea leaves in any stages of raw leaves to finished green tea (dried green tea) may be used. Furthermore, any of unfermented tea, semifermented tea or fermented tea can be used. In addition, the chronic renal insufficiency is irreversible diseases and relies on therapeutic methods such as alimentary therapy, hemodialysis or renal transplanting.
BACKGROUND: Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic-lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH.
METHODS: A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro.
RESULTS: Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1β at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines.
CONCLUSION: PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients.
The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The said formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.