anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
INTRODUCTION: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression.
METHODS: Gene expression of TLR1-10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry.
RESULTS: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model.
CONCLUSIONS: The expression of TLR1-10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC.
The present invention belongs to pharmaceutical field, which relates to the application of the sodium tanshinone IIA sulfonate as a protective agent for the blood brain barrier in mental diseases. The present invention provides the new function of the sodium tanshinone IIA sulfonate as a protective agent for the blood brain barrier in mental disease prevention and treatment. The in vitro and in vivo studies display that the sodium tanshinone IIA sulfonate possesses definite protection function for the blood brain barrier. The present invention also possesses definite prevention and treatment function for metal disease related to the blood brain barrier injury, which comprises ischemic cerebral apoplexy. The present invention skillfully takes the blood brain barrier as the therapy target for mental diseases, which breaks through the restriction that the treatment medicine should reach the effective drug therapy concentration in accordance with the pharmacokinetic characteristics. Medicine provided in the present invention can protect the brain when the drug reaches effective intravascular concentration. Therefore better choice for treatment of the mental disease is provided.
Preterm neonates and infants who have reached Post-Menstrual Age (PMA) of at least 28 weeks and have a confirmed complicated influenza infection will be included. Participants will receive daily IV infusion of zanamivir for up to 5 days. This initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms, participant characteristics or virological tests warrant further treatment. The initial dose of IV zanamivir will be determined by PMA/corrected age and body weight. The maintenance dose and interval between the initial dose and subsequent twice-daily maintenance dose will be further determined by Principal Investigator based on renal function.
AIMS: Hepatic fibrosis is a dynamic process characterized by the net accumulation of an extracellular matrix resulting from chronic liver injury such as nonalcoholic steatohepatitis. Activation of hepatic stellate cells (HSCs) plays a role in transdifferentiation of quiescent cells into fibrogenic myofibroblasts. We aimed to examine the function of retinoic acid receptor-related orphan receptor alpha (RORα) and its novel agonistic ligand, 1-(4-benzyloxybenzyl)-3-(2-dimethylaminoethyl)-thiourea (ODH-08) against activation of HSCs using hepatic fibrosis mouse models.
MAIN METHODS: Chemical synthesis, a reporter gene assay, surface plasmon resonance analysis, and a docking study were performed to evaluate ODH-08 as a ligand of RORα. In vivo experiments with mice fed a Western diet were performed to evaluate the effect of ODH-08. The human HSC line, Lx-2, and primary mouse HSCs were employed to identify the molecular mechanisms underlying the antifibrogenic effect of ODH-08.
KEY FINDINGS: A novel RORα-selective ligand, ODH-08, was developed based on modification of JC1-40, an analog of N-methylthiourea. Administration of ODH-08 to the Western diet-fed mice reduced hepatic collagen deposition and expression levels of fibrogenic markers such as α-smooth muscle actin and collagen type I alpha 1 chain. Activation of RORα-either by transient overexpression of RORα or treatment with ODH-08-suppressed the expression of fibrogenic proteins in HSCs. The activation of RORα suppressed the activity of SMAD2 and 3, which are the primary downstream proteins of transforming growth factor β.
SIGNIFICANCE: RORα and its agonist ODH-08 have a potent antifibrotic effect, which could provide a novel antifibrotic strategy against hepatic fibrosis.
Randomized controlled single center trial. Setting: Outpatient pediatric gastroenterology (PG) clinic, Children's Hospital, London, Canada. Methodology: After a 4 week run in period, 60 children aged 5-18 years, meeting Rome 3 inclusion criteria for abdominal pain associated FGID will be recruited to the trial. After informed consent, the participants will be randomized to either a standard treatment or lifestyle modification (dietary elimination) group in the ratio of 1:1. IgG testing to food antigens will be completed in both groups using a commercially available specific IgG ELISA-based multiple food allergen panel but will ONLY be disclosed for the lifestyle modification group. The patient will receive specific advice by a dietitian to exclude a maximum of two food items from his/her diet for 4 weeks. Children will be followed-up in PG clinic at 4-weekly intervals for 16 weeks. At every clinic visit, Diary of food intake, Abdominal Pain Index (API) and Quality of Life (QOL) questionnaire will be completed by both child and parent. The standard therapy group will receive conventional treatment for Abdominal Pain (AP) as per usual practice at the PG Clinic. Response is defined as more than 50% improvement in frequency and severity of abdominal pain. At each follow up visit, non-responders will cross over to the other arm of the study. At the end of the trial, non-responders in either group will continue to receive conventional treatment in the PG Clinic. Responders will be discharged back to their family physicians. Data will be analyzed using IBM SPSS Statistics, version 22.0.
Low molecular weight cellulose derivatives are made by partial depolymerization, which comprises treating, at a temperature below 80 DEG  C. a cellulose derivative in powder form with a solution of a hydrogen halide in an anhydrous C1 to C6 aliphatic monohydric alcohol, the proportion of hydrogen halide being less than 5% by weight of the cellulose derivative being treated, and subsequently removing the hydrogen halide at least partly in vapour form. The cellulose derivative is preferably an alkyl cellulose, such as methyl or ethyl cellulose, an hydroxyalkyl cellulose, a cellulose ester such as cellulose acetate, or a carboxyalkyl cellulose. The proportion of hydrogen halide is preferably less than 2% of the weight of the cellulose derivative to be treated.  The treating temperature is preferably 30 DEG  to 60 DEG  C.  The water content of the cellulose derivative and the halide should be kept as low as possible, preferably below 5% of the sum of the weights of the starting materials and the alcohol.  The final step in the treatment may be the neutralization of the treated material with a weak base such as sodium bicarbonate.  The duration of the treatment may be about 3 hours.  The treatment is particularly adapted for treating water-soluble cellulose ethers and thereby rendering them suitable for the preparation of aqueous solutions of relatively low viscosity, e.g. below 10 cp. at 20 DEG  C. for 2% aqueous solutions.
SARS-CoV-2 infections manifest with a broad spectrum of presentations, ranging from asymptomatic infections to severe pneumonia and fatal outcomes. This review centers on asymptomatic infections, a widely reported phenomenon that has substantially contributed to the rapid spread of the pandemic. In such asymptomatic infections, we focus on the role of innate, humoral, and cellular immunity. Notably, asymptomatic infections are characterized by an early and robust innate immune response, particularly a swift type 1 IFN reaction, alongside a rapid and broad induction of SARS-CoV-2-specific T cells. Often, antibody levels tend to be lower or undetectable after asymptomatic infections, suggesting that the rapid control of viral replication by innate and cellular responses might impede the full triggering of humoral immunity. Even if antibody levels are present in the early convalescent phase, they wane rapidly below serological detection limits, particularly following asymptomatic infection. Consequently, prevalence studies reliant solely on serological assays likely underestimate the extent of community exposure to the virus.
Methods of generating and expanding human hemangio-colony forming cells and non-engrafting hemangio cells in vitro and methods of expanding and using such cells are disclosed. The methods permit the production of large numbers of hemangio-colony forming cells, non-engrafting hemangio cells as well as derivative cells, such as hematopoietic and endothelial cells. The cells obtained by the methods disclosed may be used for a variety of research, clinical, and therapeutic applications. Human non-engrafting hemangio cells are a novel progenitor cell population that is related to but distinct from the hemangioblast and human hemangio-colony forming cells. The invention also provides compositions, preparations, and solutions comprising hemangio-colony forming cells, non-engrafting hemangio cells or cells differentiated therefrom. The compositions, preparations, and solutions include cryopreserved preparations and substantially purified preparations, as well as mixed compositions formulated in combination with related hemangioblast progenitor cell types that can engraft into the bone marrow.
The program comprises a hospital group exercise program, twice a week, on alternate days, for 1h30 to 2h, each session, which included: monitoring of vital signs, peripheral oxygen saturation (SpO2), subjective perception of exertion (RPE), dyspnea and body mass; warm-up phase (10min), with ventilatory control and low-intensity upper and lower limb exercises; continuous aerobic training phase, performed on a treadmill, static cycle ergometer and/or arm ergometer (30-45min), at 60-80% of the maximum Cardiopulmonary Exercise Test load; strength training phase, with free weights, machines (10-20min), at 50-80% of the Maximum Repetition (RM), (8-12 repetitions), 1-2 sets, 8-10 exercises ( upper limbs, trunk and lower limbs); cooling phase (5-10min), with 5 to 8 relaxation, stretching and ventilatory control exercises. The progression of training loads is carried out according to RPE and dyspnea, safeguarding SpO2 values above 88-90% and Heart Rate below the maximum defined for training.
Carcinogenicity studies in animals have not been performed with tisotumab vedotin-tftv or MMAE.

MMAE was positive for genotoxicity in the in vivo rat bone marrow micronucleus study through an aneugenic mechanism. MMAE was not mutagenic in the bacterial reverse mutation (Ames) assay or the L5178 TK+/- mouse lymphoma forward mutation assay.

Fertility studies with tisotumab vedotin-tftv or MMAE have not been conducted. However, results of a repeat-dose toxicity study in monkeys indicate the potential for tisotumab vedotin-tftv to impair male reproductive function and fertility.

In a repeat-dose toxicology study conducted in monkeys for 13 weeks, doses ≥1 mg/kg tisotumab vedotin-tftv (≥0.6 times the human exposure [AUC] at the recommended dose) resulted in decreased testicular size and seminiferous tubule atrophy, reduction or absence in sperm count, and decreased sperm motility. Findings of sperm absence and decreased motility did not reverse by the end of the recovery period at doses ≥3 mg/kg (≥1.7 times the human exposure [AUC] at the recommended dose).

MMAE-containing ADCs have been associated with adverse ovarian effects when administered to sexually immature animals. Adverse effects included decrease in, or absence of, secondary and tertiary ovarian follicles after weekly administration to cynomolgus monkeys in studies of 4-week duration. These effects showed a trend towards recovery 6 weeks after the end of dosing; no changes were observed in primordial follicles.
An electrical connector comprises a dielectric housing and a plurality of contacts assembled on the dielectric housing. The dielectric housing comprises a receptacle portion and a fixing portion. The contact comprises a contact portion, an extending portion, a retention portion and a soldering portion. The retention portion is fixed in the fixing portion. The contact portion extends into the receptacle portion and part of which is exposure. The extending portion is electrically connected with the retention portion and the soldering portion, and comprises two pairs of locking portions extending outwardly. The dielectric housing comprises a fastness portion corresponding to the locking portion and the fastness portion defines a fastness recess. The fastness recess comprises a fastness surface with a fastness block and a leading surface with a ladder shape corresponding to the fastness surface. The fastness recess matched with the locking portion to restrict the movement of the contacts.
AIM: To investigate the possible covariation of grey matter volume (GMV) and white matter fractional anisotropy in infants with spastic cerebral palsy (CP) and periventricular white matter injury.
METHOD: Thirty-nine infants with spastic CP and 25 typically developing controls underwent structural magnetic resonance imaging and diffusion tensor imaging. Multimodal canonical correlation analysis with joint independent component analysis were used to capture differences in GMV and fractional anisotropy between groups. Correlation analysis was performed between imaging findings and clinical features.
RESULTS: Infants with spastic CP showed one joint group-discriminating component (i.e. GMV-fractional anisotropy) associated with regions in the cortico-basal ganglia-thalamo-cortical loop and in the corpus callosum compared to typically developing controls and one modality-specific group-discriminating component (i.e. GMV). Significant negative correlations were found between loadings in certain regions and the motor function score in spastic CP.
INTERPRETATION: In infants with spastic CP, covarying GMV-fractional anisotropy and altered GMV in specific regions were implicated in motor dysfunction, which confirmed that simultaneous GMV and fractional anisotropy changes underly motor deficits, but might also extend to sensory, cognitive, or visual dysfunction. These findings also suggest that multimodal fusion analysis allows for a more comprehensive understanding of the relevance between grey and white matter structures and its crucial role in the neuropathological mechanisms of spastic CP.
PROBLEM TO BE SOLVED: To obtain the subject medicine capable of improving the syndromes of a hepatic disease patient, especially hyperammonemia, and little in side effects by including highly pure raffinose as an active ingredient. SOLUTION: This hepatic disease medicine contains highly pure raffinose as an active ingredient. The raffinose is preferably administered at a daily dose of 0.3-0.9g per kg of a body. The raffinose is produced e.g. from beet roots by a known method. The medicine may further contain a known vehicle, a known shape-retaining agent, a known filler, etc.
Lateral epicondylitis is one of the elbow conditions that affects about 1-3% of the population at large. It produces a heavy burden of workdays lost and residual impairments. Although many treatment modalities are used, few of them rest on scientific evidence and none has been proven more effective than the others. This lack of evidence on treatments for lateral epicondylitis may stem from several sources, including the possible self-limiting nature of the condition, the lack of pathophysiological data, the methodological shortcomings of available studies, and the existence of numerous factors influencing the outcome. The physiotherapeutic treatment has been shown to be effective. In general, it must include manual therapy to relieve the pain and improve the joint's range of motion (ROM), taking into account that it must be performed under the pain threshold. Mulligan mobilization with movement (MWM) is a modern technique developed by Mulligan for treating lateral epicondylitis (LE). Instrument-assisted soft tissue mobilization is a form of augmented soft tissue mobilization (IASTM) in which stainless steel instruments are utilized to apply controlled microtrauma to the affected soft tissues. sixty patients will be allocated randomly to three groups; the first one will receive mulligan mobilization with movement, the second one will receive instrument-assisted soft tissue mobilization and the third one will receive traditional therapy three times a week for four weeks
The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain. In tumor microenvironment inactive fibroblasts are converted into an active form that is cancer-associated fibroblasts (CAFs). Neurotrophins they also increase the level of Substance P, calcitonin gene-related peptide which is also involved in pain. Matrix metalloproteases are the zinc-associated proteases enzymes which activates proinflammatory interleukin-1β into its activated form and are responsible for release and activation of Substance P which is responsible for neuropathic pain by transmitting pain signal via dorsal root ganglion. All the molecules and their role in being responsible for neuropathic pain are described below.
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome with highly variable clinical manifestations and that has a worldwide incidence of approximately 1/2500. The most common lesion is the cutaneous neurofibroma, appearing on the skin of 90% of adults with NF1. The number of cutaneous neurofibromas in an affected individual can vary from a few to several thousand. These lesions may be surgically removed, but typically recur, and surgical removal often leads to scarring. Intralesional administration of diclofenac was previously reported with favorable results, and significant inflammatory processes were observed within the treated neurofibromas, with tissue necrosis and detachment of some treated neurofibromas, effects that were not observed among the control neurofibromas. The primary objective of this study is to evaluate the use of topical diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. The secondary objective of this study is to assess the safety of the use of topical diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 \& 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period. Prior to any study-related procedure, written informed consent will be obtained from the participant. The Clinical Research From will be filled, stored, coded, and the data will be analyzed using GraphPad Prism, v. 5.0. Frequency tables will be generated and central tendencies calculated (mean, median, mode).
BACKGROUND: Recently, elevated levels of plasma erythritol have been associated with major adverse cardiovascular events (MACE). It is known that people with HIV (PWH) have a higher cardiovascular disease burden. Whether PWH have higher levels of plasma erythritol has not been evaluated. This study aimed to assess if blood erythritol levels are elevated in PWH and to examine relationships between erythritol and dietary, cardiometabolic, inflammatory, and gut health markers.
METHODS: Plasma erythritol levels were measured using frozen samples from 162 participants, including 109 PWH and 53 people without HIV (PWoH) in a parent study. General linear models were used to assess the linear relationship between characteristics, cardiovascular measures, markers of body composition, inflammation, and gut integrity with plasma erythritol. Logistic regression was used to assess risk factors associated with PWH, and cumulative logit models were used to investigate which factors were associated with having the highest plasma erythritol levels among PWH.
RESULTS: Compared to PWoH, PWH had higher plasma erythritol levels (p = 0.03). Every 10% increase in VLDL (p = 0.01), visceral adipose tissue (p < 0.0001), or TNFrI (p = 0.01) was associated with an approximately 1% increase in plasma erythritol. Among PWH, HgbA1c (p = 0.003), TNFrI (p = 0.002), and IFAB-P (p = 0.004) were associated with having the highest tertile of plasma erythritol (≥3.6 μM). Compared to PWoH, PWH were more than two times as likely (p = 0.03) to have plasma erythritol ≥ 3.6 μM.
CONCLUSIONS: We identified positive associations between plasma erythritol levels and several factors, including HIV status, BMI, adipose tissue, TNFr1, HbA1c, and VLDL. These results underscore the importance of further investigating the role of elevated plasma erythritol levels in people with HIV, particularly in light of their increased vulnerability to cardiovascular and metabolic diseases.