anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The new structure of the interaction of IgG with an antigen and a complement is proposed. According to this structure, the signal passes into the Fc fragment by a switch of the hinge region with its bend ''in two'' and the interaction of the changed hydrophobic patches of the Fab fragments with the Fc fragment. The changed conformation of the Fc fragment, especially in the pFc' region, became similar in shape to a scorpion's tail which could presumably interact by its hydrophobic patches in the outside face of the CH3 domain with the complement component C1 to activate the complement. The analysis of data from old literature gives strong evidence for this ''scorpion'' structure. It is proposed that the small protein (m.w. SIMILAR 2000) associated with IgG (Dudich, E.I. and Dudich, I. Dokl. Acad. Sci. USSR 260,1259, 1981) serves as the IgG protector against a strong interaction with the complement. The dissociation of this small protein, after a large distorsion during the precipitation reaction with an antigen, allows for a strong fixation of the globular heads of the C1q subcomponent. The proposed structure explains: the role of an affinity in the aggregation and in the complement activation; and consequently, the mechanisms of a great number of associated diseases. This ''scorpion'' structure explains the interaction between B and T-lymphocytes which is exemplified by both types of experimental results, that is, by direct interaction as well as by interaction with soluble substances. The examples with extremely important practical consequences are proposed.
The present invention relates to new DNA sequences, to new proteins coded for by such DNA sequences, and to the use as further described below of such proteins. The invention also encompasses vectors, such as plasmid constructs, comprising such DNA sequences, being capable of expressing the desired enzyme. The invention also includes host organisms transfected with such constructs e.g. bacteria yeast, mammalian cells, and transgenic animals.  The invention also includes processes for the preparation of the novel products of the invention. The new proteins of the invention are related to an enzyme, known i.a. as human bile salt-stimulated lipase.
Neuropathic pain (NP) affects approximately 6.9-10% of the world's population and necessitates the development of novel treatments. Mitochondria are essential in the regulation of cell death. Neuroimmune mechanisms are implicated in various forms of cell death associated with NP. However, the specific involvement of mitochondrial dysfunction and disulfidptosis in NP remains uncertain. Further research is required to gain a better understanding of their combined contribution. Our comprehensive study employs a variety of bioinformatic analysis methods, including differential gene analysis, weighted gene co-expression network analysis, machine learning, functional enrichment analysis, immune infiltration, sub-cluster analysis, single-cell dimensionality reduction and cell-cell communication to gain insight into the molecular mechanisms behind these processes. Our study rationally defines a list of key gene sets for mitochondrial dysfunction and disulfidptosis. 6 hub mitochondrial genes and 3 disulfidptosis-related genes (DRGs) were found to be associated with NP. The key genes were predominantly expressed in neurons and were lowly expressed in the NP group compared to SHAM. In addition, our macrophages used the APP (Amyloid precursor protein)-CD74 (MHC class II invariant chain) pathway to interact with neurons. These results suggest that NP is interconnected with the mechanistic processes of mitochondrial dysfunction and disulfidptosis, which may contribute to clinically targeted therapies.
The extracellular matrix (ECM) is present in all tissues and crucial in maintaining normal tissue homeostasis and function. Defects in ECM synthesis and remodeling can lead to various diseases, while overproduction of ECM components can cause severe conditions like organ fibrosis and influence cancer progression and therapy resistance. Collagens are the most abundant core ECM proteins in physiological and pathological conditions and are predominantly synthesized by fibroblasts. Previous efforts to target aberrant collagen synthesis in fibroblasts by inhibiting pro-fibrotic signaling cascades have been ineffective. More recently, metabolic rewiring downstream of pro-fibrotic signaling has emerged as a critical regulator of collagen synthesis in fibroblasts. Here, we propose that targeting the metabolic pathways involved in ECM biomass generation provides a novel avenue for treating conditions characterized by excessive collagen accumulation. This review summarizes the unique metabolic challenges collagen synthesis imposes on fibroblasts and discusses how underlying metabolic networks could be exploited to create therapeutic opportunities in cancer and fibrotic disease. Finally, we provide a perspective on open questions in the field and how conceptual and technical advances will help address them to unlock novel metabolic vulnerabilities of collagen synthesis in fibroblasts and beyond.
Dietary fats influence gene expression and several metabolic pathways. Therefore, it is crucial to study the role of personal genotypes in the interaction between fat consumption and cardiometabolic markers. This research aimed to determine the interaction of the rs708272 polymorphism of CETP and the fatty acid intake with changes in the HOMA-IR in adults living with overweight or obesity. The current study was a secondary analysis of an 8-week controlled clinical trial. The final sample for this analysis comprised 78 Mexican adults with the Cholesteryl Ester Transfer Protein (CETP) rs708272 polymorphism who followed a dietary intervention. Using an interaction analysis, we evaluated the fatty acid intake and the genotypes of rs708272, with changes in blood glucose, insulin, and the HOMA-IR from baseline to endpoint. Our findings suggest a significant interaction between the trans fatty acid intake and the GG genotype with changes in glucose (p = 0.024), insulin (p = 0.004), and the HOMA-IR (p = 0.002). The higher the consumption of trans fatty acids, the less these markers of glucose metabolism were reduced. carriers of the GG genotype may benefit from limiting dietary trans fatty acid intake, as there was no reduction in plasma glucose and insulin despite a hypocaloric dietary intervention in adults with overweight and obesity.
The main goal of this study is to determine typical values of dose area product (DAP) and difference in the effective dose (ED) for pediatric electrophysiological procedures on the heart in relation to patient body mass. This paper also shows DAP and ED in relation to the indication, the arrhythmia substrate determined during the procedure, and in relation to the reason for using radiation. Organ doses are described as well. The subjects were children who have had an electrophysiological study done with a 3D mapping system and X-rays in two healthcare institutions. Children with congenital heart defects were excluded. There were 347 children included. Significant difference was noted between mass groups, while heavier children had higher values of DAP and ED. Median DAP in different mass groups was between 4.00 (IQR 1.00-14.00) to 26.33 (IQR 8.77-140.84) cGycm2. ED median was between 23.18 (IQR 5.21-67.70) to 60.96 (IQR 20.64-394.04) µSv. The highest DAP and ED in relation to indication were noted for premature ventricular contractions and ventricular tachycardia-27.65 (IQR 12.91-75.0) cGycm2 and 100.73 (IQR 53.31-258.10) µSv, respectively. In arrhythmia substrate groups, results were similar, and the highest doses were in ventricular substrates with DAP 29.62 (IQR 13.81-76.0) cGycm2 and ED 103.15 (IQR 60.78-266.99) µSv. Pediatric electrophysiology can be done with very low doses of X-rays when using 3D mapping systems compared to X-rays-based electrophysiology, or when compared to pediatric interventional cardiology or adult electrophysiology.
PCT No. PCT/GB93/00711 Sec. 371 Date Dec. 5, 1994 Sec. 102(e) Date Dec. 5, 1994 PCT Filed Apr. 5, 1992 PCT Pub. No. WO93/20103 PCT Pub. Date Oct. 14, 1993A method of identifying peptides of an antigen of interest which are capable of recognition by or induction of cytotoxic T lymphocytes, comprises the steps of: ascertaining a "motif" of peptides which bind to a chosen HLA class I allele; providing peptides having this motif which are present in the known sequence of the antigen of interest; screening the peptides using an HLA assembly assay; and screening the resulting peptides for recognition by or induction of cytotoxic T lymphocytes. The above peptides have been identified by this method, and the peptides and vaccines containing them are also claimed.
In cervical biopsies, for diagnosis of Human Papilloma Virus (HPV) related conditions, the immunohistochemical staining for p16 has a diagnostic value only if diffusely and strongly positive, pattern named "block-like". "Weak and/or focal (w/f) p16 expression" is commonly considered nonspecific. In our previous study, we demonstrated the presence of high-risk HPV (hrHPV) DNA by LiPa method in biopsies showing w/f p16 positivity. The aim of the present study was to investigate the presence of hrHPV-DNA by CISH in the areas showing w/f p16 expression. We assessed the presence of hrHPV16, 18, 31, 33, 51 by CISH in a group of 20 cervical biopsies showing w/f p16 expression, some with increased Ki67, and in 10 cases of block-like expression, employed as control. The immunohistochemical p16 expression was also assessed by digital pathology. hrHPV-CISH nuclear positivity was encountered in 12/20 cases of w/f p16 expression (60%). Different patterns of nuclear positivity were identified, classified as punctate, diffuse and mixed, with different epithelial distributions. Our results, albeit in a limited casuistry, show the presence of HPV in an integrated status highlighted by CISH in w/f p16 positive cases. This could suggest the necessity of a careful follow-up of the patients with "weak" and/or "focal" immunohistochemical patterns of p16, mainly in cases of increased Ki67 cell proliferation index, supplemented with molecular biology examinations.
Chronic kidney disease (CKD) has become an important public health problem threatening human health worldwide. The prevalence rate of CKD in Chinese adults is 10.8%, but the awareness rate and diagnosis rate are generally low. At present, the assessment of renal impairment in CKD mainly relies on laboratory tests, such as estimated glomerular filtration rate (eGFR) and urinary protein/creatinine ratio, and the value of functional MRI in the assessment of renal impairment in patients with CKD is unclear. As a new sequence still in the scientific research stage, MR Fingerprinting can simultaneously generate quantitative T1 maps, T2 maps and proton-weighted images in one breath holding scan, with short scanning time, high repeatability and accuracy. It has been proved that quantitative techniques of T1 mapping and T2 mapping are valuable for evaluating the degree of renal fibrosis and water content. Kidney is a blood-rich organ, and the blood flow of kidney is of great significance to the evaluation of renal function. ASL uses hydrogen protons in arterial blood as an endogenous tracer to evaluate tissue blood perfusion, and can quantitatively evaluate renal blood perfusion in patients with CKD without the use of exogenous contrast agents, avoiding the risk of aggravated renal damage and nephrogenic fibrosis caused by injection of gadoline-containing contrast agents. The objective of our study was to explore the value of MRF sequence-generated quantitative maps combined with ASL renal perfusion imaging in the assessment of renal impairment in chronic kidney disease.
BACKGROUND: A positive circumferential resection margin (CRM) after rectal cancer surgery, which can be the result of direct or indirect tumour involvement, has consistently been associated with increased local recurrence and poorer survival. However, little is known of the differential impact of the mode of tumour involvement on outcomes.
METHODS: 1460 consecutive patients undergoing rectal cancer resection between 2003 and 2018 were retrospectively assessed. Histopathology reports for patients with a positive CRM were reviewed to determine cases of direct (R1-tumour) or indirect tumour involvement (R1-other). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. The role of the mode of CRM positivity was examined by univariate and multivariate Cox proportional hazards models.
RESULTS: Eighty-five patients had an R1 resection due to CRM involvement (5.8%). Of those, 69 were due to direct tumour involvement, while 16 were from indirect causes. Kaplan-Meier analysis revealed that R1-other was associated with increased OS (hazard ratio 0.40, log-rank P = 0.006) and DFS (P = 0.043). Multivariate regression confirmed that the mode of CRM positivity was an independent predictor of OS. More interestingly, the patterns of recurrence were different between the two groups, with R1-tumour leading to significantly more local recurrence (P = 0.04).
CONCLUSIONS: Our data strongly suggests that direct tumour involvement of the CRM confers worse prognosis after rectal cancer surgery. Importantly, differences in the site and frequency of recurrences make a case for better stratification of patients with a positive CRM to guide treatment decisions.
A cationic adhesive-type natamycin nanometer eye drop comprises natamycin, a proper amount of osmoregulator and pH regulator. The eye drop is characterized by further comprising chitosan, pluronic F-68 and phospholipid, wherein, the mass percent concentration of the phospholipid in the eye drop is 0.01-2%, the mass percent concentration of the pluronic F-68 in the eye drop is 0.1-20%, and the masspercent concentration of the chitosan in the eye drop is 0.01-4%. The molecular weight of the chitosan is 5000-300000, and the deacetylation degree of the chitosan is greater than 85%. The natamycinnanometer eye drop is characterized by making a common natamycin suspension into suspension particles with the diameter ranging from 10nm to 1000nm, thus increasing solubility of the eye drop and enhancing safety and effectiveness. The natamycin particles of the common suspension are modified by the phospholipid and the chitosan to cause the particles to be positively charged, which is helpful toimprove absorption of the eye drop by cornea, enhances drug effect and prolongs the action time of the eye drop. And the chitosan has bioadhesion function, which enhances the adhesiveness between medicinal particles and the cornea.
Patients eligible for the trial and having signed their consent to participate will undergo a dosimetric scan at baseline. 48 hours later (minimum), a Metformin therapy will be started at a dosage of 850 mg 2 times / day ( = 1700 mg / day). Seven days later (minimum) and up to 48 hours before surgery, the dosage of Metformin will be increased to 850 mg 3 times / day ( = 2550 mg / day). This very same day (J10), patients will start a radiochemotherapy. For 5 weeks, 5 days out of 7, patients will receive 800 mg/m² of Capecitabine 2 times / day (on morning and evening) ( = 1600 mg / m² / day) and a 3D irradiation or an Intensity-Modulated Radiation Therapy (IMRT) of a total dose of 50 Gy (5 sessions of 2 Gy per week). 6 to 8 weeks after completion of the chemoradiotherapy, surgery will be scheduled. It will consist of a tumor resection with total resection of the meso rectum.

Prior to the start of treatment, patients will have a clinical and a paraclinical examination and will undergo a laboratory examination. Once a week during the radiochemotherapy, patients will have a clinical examination and will undergo a laboratory examination. Three weeks after the end of the radiochemotherapy, patients will have a clinical examination. Before surgery, patients will have a clinical and a paraclinical examination. Finally, at the end of the study, patients will have a clinical examination.
OBJECTIVE: Postpartum hemorrhage is a leading cause of maternal mortality and morbidity around the globe. The novel low-suction vacuum hemorrhage device (VHD) provides an alternative treatment option for cases of postpartum hemorrhage when first-line uterotonic agents fail. This systematic review aims to review current data evaluating the overall efficacy and safety of VHDs in treating postpartum hemorrhage.
METHODS: We searched CINAHL Ultimate, Academic Search Premier, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE with Full Text, and PubMed and reference lists of retrieved studies for eligible studies that included outcomes of effectiveness, efficacy, or safety. Two independent reviewers used Covidence.org to screen Titles and Abstracts for 69 studies of which six were included in the analysis. Secondary outcomes measured across studies included time to bleeding control, total device deployment time, and adverse effects.
RESULTS: Six nonrandomized trials (N = 1018 participants) included studies conducted in Indonesia, the United States, Switzerland, and Canada. The VHDs were found to have 90% effectiveness in achieving bleeding control across the studies. For most patients, this was achieved in <5 min and required a total device deployment time of 3 h. Reported adverse events were not considered life-threatening, including endometritis in 11 patients and red blood cell transfusions in 38% of patients.
CONCLUSION: VHDs have the potential to be used as a rapidly effective means for mechanical intervention of postpartum hemorrhage. The efficacy and safety of VHDs must be further studied at the randomized controlled trial level to determine their clinical usage.
Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in the neuroligin 3 (NLG3) gene are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we found that the conditional knockout of Nlg3 (Nlg3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. Nlg3 CKO in the MS caused hyperactivity of MSGABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induced social memory deficits and sleep loss in C57BL/6J mice. In contrast, inactivation of these neurons ameliorated social memory deficits and sleep loss in Nlg3-CKO mice. Sleep deprivation led to social memory deficits, while social isolation caused sleep loss, both resulting in a reduction in NLG3 expression and an increase in activity of GABAergic neurons in the MS from C57BL/6J mice. Furthermore, MSGABA-innervated CA2 neurons specifically regulated social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively controlled sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MSGABA neurons impair social memory and disrupt sleep resulting from Nlg3 CKO in the MS, and achieve the modality specificity through their divergent downstream targets.
BACKGROUND: Depression post-myocardial infarction (MI) is becoming more prevalent. The gut-brain axis (GBA), influenced by the gut microbiota, is a critical component in understanding depression post-MI. Despite the well-established connection between gut microbiota and depression post-MI, this relationship remains incompletely understood.
METHODS AND ANALYSIS: This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) 2020 statement. Beginning from inception to October 2023, a systematic search will be conducted across eight electronic databases, including PubMed, MEDLINE, Scopus, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure, and China Biomedical Literature Database. Pre-selected studies will be independently assessed by two researchers following a standard inclusion, data extraction and quality assessment protocol. The primary outcome measures are differences in the profile of gut microbiota and rating scale scores for depression. Fixed-effects models will be used when both clinical heterogeneity and statistical heterogeneity are low, otherwise random-effects models will be used. Furthermore, subgroup analyses will be conducted on the depression severity of the participants using the same psychiatric scales employed, study type and geographic region. Random forest plot runs and research-related statistical analyses will be carried out using Rev Man V.5.3 software.
EXPECTED RESULTS: This study will identify the association between the gut microbiota and the onset of depression post-MI, and provide evidence for the use of probiotics as an adjunctive treatment for depression post-MI.
TRIAL REGISTRATION: Prospero registration number: CRD42023444026.
Structural epilepsy is a chronic neurologic condition that may be caused by in utero malformations of cortical development (MCD) or post-natal brain injuries resulting in encephalomalacia. We hypothesized that the timing of epileptogenic insult would lead to distinct electrographic seizure patterns. Specifically, we predicted that later life insults would lead to longer duration seizures with higher proportion of focal: focal to bilateral tonic-clonic (FBTC) seizures and low rates of bihemispheric onset seizures, as compared to early life insults. We performed a retrospective chart review of 70 adult patients - 33 with epilepsy secondary to brain injury (9 with injury occurring before 16 years and 24 with injury occurring at or after 16 years) with resultant encephalomalacia on MR imaging and 37 with epilepsy secondary to MCD - admitted to the University of Pittsburgh Epilepsy Monitoring Unit for presurgical evaluation. There were no significant differences in duration of epilepsy or number of trialed seizure medications between the groups. We examined scalp EEG data for all patients, as well as intracranial EEG data in a subset. We analyzed seizure duration, seizure frequency, and seizure type (focal, FBTC, and bihemispheric onset) in three cohorts: MCD patients, patients with brain injury occurring in early life (<16 years old), and patients with brain injury occurring in later life (≥16 years old). Patients with later life brain injury had significantly longer and less frequent seizures as compared to MCD cohorts. There were no differences between MCD and early life brain injury cohorts. Seizure duration findings were corroborated in a subset of patients who additionally underwent intracranial EEG monitoring. Additionally, later life brain injury patients had significantly different seizure types as compared to MCD cohorts, with high rates of FBTC and low rates of bihemispheric onset. Again, there was no significant differences in seizure type between early life brain injury and MCD cohorts. These novel findings indicate the relevance of timing of epileptogenic insult on the electrophysiological characteristics of structural epilepsies.