anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention. The invention also relates to a composition or therapeutic combination comprising an antibody-drug conjugate or antibody-oligonucleotide conjugate and the first proteinaceous molecule of the invention. An aspect of the invention relates to a pharmaceutical composition comprising the composition or the antibody-drug conjugate of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the therapeutic combination or the composition or the antibody-drug conjugate or the pharmaceutical composition of the invention, for use as a medicament. The invention also relates to the therapeutic combination of the invention for use in the treatment or prophylaxis of a cancer.
The protocol comprises of 24 consecutive Intermittent Hypoxic Training (IHT) sessions, 3 sessions per week within a two months' period. Subjects will train according to individualized training protocol.
Participants with CPP having body weight ≥20 kg will receive the recommended dose of leuprorelin acetate depot 11.25 mg subcutaneous administration (SC) every 12 weeks based on the standard of 30～180ug/kg/4weeks for the 24-week Treatment Period. It is not recommended to exceed the dose above 180 μg/kg.
Hypertrophic scar (HS) is a chronic inflammatory skin disorder characterized by excessive deposition of extracellular matrix, and the mechanisms underlying their formation remain poorly understood. We analysed scRNA-seq data from samples of normal skin and HS. Using the hdWGCNA method, key gene modules of fibroblasts in HS were identified. Non-negative matrix factorization was employed to perform subtype analysis of HS patients using these gene modules. Multiple machine learning algorithms were applied to screen and validate accurate gene signatures for identifying and predicting HS, and a convolutional neural network (CNN) based on deep learning was established and validated. Quantitative reverse transcription-polymerase chain reaction and western blotting were performed to measure mRNA and protein expression. Immunofluorescence was used for gene localization analysis, and biological features were assessed through CCK8 and wound healing assay. Single-cell sequencing revealed distinct subpopulations of fibroblasts in HS. HdWGCNA identified key gene characteristics of this population, and pseudotime analysis was conducted to investigate gene variation during fibroblast differentiation. By employing various machine learning algorithms, the gene range was narrowed down to three key genes. A CNN was trained using the expression of these key genes and immune cell infiltration, enabling diagnosis and prediction of HS. Functional experiments demonstrated that THBS2 is associated with fibroblast proliferation and migration in HS and affects the formation and development of HS through the TGFβ1/P-Smad2/3 pathway. Our study identifies unique fibroblast subpopulations closely associated with HS and provides biomarkers for the diagnosis and treatment of HS.
It has been shown that adult human skin cells or human blood cells can be reprogrammed to become stem cells. This type of stem cell is called an induced Pluripotent Stem Cell (iPSC).It has been shown specifically that this type of stem cell can be produced from adult human skin cells or blood cells can in turn be converted into Retinal Pigment Epithelial (RPE) cells. These RPE cells are a very important cell type in the human retina that are abnormal and ultimately lost in Age-related Macular Degeneration (AMD). Although it has been shown to be possible to make RPE cells from adult human skin, it has not been done to a level to fulfil regulatory requirements for human transplantation in AMD.

This is a feasibility study involving 10 patients. The efficiency of creating an iPSC-Derived RPE cells from a patient's own skin or blood will be examined. A sample size of 10 patients will allow us to potentially consolidate the safety and efficacy of this method in order to create these cells within the context of a future transplantation trial.
BACKGROUND: It is unclear whether laparoscopic hepatectomy (LH) for hepatolithiasis confers better clinical benefit and lower hospital costs than open hepatectomy (OH). This study aim to evaluate the clinical and economic value of LH versus OH.
METHODS: Patients undergoing OH or LH for primary hepatolithiasis at Yijishan Hospital of Wannan Medical College between 2015 and 2022 were divided into OH group and LH group. Propensity score matching (PSM) was used to balance the baseline data. Deviation-based cost modelling and weighted average median cost (WAMC) were used to assess and compare the economic value.
RESULTS: A total of 853 patients were identified. After exclusions, 403 patients with primary hepatolithiasis underwent anatomical hepatectomy (OH n=143; LH n=260). PSM resulted in 2 groups of 100 patients each. Although LH required a longer median operation duration compared with OH (285.0 versus 240.0 min, respectively, P<0.001), LH patients had fewer wound infections, fewer pre-discharge overall complications (26 versus 43%, respectively, P=0.009), and shorter median postoperative hospital stays (8.0 versus 12.0 days, respectively, P<0.001). No differences were found in blood loss, major complications, stone clearance, and mortality between the two matched groups. However, the median overall hospital cost of LH was significantly higher than that of OH (CNY¥52,196.1 versus 45,349.5, respectively, P=0.007). Although LH patients had shorter median postoperative hospital stays and fewer complications than OH patients, the WAMC was still higher for the LH group than for the OH group with an increase of CNY¥9,755.2 per patient undergoing LH.
CONCLUSION: The overall clinical benefit of LH for hepatolithiasis is comparable or even superior to that of OH, but with an economic disadvantage. There is a need to effectively reduce the hospital costs of LH and the gap between costs and diagnosis-related group reimbursement to promote its adoption.
Solute carrier family 12 member 8 (SLC12A8) is a nicotinamide mononucleotide transporter. Despite emerging evidence supporting its potential involvement in oncogenesis, a systematic pan-cancer analysis of SLC12A8 has not been performed. Thus, this research aimed to explore the prognostic implications of SLC12A8 and assess its possible immune-related functions across 33 different tumor types. And multiple datasets were retrieved from the databases of TCGA, GTEx, Broad Institute CCLE, TISCH, HPA, and GDSC2. After this data acquisition, bioinformatics analyses were conducted to assess the potential involvement of SLC12A8 in cancer pathogenesis. These analyses focused on examining the relationship between SLC12A8 and prognosis, drug sensitivity, chemotherapy response, immune checkpoints (ICPs), immune cell infiltration, and immunotherapy efficacy across various tumor types. Furthermore, experimental methods such as EdU assay, wound healing assay, and transwell assay were conducted to evaluate the cell proliferative and invasive abilities. Finally, the data analysis demonstrated that SLC12A8 was differentially expressed and predicted unfavorable survival outcomes in the majority of the tumor types in the TCGA dataset. Furthermore, a notable upregulation in the expression of SLC12A8 mRNA and protein was observed in cancer tissues compared to normal tissues. Additionally, the SLC12A8 levels demonstrated a strong association with ICPs, chemokines, immune-activating genes, immune-suppressive genes, chemokine receptors, chemotherapy response, and immunotherapy efficacy. In vitro experiments substantiated that knockdown of SLC12A8 restricted the malignant phenotypes of MDA-MB-231 and BT-549 cells. So SLC12A8 holds promise as a cancer biomarker with the capacity to interact with other ICPs to synergistically regulate the immune microenvironment. Thus, the identification of SLC12A8 contributes to the development of novel therapeutic strategies for enhancing the efficacy of immunotherapy.
Delayed-release (DR) budesonide received expedited approval from the US Food and Drug Administration (FDA) as a treatment for reducing proteinuria in individuals with primary IgA nephropathy (IgAN) who are at significant risk of disease progression. The approval was based on clinical trials primarily involving patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2. However, the efficacy of DR budesonide in reducing kidney function decline, especially in patients with an eGFR less than 30 mL/min/1.73 m2 and proteinuria less than 1 g/d, remains unclear. We report the case of a 43-year-old man with a long-term history of hypertension and biopsy-proven IgAN who experienced a progressive increase in proteinuria and serum creatinine, along with a decline in eGFR to 28 mL/min/1.73 m2 despite maximal supportive management. Following therapy with DR budesonide, a decreasing trend in proteinuria and a stabilization of eGFR were observed in the recent measurements. While initial data suggested the effectiveness of DR budesonide primarily in patients with an eGFR over 30 mL/min/1.73 m2, our case demonstrates the potential of DR budesonide for use in scenarios beyond its currently approved indications. This underscores the need for additional research on patients with advanced stages of chronic kidney disease.
FIELD: agriculture. ^ SUBSTANCE: invention relates to livestock sector, in particular to the field of development and production of fodder additives for mammal livestock. Fodder additive for the period of saplings carrying or for the period of milk production includes extract of fish oil that contains at least one compound of sn-1-O-alkyl glycerol. Additive is intended for modification of lipid and immunological properties of female beestings or their milk. Method for modification of lipid and immunological composition of beestings or milk of mammal livestock during carrying of saplings or in the period of milk production provides for addition of fodder additive in fodder in amount from 2 to 100 mg of composition of sn-1-O-alkyl glycerol per kg of live weight per day. ^ EFFECT: fodder additive for livestock and method of its preparation are proposed. ^ 12 cl, 8 dwg, 3 tbl
Since the advent of anti-PD1 immune checkpoint inhibitor (ICI) immunotherapy, cutaneous melanoma has undergone a true revolution with prolonged survival, as available 5-year updates for progression-free survival and overall survival demonstrate a durable clinical benefit for melanoma patients receiving ICI. However, almost half of patients fail to respond to treatment, or relapse sooner or later after the initial response to therapy. Little is known about the reasons for these failures. The identification of biomarkers seems necessary to better understand this resistance. Among these biomarkers, HLA-DR, a component of MHC II and abnormally expressed in certain tumor types including melanoma for unknown reasons, seems to be an interesting marker. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on the potential interest of HLA-DR expression in melanoma as a predictive biomarker of ICI outcome.
ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.
BACKGROUND: Considering the previous research that suggested that screen time (ST), sleep duration, physical activity (PA), obesity and cardiometabolic risk factors are related, it is essential to identify how these variables are associated over time, to provide knowledge for the development of intervention strategies to promote health in pediatric populations. Also, there is a lack of studies examining these associations longitudinally. The aims of the present study were: (1) to investigate the longitudinal relationships between ST, sleep duration, leisure PA, body mass index (BMI), and cardiometabolic risk score (cMetS) in children and adolescents; and (2) to verify scores and prevalence of cMetS risk zones at baseline and follow-up.
METHODS: This observational longitudinal study included 331 children and adolescents (aged six to 17 years; girls = 57.7%) from schools in a southern city in Brazil. ST, sleep duration, and leisure PA were evaluated by a self-reported questionnaire. BMI was evaluated using the BMI z-scores (Z_BMI). The cMetS was determined by summing sex- and age-specific z-scores of total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, glucose, and systolic blood pressure and dividing it by four. A two-wave cross-lagged model was implemented.
RESULTS: ST, sleep duration, and leisure PA were not associated with cMetS after 2-years. However, it was observed that higher ST at baseline was associated with shorter sleep duration at follow-up (B=-0.074; 95%IC=-0.130; -0.012), while higher Z_BMI from baseline associated with higher cMetS of follow-up (B = 0.154; 95%CI = 0.083;0.226). The reciprocal model of relationships indicated that the variance of ST, sleep time, leisure PA, Z_BMI, and cMetS explained approximately 9%, 14%, 10%, 67% and 22%, respectively, of the model. Individual change scores and prevalence indicated that cMetS had individual changes from 2014 to 2016.
CONCLUSION: Sleep duration, ST and leisure PA were not associated with cMetS after 2 years. ST showed an inverse association with sleep duration, and Z_BMI was positively associated with cMetS after a 2-year follow-up. Finally, the prevalence of no clustering of risk factors increased after two years. These findings suggest the need to promote healthy lifestyle habits from childhood and considering individual factors that can influence cardiometabolic health in children and adolescents.
FIELD: biotechnology; microbiology.SUBSTANCE: group of inventions relates to biotechnology and medical microbiology and includes three objects: a method for producing a set of fluorescent rickettsial and query fever diagnosticums, use thereof for serological diagnostics of rickettsiosis and query fever, a method for serological diagnostics of rickettsiosis and query fever. Method for producing a set of fluorescent diagnosticums of rickettsiae of group of typhus (R.prowazekii, R. typhi), rickettsiae of groups of spotted fever (R.sibirica, R.conorii) and genus Coxiella (Coxiella burnetii) includes preparation of sorbent from formalized lactic acid bacilli with their labeling with inorganic fluorophores, extraction of active protein-lipopolysaccharide complex from corpuscular antigens Rickettsia prowazekii, R. typhi, R.sibirica, R.conorii, Coxiella burnetii combined methods of ultrasonic disintegration of corpuscles and chromatography, attachment of a protein-lipopolysaccharide complex to a fluorescent sorbent by means of a binding reagent and obtaining an end product – set of fluorescent rickettsial and query fever diagnosticums. Kit contains 5 lyophilically dried diagnosticums: fluorescent diagnosticum R.prowazekii, fluorescent diagnosticum R. typhi, fluorescent diagnosticum R.sibirica, fluorescent diagnosticum R.conorii, fluorescent diagnosticum C.burnetii. Obtained fluorescent diagnosticums are correlated by specificity and sensitivity with a reference preparation – "gold standard" of immunofluorescence – (indirect immunofluorescence reaction, IIFR) and are suitable for diagnosing said diseases. Method for serodiagnosis of rickettsiosis and query fever using a kit is carried out in the format of a single-step direct immunofluorescence method involving applying a test serum onto a slide, adding a fluorescent diagnosticum and incubating mixture at 37 °C for 60 minutes. Smear preparations are dried and viewed under the immersion lens of the fluorescent microscope, the results are evaluated by a four-cross system, documentation is carried out by preserving object glass with smears or preservation of photo from microscope on USB-carrier.EFFECT: proposed group of inventions enables accurate and effective serological diagnosis of rickettsiosis and query fever.9 cl, 10 dwg, 2 tbl, 9 ex
The preparation for prevention and regulation of the level of blood triglycerides according to the present invention is based on natural products and is highly effective while its use does not provoke adverse effects. Said preparation includes from 60 to 80 wt. % dry extract of rosemary (Rosmarinus officinalis), where the content of ursolic acid in said rosemary extract is 25 to 45 wt. %, and 20 to 40 wt. % dry extract of bitter melon (Momordica charantia), wherein the content of charantin in said bitter melon extract is 8 to 15 wt. %.
Individuals with physical disabilities show much lower rates of exercise participation than their able-bodied peers. Much of the reason for the low rates of activity among this population comes from the presence of barriers. Lack of motivation, lack of transportation, lack of accessible facilities and equipment, and cost are all factors that discourage exercise participation among those with disabilities. Based on these factors, there is a need for accessible enjoyable exercise options for people with physical disabilities. The smart trainer ergometer (also known as the Advanced Virtual Exercise Environment Device) is comprised of an ergometer with foot and hand pedals, and a visual display in front of the user that can show a variety of scenic pathways.

In our previous protocol (IRB-300001384) we explored the power output curves of people post stroke compared with non-impaired individuals during one arm versus two arm cycling exercise using the smart trainer arm ergometer. The work demonstrated the potential benefit of interactive exercise for those with physical disabilities. The purpose of this study is to examine changes in power output, oxygen consumption, cognitive function, and quality of life after 8 weeks of smart trainer arm ergometry exercise training among individuals who have a stroke-based limb impairment.
BACKGROUND: Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH.
METHODS: Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo.
RESULTS: Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses.
CONCLUSION: Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.
BACKGROUND: Acute kidney injury (AKI) in sepsis patients increases patient mortality. Endothelial cells are important players in the pathophysiology of sepsis-associated AKI (SA-AKI), yet knowledge regarding their spatiotemporal involvement in coagulation disbalance and leukocyte recruitment is lacking. This study investigated the identity and kinetics of responses of different microvascular compartments in kidney cortex in response to SA-AKI.
METHODS: Laser microdissected arterioles, glomeruli, peritubular capillaries, and postcapillary venules from kidneys of mice subjected to cecal ligation and puncture (CLP) were analyzed using RNA sequencing. Differential expression and pathway enrichment analyses identified genes involved in coagulation and inflammation. A selection of these genes was evaluated by RT-qPCR in microvascular compartments of renal biopsies from patients with SA-AKI. The role of two identified genes in lipopolysaccharide-induced endothelial coagulation and inflammatory activation were determined in vitro in HUVEC using siRNA-based gene silencing.
RESULTS: CLP-sepsis in mice induced altered expression of approximately 400 genes in the renal microvasculature, with microvascular compartments exhibiting unique spatiotemporal responses. In mice, changes in gene expression related to coagulation and inflammation were most extensive in glomeruli at early and intermediate time points, with high induction of Plat, Serpine1, Thbd, Icam1, Stat3, and Ifitm3. In human SA-AKI, PROCR and STAT3 were induced in postcapillary venules, while SERPINE1 expression was diminished. IFITM3 was increased in arterioles and glomeruli. In vitro studies revealed that STAT3 and IFITM3 partly control endothelial coagulation and inflammatory activation.
CONCLUSION: Renal microvascular compartments in mice and humans exhibited heterogeneous changes in coagulation- and inflammation-related gene expression in response to SA-AKI. Additional research should aim at understanding the functional consequences of the here described heterogeneous microvascular responses to establish the usefulness of identified genes as therapeutic targets in SA-AKI.