anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Hepatic encephalopathy (HE) is a debilitating complication associated with both acute and chronic liver injury. It is associated with a greater risk of death than any other significant hepatic decompensation event. It manifests as a wide spectrum of neuropsychological abnormalities ranging from subtle impairments in higher cognitive function, to confusion and coma. The pathophysiological role of ammonia in the development of HE is well known, but there is increasing recognition that the gut microbiome, gut-derived systemic inflammation and development of infection can serve as drivers of HE in patients with cirrhosis. The development of HE portents to the severity of cirrhosis and the prognosis is poor without liver transplantation. A referral for liver transplantation should therefore be considered early in those who are eligible. This review covers the pragmatic assessment of HE in patients with cirrhosis, as well as the current evidence base for the best practice management of HE in such patients.
Itraconazole showed no evidence of carcinogenicity potential in mice treated orally for 23 months at dosage levels up to 80 mg/kg/day(approximately 10 times the maximum recommended human dose [MRHD]). Male rats treated with 25 mg/kg/day (3.1 times the MRHD) had a slightly increased incidence of soft tissue sarcoma. These sarcomas may have been a consequence of hypercholesterolemia, which is a response of rats, but not dogs or humans, to chronic itraconazole administration. Female rats treated with 50 mg/kg/day (6.25 times the MRHD) had an increased incidence of squamous cell carcinoma of the lung (2/50) as compared to the untreated group. Although the occurrence of squamous cell carcinoma in the lung is extremely uncommon in untreated rats, the increase in this study was not statistically significant.  
Itraconazole produced no mutagenic effects when assayed in DNA repair test (unscheduled DNA synthesis) in primary rat hepatocytes, in Ames tests with Salmonella typhimurium (6 strains) and Escherichia coli, in the mouse lymphoma gene mutation tests, in a sex-linked recessive lethal mutation (Drosophila melanogaster) test, in chromosome aberration tests in human lymphocytes, in a cell transformation test with C3H/10T½ C18 mouse embryo fibroblasts cells, in a dominant lethal mutation test in male and female mice, and in micronucleus tests in mice and rats.

Itraconazole did not affect the fertility of male or female rats treated orally with dosage levels of up to 40 mg/kg/day (5 times the MRHD), even though parental toxicity was present at this dosage level. More severe signs of parental toxicity, including death, were present in the next higher dosage level, 160 mg/kg/day (20 times the MRHD).
A flow sensor sub-assembly for sensing flow of a fluid medicament includes a flow tube having a flow tube inlet and a flow tube outlet and an acoustic transmission ratio. The medicament flows through the flow tube. The first piezoelectric element is arranged at an upstream position of the flow tube and the second piezoelectric element is arranged at a downstream position of the flow tube such that the first piezoelectric element and the second piezoelectric element are mounted apart from each other by a preset distance. An absorber shroud surrounds the flow tube. The absorber sheath has an upstream end and a downstream end. The absorber sheath is constructed of a material having a different acoustic transmission ratio than the flow tube.
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 will coexist with humans for a long time, and it is therefore important to develop effective treatments for coronavirus disease 2019 (COVID-19). Recent studies have demonstrated that antiviral therapy is a key factor in preventing patients from progressing to severe disease, even death. Effective and affordable antiviral medications are essential for disease treatment and are urgently needed. Azvudine, a nucleoside analogue, is a potential low-cost candidate with few drug interactions. However, validation of high-quality clinical studies is still limited.
METHODS: This is a multicentre, randomized, double-blind, placebo-controlled phase III clinical trial involving 1096 adult patients with mild-to-moderate symptoms of COVID-19 who are at high risk for progression to severe COVID-19. Patients will be randomized to (1) receive azvudine tablets 5 mg daily for a maximum of 7 days or (2) receive placebo five tablets daily. All participants will be permitted to use a standard treatment strategy except antiviral therapy beyond the investigational medications. The primary outcome will be the ratio of COVID-19-related critical illness and all-cause mortality among the two groups within 28 days.
DISCUSSION: The purpose of this clinical trial is to determine whether azvudine can prevent patients at risk of severe disease from progressing to critical illness and death, and the results will identify whether azvudine is an effective and affordable antiviral treatment option for COVID-19.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05689034. Registered on 18 January 2023.
There are currently no available data on the relationship between sonographic temporary nephromegaly in children during their first febrile urinary tract infection (fUTI) and recurrent fUTI. For this analysis, a multicenter retrospective cohort study of 343 children who underwent renal ultrasound during their first fUTI was conducted between 2013 and 2020. Sonographic temporary nephromegaly was defined as increased renal length during the initial fUTI, followed by normal renal length after antibiotic treatment. Compared with children without sonographic temporary nephromegaly (n = 307), the duration of fever and intravenous antibiotics was significantly longer, and C-reactive protein, creatinine, and the proportion of children who had recurrent fUTI were significantly higher, in those with sonographic temporary nephromegaly (n = 36). In an additional analysis of 100 patients who received voiding cystourethrography, a logistic regression model confirmed that the odds of vesicoureteral reflux (VUR) were significantly higher in children with temporary nephromegaly or those who experienced fUTI recurrence. In nine out of 16 children with VUR who had temporary nephromegaly, the reason for receiving voiding cystourethrography was recurrent fUTI. Our results suggest that sonographic temporary nephromegaly during an initial fUTI is predictive for recurrence and VUR, and that in children with temporary nephromegaly, VUR may be detectable before fUTI recurrence.
The initiation reactions of DNA synthesis are central processes during human chromosomal DNA replication. They are separated into two main processes: the initiation events at replication origins, the start of the leading strand synthesis for each replicon, and the numerous initiation events taking place during lagging strand DNA synthesis. In addition, a third mechanism is the re-initiation of DNA synthesis after replication fork stalling, which takes place when DNA lesions hinder the progression of DNA synthesis. The initiation of leading strand synthesis at replication origins is regulated at multiple levels, from the origin recognition to the assembly and activation of replicative helicase, the Cdc45-MCM2-7-GINS (CMG) complex. In addition, the multiple interactions of the CMG complex with the eukaryotic replicative DNA polymerases, DNA polymerase α-primase, DNA polymerase δ and ε, at replication forks play pivotal roles in the mechanism of the initiation reactions of leading and lagging strand DNA synthesis. These interactions are also important for the initiation of signalling at unperturbed and stalled replication forks, "replication stress" events, via ATR (ATM-Rad 3-related protein kinase). These processes are essential for the accurate transfer of the cells' genetic information to their daughters. Thus, failures and dysfunctions in these processes give rise to genome instability causing genetic diseases, including cancer. In their influential review "Hallmarks of Cancer: New Dimensions", Hanahan and Weinberg (2022) therefore call genome instability a fundamental function in the development process of cancer cells. In recent years, the understanding of the initiation processes and mechanisms of human DNA replication has made substantial progress at all levels, which will be discussed in the review.
Abemaciclib 150 milligram (mg) administered every 12 hours, orally, cycle 1 and then in cycle 2. Participants may continue to receive treatment until discontinuation criteria are met. One cycle is defined as 28 days. (Cycle 1: 32 days), with modifications during Cycle 1 to enable pharmacokinetic (PK) sampling following a single dose and repeated doses.
At least 40 SNP (single nucleotide polymorphisms)increase the risk of PCa. The individual risk of PCa accumulates with the increasing number of these genetic variants. The risk is doubled if patient has familial disposition as well. In retrospective studies, non-genetic risk-prediction models were compared to risk-prediction models containing both non-genetic factors and SNPs analyses. The genetic models had a significantly higher specificity than the non-genetic models. It has been argued that genetic PCa risk assessment could reduce the inexpedient use of PSA tests, saving it for patients at high risk of PCa.
OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are lacking.
METHODS: We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC (eTNBC) and 415 metastatic TNBC (mTNBC) patients] who were treated at Fudan University Shanghai Cancer Center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.
RESULTS: The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1% (47/465). The median overall survival (OS) in the mTNBC cohort was 27.2 months [95% confidence interval (CI), 24.4-30.2 months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like (MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.
CONCLUSIONS: Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.
A composition is provided that includes a polymer matrix. A core having a core surface is embedded within the polymer matrix. A polymeric ligand passivates the core surface and has a moiety Y, where Y is a Diels-Alder group of a diene or dienophile. A polymeric linker has a complementary Diels-Alder group diene or dienophile to moiety Y and forms a Diels-Alder bond with the moiety Y. A composition is also provided that includes polymer matrix having a matrix surface. A core having a core surface is present on the matrix surface. A polymeric ligand passivates the core surface and has a moiety Y, where Y is Diels-Alder group of a diene or dienophile. The polymer matrix and polymeric ligand together define a matrix-ligand Flory-Huggins binary interaction function greater than 0.
Patients randomized to the intervention group will receive inulin supplementation for 14 days, preceding the surgery. Inulin will be given at a dosage of 10g/day divided in two doses.
The Tai Chi program was based on the classical Yang Style. Patients participated in 60-minute Tai Chi sessions twice a week for 12 weeks. Each session included warm up and review of Tai Chi principles and techniques; Tai Chi exercises; breathing techniques; and various relaxation methods. The classes were taught by a Tai Chi master with over 20 years' experience conducting Tai Chi Mind-Body exercise programs. Several modifications were developed to achieve the physical and mental goals of the study for knee OA, accommodate knee OA symptoms and limit dropouts. Subjects were instructed to practice Tai Chi at least 20 minutes a day at home and encouraged to maintain their usual physical activities, but not to participate in additional new strength training other than their Tai Chi exercises.
This study will include two major populations: (1) the Adult Repeat Cross Sectional study (ARCS) will involve 125 healthy Kenya-residents male and female aged 18 years and above; and (2) the Pediatric Infant Cohort (PIC) will include 300 healthy male and female infants who are residents of Kenya. In addition, 20 healthy adult US residents, who have no self-reported history of malaria exposure, infection or travel to malaria endemic areas of the world, will serve as Malaria Naive Negative Controls (MNNC). The adult (ARCS) study will consist of 6 venous blood donations to be completed in one year. The primary outcome of the ACRS is to determine the stability of Immune responses to MSP-1 who are clinically protected against P. falciparum infections and the secondary outcome is to measure the level and stability of MSP-1 specific IIA activity, MSP-1 specific T-cell memory phenotypes and immune functions and lastly, to determine the MSP-1 genotypes. The PIC study is both home and clinic-based. The overall duration of this study will be three years. The subjects will be recruited during their routine immunizations visit. The data and sample collections consist of monthly home-visits interspersed by clinic-visits every 6 months until the child reaches 3 years old. The primary outcome of the PIC study is to evaluate the development of humoral and cellular immunity to MSP-1 in healthy children in relation to their history of P. falciparum infections, number of episodes of uncomplicated acute malarial infections in the first 3 years of life and secondary outcome is to measure the acquisition of MSP-1 specific IIA activity, shifts in T-cell memory phenotypes and amalaira-specific immunity and their association with the history of exposure to P. falciparum MSP-1 alleleic variants. For the MNNS study, the primary objective is to optimize molecular and immunologic assays to be used in Kenya and to determine background level responses in healthy adult and the secondary outcomes aims to measure the level of MSP-1 specific IIA-activity, T-cell memory phenotypes and any non-specific immunity to malaria antigens and to provide negative control DNA for P. falciparum detection and genotyping studies. The result of these studies will provide insight into how the frequency and intensity of prior malaria infection and antigenic polymorphism influence the generation and maintenance of T-cell memory and AB responses to merozoite surface proteins in humans.
Anterior hip dislocations as compared to posterior, rarely occurs. Nevertheless, it is important to be prepared to manage it. Physical examination and imaging are crucial in detecting this type of dislocation and ruling out any associated fractures. The most important thing is not delaying reduction which is done in a closed manner preferably in the operating room and under general anesthesia. Post-operative complications should be monitored. As for rehabilitation it is still debated and no consensus was reached.
End-stage kidney disease (ESKD) is fatal without treatment by kidney replacement therapies (KRTs). However, access to these treatment modalities can be problematic given the high costs. This systematic review (SR) aims to provide an updated economic evaluation of pairwise comparisons of KRTs and the implications for the proportion of patients with access to the KRT modalities, i.e., kidney transplantation (KT), hemodialysis (HD), and peritoneal dialysis (PD). This SR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020. We searched studies in PubMed, Embase, Scopus, and Cost Effectiveness Analysis (CEA) registry, from inception to March 2023. Thirteen studies were included with pairwise comparisons among three KRTs, with varying proportions of patients for each modality. Seven studies were from high-income countries, including five from Europe. Summary findings are presented on a cost-effectiveness plane and incremental net benefit (INB). KT was the most cost-effective intervention across the pairwise comparisons. KT and PD were both more cost-effective alternatives to HD. HD was more costly and less effective than PD in all studies except one. Concurrent efforts to increase both KT and PD represented the best scenario to improve treatment options for ESKD patients.
The invention belongs to the technical field of biomedicine, and provides a function of a DNA damage repair related gene in cervical cancer, wherein a molecular biology approach is adopted to confirm that the expression level of a gene TIMELESS has obvious correlation with the cervical cancer progress for the first time, and the gene TIMELESS is hardly expressed in normal cervical tissues. The invention screens siRNA taking TIMELESS as a target spot at the gene level, and provides an siRNA sequence capable of efficiently and specifically knocking down TIMELESS expression. The invention also relates to application of the TIMELESS siRNA and the pharmaceutical composition in treating cervical cancer. The pharmaceutical composition refers to the siRNA nucleotide fragment containing effective dose and pharmaceutically acceptable excipient. The TIMELESS siRNA can obviously inhibit the proliferation and the cloning formation capability of cervical cancer cells, promote the apoptosis and the aging of the cervical cancer cells and promote the cis-platinum sensitivity of the cervical cancer SiHa cells. The siRNA in the invention can up-regulate the expression of clear Caspase-3 and p21, and finally promote the apoptosis and the aging of cervical cancer cells.
FIELD: medicine, biochemical pharmacology. SUBSTANCE: invention relates to the developed pharmaceutical composition based on dopamine-generating substance, in part, dihydroxyphenyl-alanine. This substance is a dopamine precursor and it is taken in composition in the amount 2.5; 4.5; 20.0; 50.0 or 90.0 mg/1000 mg of accessory substances, for example, starch, sucrose, lactose and so on and sunflower, peanut oil, cod fish liver and others also. Also, composition has additionally antioxidant taken in the amount 4.0-20.0 mg and glucocortico-steroid taken in the amount 0.01-10.0 mg. Invention involves also method of evaluation of individual effectiveness of the composition. This method is developed on the basis of adrenographic method of examination. Method involves realization of functional test by administration in patient one-half, one- or two-fold dose of composition with maximal dose of dopamine-generating substance. EFFECT: broadened arsenal of agents for control of disorders of sympathetic-adrenal system of body. 9 cl, 6 ex
Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.
The present invention relates to a hair care agents containing selected non-ionic polymers and cationic silicones. For modern hair care agents, attempts are increasingly made to apply the product to the keratin fibres in the form of a foam. The foam should be creamy and fine-pored, simultaneously have a certain volume and be sufficiently stable such that it remains stable when it is worked into the keratin fibres. Until now these requirements could only be fulfilled with high quantities of tensides and/or propellants. This type of use is made even more difficult when no propellants should be used and the foam should be produced instead in pump dispensers by means of special nozzles. This frequently results only in relatively aqueous, large-pored foam with little stability. The more care ingredients are contained in the aqueous composition, the poorer the quality of the foam.
Participants with pre-existing ART regimen of EFV will take CVC 300 mg. Participants with all other pre-existing ARTs will take CVC 150 mg.
Working memory (WM) is the ability to hold information actively in mind and is fundamental for higher-order cognition. This pilot study aims to (1) evaluate the efficacy of WM training in older adults with MCI and (2) understand if and how it works. The study will use behavioral and brain imaging assessments to see whether WM training changes how participants learn and remember information. Functional magnetic resonance imaging (fMRI) and functional near infrared spectroscopy (fNIRS) methods will be used. The study will also use cognitive tests and questionnaires to determine whether participants' cognitive abilities change with training. The study will enroll participants with a diagnosis of MCI as well as cognitively intact older adults (healthy controls, HC).
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in poor prognosis and low 5-year survival rates. While early evidence suggests increased long-term survival in those with screen-detected resectable cancers, surveillance imaging is currently only recommended for individuals with a lifetime risk of PDAC ≥ 5%. Identification of risk factors for PDAC provides opportunities for early detection, risk reducing interventions, and targeted therapies, thus potentially improving patient outcomes. Here, we summarize modifiable and non-modifiable risk factors for PDAC. We review hereditary cancer syndromes associated with risk for PDAC and their implications for patients and their relatives. In addition, other biologically relevant pathways and environmental and lifestyle risk factors are discussed. Future work may focus on elucidating additional genetic, environmental, and lifestyle risk factors that may modify PDAC risk to continue to identify individuals at increased risk for PDAC who may benefit from surveillance and risk reducing interventions.