Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioinformatics analysis of markers based on m6A related to prognosis combined with immune invasion of renal clear cell carcinoma

The incidence rate of renal cell carcinoma (RCC) is about 3% of all adult cancers. Of these, the Kidney clear cell renal cell carcinoma (KIRC) is the most common type, accounting for about 70%–75% of RCC. KIRC is difficult to be detected in time clinically. KIRC still has no effective treatment at this stage. We combined high‐throughput bioinformatics analysis to obtained the structural sequence transcriptome data, relevant clinical information, and m6A gene map of KIRC patients from genomics TCGA database. Pearson's correlation analysis was used to explore m6A related gene long noncoding RNAs (lncRNAs), and then univariate Cox regression analysis was performed to screen the prognostic role of KIRC patients. Lasso–Cox regression was performed to establish the lncRNAs risk model associated with m6 A.LINC02154 and AC016773.2, Z98200.2, AL161782.1, EMX2OS, AC021483.2, CD27‐AS1, AC006213.3 were iidentif. Compared with the low‐risk group, the overall survival of patients in the high‐risk group was significantly worse. Analyzing whether there are differences in immune cells between high‐risk and low‐risk subgroups. There were CD4 memory resting, Monocytes, Macrophages M1, Dendritic cells activated, Mast cells resting, which had higher infiltrations in the low‐risk group. We performed Go enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and gene set enrichment analysis enrichment analysis. Overall, our results suggest that the component of m6A‐related lncRNAs in the prognostic signal may be a key mediator in the immune microenvironment of KIRC, which represents a promising therapeutic effect.
The effects of fenugreek seed extract supplementation in patients with Alzheimer's disease: A randomized, double‐blind, placebo‐controlled trial

The aim of the current randomized control trial (RCT) study was to investigate the effects of fenugreek seed extract on memory, depression, quality of life, blood pressure, and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in adult AD patients. This randomized clinical trial was conducted in geriatric homes in Iran. The study participants included 82 AD patients with mild‐to‐moderate memory deficit. Patients in the intervention group received 5 cc of fenugreek seed extract for 4 months and subjects in the control group received a placebo. Memory, depression, quality of life, and BP levels, as well as serum MDA and TAC, were assessed before and after the intervention. There was a significant increase in serum levels of TAC (p < 0.001) and a reduction in serum MDA status (p < 0.001) after 4 months of fenugreek seed extract supplementation. In addition, increasing levels of memory (p < 0.001) and quality of life (p < 0.001), as well as reduction of depression (p = 0.002), systolic BP (p < 0.001), and diastolic BP (p < 0.001) levels were detected in the intervention group compared with baseline. Fenugreek seed extract supplementation in AD patients shows promising positive effects on memory, quality of life, BP, and selective oxidative indices levels.
Applying minimally invasive biomarkers of chronic stress across complex ecological contexts

Chronic stress is both theoretically and methodologically challenging to operationalize through biomarkers. Yet minimally invasive, field‐friendly biomarkers of chronic stress are valuable in research linking biology and culture, seeking to understand differential patterns of human development across ecological contexts, and exploring the evolution of human sociality. For human biologists, a central question in measurement and interpretation of biomarkers is how stress‐responsive physiological systems are regulated across diverse human ecologies. This article aims to describe a conditional toolkit for human biologists interested in the study of chronic stress, highlighting a mix of longstanding and novel biomarkers, with special focus on hair/fingernail cortisol, latent herpesvirus antibodies, allostatic load indices, and serial/ambulatory data collection approaches. Future trends in chronic stress biomarker research, including epigenetic approaches, are briefly considered. This overview considers: (1) challenges in separating a distinctly psychosocial dimension of chronic stress from adversity more broadly; (2) essential characteristics of human ecology that shape interpretation; (3) retrospective vs. longitudinal sampling; (4) the role of age, developmental effects, and local biologies; (5) different timescales of chronicity; and (6) the role of culture.
Fear Avoidance Beliefs in Upper-Extremity Musculoskeletal Pain Conditions: Secondary Analysis of a Prospective Clinical Study on Digital Care Programs

Abstract Background Fear-avoidance beliefs (FAB) have been associated with poorer prognosis and decreased adherence to exercise-based treatments in musculoskeletal (MSK) pain. However, the impact of high FAB on adherence and outcomes in upper extremity MSK (UEMSK) pain is poorly explored, particularly through exercise-based digital care programs (DCP). Objective Assess the adherence levels, clinical outcomes and satisfaction in patients with UEMSK pain and elevated FAB after a fully remote multimodal DCP. Associations between FABQ-PA and clinical outcomes were conducted. Methods Secondary analysis of an ongoing clinical trial. Participants with UEMSK pain (shoulder, elbow, and wrist/hand) and elevated FAB-physical activity (FABQ-PA ≥ 15) were included. Adherence (completion rate, sessions/week, total exercise time) and mean change in clinical outcomes—disability (QuickDASH), numerical pain score, FABQ-PA, anxiety (GAD-7), and depression (PHQ-9)—between baseline and end-of-program were assessed. Associations between FABQ-PA and clinical outcomes were conducted. Results 520 participants were included, with mean baseline FABQ-PA of 18.02 (SD 2.77). Patients performed on average 29.3 exercise sessions (2.8 sessions/week), totalizing 338.2 exercise minutes. Mean satisfaction was 8.5/10 (SD 1.7). Significant improvements were observed in all clinical outcomes. Higher baseline FAB were associated with higher baseline disability (P < .001), and smaller improvements in disability (P < .001) and pain (P = .001). Higher engagement was associated with greater improvements in FABQ-PA (P = .043) and pain (P = 0.009). Conclusions This study provides evidence of the potential benefits of a structured and multimodal home-based DCP in the management of UEMSK pain conditions in patients with elevated FAB in a real-world context.
NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in NOS1. The activity of the identified NOS1 mutant proteins was assessed by their ability to promote nitrite and cGMP production in vitro. In addition, physiological and pharmacological characterization was carried out in a Nos1-deficient mouse model. We identified five heterozygous NOS1 loss-of-function mutations in six probands with congenital hypogonadotropic hypogonadism (2%), who displayed additional phenotypes including anosmia, hearing loss, and intellectual disability. NOS1 was found to be transiently expressed by GnRH neurons in the nose of both humans and mice, and Nos1 deficiency in mice resulted in dose-dependent defects in sexual maturation as well as in olfaction, hearing, and cognition. The pharmacological inhibition of NO production in postnatal mice revealed a critical time window during which Nos1 activity shaped minipuberty and sexual maturation. Inhaled NO treatment at minipuberty rescued both reproductive and behavioral phenotypes in Nos1-deficient mice. In summary, lack of NOS1 activity led to GnRH deficiency associated with sensory and intellectual comorbidities in humans and mice. NO treatment during minipuberty reversed deficits in sexual maturation, olfaction, and cognition in Nos1 mutant mice, suggesting a potential therapy for humans with NO deficiency. Description The congenital GnRH deficiency caused by altered NOS1 activity can be rescued in mice by nitric oxide therapy at minipuberty. NO problem In 50% of cases of congenital hypogonadotropic hypogonadism (CHH), no gene mutation has been identified. Here, Chachlaki and colleagues identified six patients with CHH and other deficits including anosmia, hearing loss, and intellectual disability, who harbored heterozygous mutations in the nitric oxide synthase 1 (NOS1) gene. These characteristics were also found in Nos1-deficient mice. Nos1 activity in infantile mice was required during minipuberty, and pharmacologically induced NO deficiency in these infantile mice altered sexual maturation. Furthermore, treatment with inhaled NO or a phosphodiesterase 5 inhibitor during minipuberty in mice improved sexual maturation and ameliorated cognitive impairments in adulthood, suggesting a potential therapy for patients suffering from NOS1 deficiency.
Magnetic expansion of Nekrasov theory: the SU(2) pure gauge theory

It is recently claimed by Nekrasov and Shatashvili that the N=2 gauge theories in the {Omega} background with {epsilon}{sub 1}=({h_bar}/2{pi}), {epsilon}{sub 2}=0 are related to the quantization of certain algebraic integrable systems. We study the special case of SU(2) pure gauge theory; the corresponding integrable model is the A{sub 1} Toda model, which reduces to the sine-Gordon quantum mechanics problem. The quantum effects can be expressed as the WKB series written analytically in terms of hypergeometric functions. We obtain the magnetic and dyonic expansions of the Nekrasov theory by studying the property of hypergeometric functions in the magnetic and dyonic regions on the moduli space. We also discuss the relation between the electric-magnetic duality of gauge theory and the action-action duality of the integrable system.
Cisplatin‐induced HSF1‐HSP90 axis enhances the expression of functional PD‐L1 in oral squamous cell carcinoma

Immune checkpoint inhibitor‐based cancer immunotherapy has provided an additional therapeutic option for oral squamous cell carcinoma (OSCC) with recurrence or distant metastases. However, further improvement of OSCC treatment is required to develop the optimal combination or order for chemoradiotherapy and immunotherapy. Along with the accumulation of clinical knowledge and evidence, it is also essential to clarify the biological impact of chemo‐radiotherapeutic agents on the cancer immune microenvironment. In this study, we investigated the effects of cisplatin (CDDP), a key therapeutic agent for OSCC, on programmed death‐ligand 1 (PD‐L1) expression in OSCC lines. Although CDDP treatment increased the surface levels of PD‐L1 on OSCC cell lines, the gene and total protein expression levels of PD‐L1 were not altered. We also demonstrated that the phosphorylation of heat shock factor 1 and heat shock protein 90 was involved in this process. In addition, CDDP‐induced PD‐L1 attenuated the target‐specific cytotoxic T lymphocyte reaction to OSCC. These results provide an immunobiological basis for the response of OSCC to CDDP and will contribute to our biological understanding of the action of novel combination therapy including immunotherapy together with platinum‐based chemotherapy for OSCC.
Non-Equilibrium Thermal Entanglement Dynamics of Heisenberg Systems

The effects of initial conditions and system parameters on entanglement dynamics and asymptotic entanglement for a two-qubit anisotropic XY Heisenberg system in the presence of an inhomogeneous magnetic field and spin-orbit interaction are investigated. We suppose that each qubit interacts with a separate thermal reservoir which is held in its own temperature. The effects of the parameters of the system and environment like spin-orbit interaction and temperature difference of reservoirs are also discussed.
Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDAC. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval : 30.9-61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were two CR and five partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AE) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥3 AE emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AE were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat could be a new therapeutic option in patients with R/R PTCL (clinicaltrials gov. Identifier: NCT02953652).
Metabolomics—a powerful tool in livestock research

Abstract Advancements in the Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) along with recent developments in omics sciences have resulted in a better understanding of molecular mechanisms and pathways associated with the physio-pathological state of the animal. Metabolomics is a post-genomics tool that deals with small molecular metabolites in a given set of time which provides clear information about the status of an organism. Recently many researchers mainly focus their research on metabolomics studies due to its valuable information in the various fields of livestock management and precision dairying. The main aim of the present review is to provide an insight into the current research output from different sources and application of metabolomics in various areas of livestock including nutri-metabolomics, disease diagnosis advancements, reproductive disorders, pharmaco-metabolomics, genomics studies, and dairy production studies. The present review would be helpful in understanding the metabolomics methodologies and use of livestock metabolomics in various areas in a brief way.
Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy‐related cognitive impairment in patients with breast cancer who receive chemotherapy

Chemotherapy‐related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI.
Mortality Associated With Occupational Exposure in Helsinki, Finland—A 24-Year Follow-up

This paper studies the possible combined effect of occupational exposure and chronic airway disease to all-cause and respiratory related mortality in a longitudinal study setting. The results suggest that occupational airborne exposure increases mortality and is even more harmful for those with asthma and COPD coexistence. Objectives Our objective was to study mortality related to different obstructive lung diseases, occupational exposure, and their potential joint effect in a large, randomized population-based cohort. Methods We divided the participants based on the answers to asthma and chronic obstructive pulmonary disease (COPD) diagnoses and occupational exposure and used a combined effects model and compared the results to no asthma or COPD with no occupational exposure. Results High exposure had a hazards ratio (HR) of 1.34 (1.11–1.62) and asthma and COPD coexistence of 1.58 (1.10–2.27). The combined effects of intermediate exposure and coexistence had an HR of 2.20 (1.18–4.09), high exposure with coexistence of 1.94 (1.10–3.42) for overall mortality, and sub-HR for respiratory-related mortality of 3.21 (1.87–5.50). Conclusions High occupational exposure increased overall but not respiratory-related mortality hazards, while coexisting asthma and COPD overall and respiratory-related hazards of mortality.
Advances in The Application and Research of Magnetic Resonance Diffusion Kurtosis Imaging in The Musculoskeletal System

Magnetic resonance diffusion kurtosis imaging (DKI) is an emerging magnetic resonance imaging (MRI) technique that can reflect microstructural changes in tissue through non‐Gaussian diffusion of water molecules. Compared to traditional diffusion weighted imaging (DWI), the DKI model has shown greater sensitivity for diagnosis of musculoskeletal diseases and can help formulate more reasonable treatment plans. Moreover, DKI is an important auxiliary examination for evaluation of the motor function of the musculoskeletal system. This article briefly introduces the basic principles of DKI and reviews the application and research of DKI in the evaluation of disorders of the musculoskeletal system (including bone tumors, soft tissue tumors, spinal lesions, chronic musculoskeletal diseases, musculoskeletal trauma, and developmental disorders) as well as the normal musculoskeletal tissues.
Gas Chromatography – Ion Mobility Spectrometry as a tool for quick detection of hazardous volatile organic compounds in indoor and ambient air: A university campus case study

Society’s concerns about the citizens’ exposure to possibly dangerous environments have recently risen; nevertheless, the assessment of indoor air quality still represents a major contemporary challenge. The volatile organic compounds (VOCs) are among the main factors responsible for deteriorating air quality conditions. These analytes are very common in daily-use environments and they can be extremely hazardous to human health, even at trace concentrations levels. For these reasons, their quick detection, identification, and quantification are crucial tasks, especially for indoor and heavily-populated scenarios, where the exposure time is usually quite long. In this work, a Gas Chromatography – Ion Mobility Spectrometry (GC-IMS) device was used for continuous monitoring indoor and ambient air environments at a large-scale, due to its outstanding levels of sensibility, selectivity, analytical flexibility, and almost real-time monitoring capability. A total of 496 spectra were collected from 15 locations of a university campus and posteriorly analysed. Overall, 23 compounds were identified among the 31 detected. Some of them, like Ethanol and 2-Propanol, were reported as being very hazardous to the human organism, especially in indoor environments. The achieved results confirmed the suitability of GC-IMS technology for air quality assessment and monitoring of VOCs and, more importantly, proved how dangerous indoor environments can be in scenarios of continuous exposure.
Acinetobacter baumannii: Pathogenesis, virulence factors, novel therapeutic options and mechanisms of resistance to antimicrobial agents with emphasis on tigecycline

Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia and wound infections. A wide range of virulence factors are responsible for pathogenesis and high mortality of A. baumannii including outer membrane proteins, lipopolysaccharide, capsule, phospholipase, nutrient‐ acquisition systems, efflux pumps, protein secretion systems, quarom sensing and biofilm production. These virulence factors contribute in pathogen survival in stressful conditions and antimicrobial resistance.
Quantum Cosmology Near Two Dimensions

We consider a Weyl-invariant formulation of gravity with a cosmological constant in $d$-dimensional spacetime and show that near two dimensions the classical action reduces to the timelike Liouville action. We show that the renormalized cosmological term leads to a nonlocal quantum momentum tensor which satisfies the Ward identities in a nontrivial way. The resulting evolution equations for an isotropic, homogeneous universe lead to slowly decaying vacuum energy and power-law expansion. We outline the implications for the cosmological constant problem, inflation, and dark energy.
The impact of first wave of the SARS-CoV-2 2019 pandemic in Poland on characteristics and outcomes of patients hospitalized due to stable coronary artery disease

Background An investigation of baseline characteristics, treatment, and outcomes in patients with stable coronary disease after the first wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may provide valuable data and is beneficial for public health strategy in upcoming years. Methods A multi-institutional registry, including 10 cardiology departments, was searched for patients admitted from June 2020 to October 2020. The baseline characteristics (age, gender, symptoms, comorbidities), treatment (non-invasive, invasive, surgical), and hospitalization outcome (mortality, myocardial infarction, stroke, composite endpoint — major adverse cardiac and cerebrovascular events [MACCE]) were evaluated. The comparison was made to parameters presented by patients from the same timeframe in 2019 (June–October). Multivariable analysis was performed. Results Number of hospitalized stable patients following lockdown was lower (2498 vs. 1903; p < 0.0001). They were younger (68.0 vs. 69.0; p < 0.019), more likely to present with hypertension (88.5% vs. 77.5%; p < 0.0001), diabetes (35.7% vs. 31.5%; p = 0.003), hyperlipidemia (67.9% vs. 55.4%; p < 0.0001), obesity (35.8% vs. 31.3%; p = 0.002), and more pronounced symptoms (Canadian Cardiovascular Society [CCS] III and CCS class IV angina: 30.4% vs. 26.5%; p = 0.005). They underwent percutaneous treatment more often (35.0% vs. 25.9%; p < 0.0001) and were less likely to be referred for surgery (3.7% vs. 4.9%; p = 0.0001). There were no significant differences in hospitalization outcome. New York Heart Association (NYHA) class IV for heart failure was a risk factor for both mortality and MACCE in multivariate analysis. Conclusions The SARS-CoV-2 2019 pandemic affected the characteristics and hospitalization course of stable angina patients hospitalized following the first wave. The hospitalization outcome was similar in the analyzed time intervals. The higher prevalence of comorbidities raises concern regarding upcoming years.