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Integrative multi-criteria decision analysis reveals thyroid-mediated metabolic regulation as a key driver of heat stress resilience in cattle.

Climate change-induced heat stress threatens tropical livestock production. While indigenous breeds are known to be thermotolerant, the underlying physiological mechanisms remain poorly characterized. This study comprehensively evaluated the haematological, biochemical, and hormonal responses of three cattle genotypes (n = 40/group) Holstein Friesian (HF), Brangus (BR), and Kedah-Kelantan (KK) maintained under severe natural heat stress (Temperature-Humidity Index: 79-88). During the peak thermal challenge, HF cattle exhibited significantly elevated leukocyte counts (15.87 ± 0.94 vs. 8.33 ± 0.

Behavioral Modification as a Putative Mediator of Digital Therapeutic Response in Temporomandibular Disorders: Secondary Analysis of a Multicenter Sham-Controlled Randomized Trial.

BACKGROUND: Temporomandibular disorders (TMDs) are common chronic conditions involving orofacial pain and functional limitations. Digital th … reduction thresholds; subgroup comparison by Oral Behaviors Checklist (OBC) modifier status; causal mediation analysis using the potential outcomes framework with bootstrap CIs; week-4 sensitivity analysis; and moderator analysis testing the treatment×Patient Health Questionnaire-4 (PHQ-4) interaction on VAS change. RESULTS: DTx assignment was consistently associat …

HPV status fully mediates sex-related survival differences in oropharyngeal cancer: a population-based analysis with formal interaction testing.

OBJECTIVES: To determine whether sex independently predicts survival in oropharyngeal squamous cell carcinoma and whether human papillomavirus status mediates apparent sex-related survival differences at the population level. METHODS: Population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database (17 Registries, 2018-2021). Multivariable Cox regression and a formal sex-human papillomavirus interaction test (likelihood ratio test) were performed in 19,716 patients with known p16/HPV status. RESULTS: p16-positive disease was more prevalent in males (73.6 pe

Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics.

With the rapid advancement of proteomics, numerous scholars have investigated the intricate relationships between plasma proteins and various diseases. Therefore, this study aims to elucidate the relationship between BDH1 and type 2 diabetes using Mendelian randomization (MR) and to identify novel targets for the prevention and treatment of type 2 diabetes through proteomics. This study primarily employed the Mendelian Randomization (MR) method, leveraging genetic data from numerous large-scale, publicly accessible genome-wide association studies (GWAS). Within this framework, we adopted a two

Serum metabolites and gut microbiota mediate the causal link between anxiety and nonalcoholic fatty liver disease: a Mendelian randomization analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is defined by liver fat accumulation exceeding 5% in individuals who do not consume significant amounts of alcohol. This condition can advance to more severe outcomes, including fibrosis, cirrhosis, and liver cancer. Although numerous factors contribute to the progression of NAFLD, the influence of psychological elements, especially anxiety, remains inadequately explored. METHODS: This study applied Mendelian randomization (MR) using genome-wide association data from 4761 NAFLD cases and 373 227 controls to investigate the causal relationsh

When dark triad rules the moral: How empathy mediates idealism and relativism- a latent profile and pathway analysis in medical training.

Personality factors, empathy and ethical perspectives are key factors in understanding medical students and healthcare professional's framework toward better patient care, medical communication and quality of life. One of these factors are Psychopathy, Machiavellianism, Narcissism and also Idealism and Relativism, however there is limited data evaluating these. The aim of this study was therefore to deeply investigate the links between Dark Traits and Ethics Positioning focusing on the mediating role of Empathy among medical students. Participants (N = 116, M age = 19,13 years, 70,68 % female)

Targeting HSV-1 glycoprotein D through riboflavin-mediated photodynamic therapy: Insights from bioinformatics analysis and in vitro evaluation.

INTRODUCTION: The herpes simplex virus type 1 (HSV-1) causes painful viral lesions in the mucosal and cutaneous areas of the oral cavity as well as the head and neck. photodynamic therapy (PDT) effectively inactivates HSV-1 by targeting multiple structures and molecules without the risk of developing resistant strains. The most significant factor influencing the antiviral efficacy of PDT is the type of photosensitizer used. Therefore, finding more effective photosensitizers is essential. This study utilizes biological databases and bioinformatics tools to investigate computational simulations,

Quinolone resistance in Riemerella anatipestifer from Thai ducks: Mutation analysis of gyrA, parC, and plasmid-mediated quinolone resistance genes.

BACKGROUND AND AIM: Riemerella anatipestifer is a Gram-negative bacterium causing systemic infections in ducks, often treated with quinolones. However, increasing resistance to quinolones poses a threat to effective treatment, and the molecular mechanisms underlying this resistance remain inadequately understood in Thailand. This study aimed to determine the minimum inhibitory concentrations (MICs) of nalidixic acid, ciprofloxacin, and enrofloxacin; identify mutations in the quinolone resistance-determining regions of gyrA and parC; and detect plasmid-mediated quinolone resistance (PMQR) genes

Long-term impacts of childhood neighborhood quality on depression in later midlife mediated by childhood domestic violence: A nationwide longitudinal analysis.

BACKGROUND: Depression affects 264 million people globally, with a high prevalence in China. Adverse childhood experiences, such as poor neighborhood quality and domestic violence, significantly contribute to depression in later midlife. OBJECTIVE: This study aimed to examine the impact of childhood neighborhood quality (CNQ) and childhood domestic violence (CDV) on depression in later midlife and explore the mediating role of domestic violence. PARTICIPANTS AND SETTING: Data from the China Health and Retirement Longitudinal Study (CHARLS), involving 10,139 participants aged 45 and older, we

The mediating role of childhood emotional neglect in the association between childhood neighborhood quality and adult depression outcomes: A nationwide longitudinal analysis.

BACKGROUND: Depression is a prevalent mental health disorder with personal and societal costs. Childhood experiences, including neighborhood quality and emotional neglect, may influence adult depression risk. OBJECTIVE: To examine the relationships between childhood neighborhood quality (CNQ), childhood emotional neglect (CEN), and adult depressive symptoms, and investigate the potential mediating role of CEN. PARTICIPANTS AND SETTING: 15,730 Chinese adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Weighted multiple regression, Karlson-Holm

Atherogenic Index of Plasma mediates the association between Life's Crucial 9 with overactive bladder: a secondary data analysis from NHANES.

BACKGROUND: Some studies suggest a potential link between cardiovascular health, lipid, and overactive bladder (OAB). Life's Crucial 9 (LC9) … is and restricted cubic splines (RCS) were further used to verify their relationship. Additionally, mediation analysis was conducted to explore the potential role of Atherogenic Index of Plasma levels in the association between Life's Crucial 9 and overactive bladder. RESULTS: A total of 25,628 participants were included in this study, among whom 5,150 reported ove …

Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome.

Non-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has a largely unknown genetic basis across ancestries. To our knowledge, this is the first trans-ethnic meta-analysis of genome-wide association studies on SPGF, involving 2255 men with idiopathic SPGF and 3608 controls from European and Asian populations. Using logistic regression and inverse variance methods, we identify two significant genetic associations with Sertoli cell-only (SCO) syndrome, the most extreme SPGF phenotype. The G allele of rs34915133, in the major histocompatibility com

Identification of preventive biomarkers associated with circadian rhythms in traumatic brain injury-mediated depression: Expression of SERPINE1 protein and bioinformatics analysis.

Traumatic brain injury (TBI) represents the leading cause of trauma-related mortality, with depression being the most common psychiatric condition following TBI. Although disruptions in circadian rhythms and clock genes have been linked to both conditions, their precise regulatory mechanisms remain unclear. Identifying circadian rhythm-related genes is critical for the prevention and diagnosis of TBI and depression. This study employs Mendelian Randomization (MR) analysis to establish a positive correlation between TBI and depression. Using Weighted Gene Co-expression Network Analysis (WGCNA)

Effect of lipid-lowering therapies on flow-mediated dilation in patients: A systematic review and meta-analysis of clinical randomized controlled trials.

Numerous lipid-lowering medications are commonly used in clinical settings; however, their impact on vascular endothelial function remains unclear. This study employed techniques like flow-mediated dilation (FMD) to demonstrate the relative effects of lipid-lowering medications on vascular function. PubMed, Embase, and World of Science were searched from January 1, 2011 to October 1, 2024, and the language was limited to English. Randomized controlled trials (RCTs) have assessed the impact of lipid-lowering medications versus placebos on FMD in individuals. The outcomes included FMD, pulse wav

Single-cell multi-omics analysis identifies SPP1+ macrophages as key drivers of ferroptosis-mediated fibrosis in ligamentum flavum hypertrophy.

BACKGROUND: Ligamentum flavum hypertrophy (LFH) is a primary contributor to lumbar spinal stenosis. However, a thorough understanding of the cellular and molecular mechanisms driving LFH fibrotic progression remains incomplete. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed to construct the single-cell map of human ligamentum flavum (LF) samples. An integrated multi-omics approach, encompassing scRNA-seq, bulk RNA sequencing (bulk RNA-seq), and Mendelian randomization (MR), was applied to conduct comprehensive functional analysis. Clinical tissue specimens and animal models wer

Mendelian Randomization Analysis Reveals the Causal Relationships Between Autoimmune Diseases and Idiopathic Thrombocytopenic Purpura and the Mediating Role of Immune Cells.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is related to multiple autoimmune diseases clinically, yet the causal relationship remains unclear. This study employed Mendelian randomization (MR) to explore the genetic causal relationship between autoimmune diseases and ITP and potential mediators in the European population. METHODS: Summary statistics of 10 common autoimmune diseases and ITP were extracted for analysis. Bidirectional two-sample MR and two-step MR were conducted. RESULTS: Multiple sclerosis (MS, inverse variance weighted [IVW]: odds ratio (OR)=5.840E+16, false discove

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… Although it does not reach the traditional statistical significance level, the result still has a certain suggestive effect, indicating a possible association. 19 Mediation Analysis Additionally, we employed a two-step MR study to explore whether the 731 kinds of immune cells mediate the causal routes … Mediator analysis revealed that CD20 on IgD+ CD38+ B cell played a partial mediating role in the causal pathway from CeD to ITP. …

Body Mass Index and Hypertension as Mediators of the Association Between Age at Menarche and Subclinical Atherosclerosis: A Sex-Specific Mendelian Randomization Analysis.

BACKGROUND: Early age at menarche (AAM) has been associated with a higher risk of carotid artery intima-media thickness (cIMT), an indicator of subclinical vascular disease, albeit the mechanisms underlying this association remain elusive. A better understanding of the relationship between AAM, modifiable cardiometabolic risk factors, and subclinical atherosclerosis may contribute to improved primary prevention and cardiovascular disease treatment. We aimed to investigate the putative causal role of AAM on cIMT, and to identify and quantify the potentially mediatory effects of cardiometabolic

Mediators of sex-specific differences in rates of stroke mimics among patients treated with intravenous thrombolysis: A nationwide analysis of 174,995 patients.

INTRODUCTION: Women are at higher risk of stroke mimics; however, the underlying reasons are unclear. METHODS: In this retrospective cohort study of the 2016-2020 National Inpatient Sample database, we identified patients treated with intravenous thrombolysis (IVT). Demographic information, vascular risk factors, comorbidities, and presence of known risk factors for stroke mimics (seizures, migraines, demyelinating diseases, psychiatric illnesses, and functional neurological disorders [FND]) were identified using ICD-10 codes. Rates of no cerebral infarction (NCI) were compared between men an

The role of cerebrospinal fluid metabolites in mediating the impact of lipids on Late-Onset Alzheimer's Disease: a two-step mendelian randomization analysis.

BACKGROUND: Although research has indicated correlations between lipids, cerebrospinal fluid (CSF) metabolites, and Late-Onset Alzheimer's Disease (LOAD), the specific causal relationships among these elements, as well as the roles and mechanisms of the cerebrospinal fluid metabolites, remain unclear. METHODS: Statistical datasets derived from Genome-Wide Association Studies (GWAS) were utilized to assess the bidirectional causal relationships between lipids and LOAD. Subsequently, genetic variants associated with CSF metabolites and established lipids underwent a two-step Mendelian randomiza

Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Advanced combination treatment (ACT), defined as a combination of at least 2 biologic agents, a biologic agent and an oral small molecule, 2 oral small molecules drug with different mechanisms of action is a proposed strategy to improve outcomes in patients with immune-mediated inflammatory disease (IMID). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ACT with monotherapy in patients with select IMIDs. METHODS: Through a systematic literature search, we identified 10 RCTs (n = 1154) comparing ACT with single agent therapy (mono