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461 papers

Comparative Effects of Laparotomy and Laparoscopy-Assisted Embryo Transfer on Oxidative Stress and Thiol-Disulphide Homeostasis in Tuj Ewes.

Demir MC et al. · Jul 1, 2026

Objectives In this study, it was aimed to compare the effects of embryo transfer performed via laparotomy and laparoscopy on thiol-disulphide homeostasis and some oxidative stress markers in Tuj ewes. Methods In the study, 10 Tuj ewes were randomly divided into two groups (laparotomy, n = 5; laparoscopy, n = 5). A progesterone-based synchronization protocol was applied to all animals. Blood samples were collected immediately before surgery, immediately after surgery, and at 24 and 48 h postoperatively. Serum levels of glutathione (GSH), malondialdehyde (MDA), total thiol (TT), native thiol (NT), disulphide (Ds) and thiol-disulphide ratios were determined. Results Group, time, and group × time interactions were found to be statistically significant for GSH, MDA, TT, and NT parameters (p 0.05), time-dependent changes in these parameters were statistically significant (p Conclusions As a result, it was concluded that the surgical approach used in embryo transfer affects the systemic oxidative stress response and that thiol-disulphide homeostasis can be considered a sensitive biomarker for revealing these differences. It was determined that the laparoscopic embryo transfer method disrupts redox balance to a lesser extent and better preserves the antioxidant defence system compared with laparotomy.

Agricultural and Biological Sciences

Drug Use and Social Connectivity Related to Hepatitis C Infection Among Rural People Who Use Drugs.

Rains A et al. · Jul 1, 2026

People who use drugs (PWUD) have a disproportionately elevated risk of hepatitis C virus (HCV). Appropriate screening and treatment may be limited, especially in rural environments experiencing healthcare shortages. In order to develop targeted intervention strategies for rural PWUD, we investigated individual and network-level correlates of HCV positivity. Survey data were collected from PWUD from the Illinois region of the Federal Delta Regional Authority (DRA). The primary outcome of interest was HCV positivity by self-report. We explored associations between HCV positivity and individual demographic, drug use, and service utilisation characteristics as well as degree of connectedness within social networks. Three hundred and two participants were included in analyses. At the individual level, HCV positivity was associated with injection drug use, overdose history, and prior receipt of substance use treatment. Two hundred and one participants had at least one connection to a peer via referral chains, most of which contained a mix of HCV-negative and positive individuals. Of note, isolated individuals had comparable rates of HCV positivity compared to their socially connected peers. Degree of connectedness was not associated with HCV positivity. This study highlights the heterogeneity, both with respect to HCV positivity and other characteristics, among networks of rural PWUD. Given that most participants were connected to others, HCV interventions led by peer champions may facilitate improved access to critical services for risk mitigation.

Medicine

Paternal perinatal mental health and early child development: An outcome-wide analysis.

Scarlett H et al. · Jul 1, 2026

Paternal mental health (PMH) has been shown to associate with child development as early as infancy. However, the moderating effects of certain contextual factors remain poorly understood. Using data from the French SEPAGES cohort, an outcome-wide analytic approach was used to investigate the relationship between PMH during pregnancy (n = 166), 0-12 months postnatally (n = 117), and 12-24 months postnatally (n = 207) with child socioemotional, behavioral and cognitive outcomes at two and three years. Mother's mental health, child sex and parent's professional class were then tested as potential moderators. Findings revealed no significant associations between paternal depression or anxiety with any measure of child development. However, mother's professional class and maternal prenatal depression moderated the association between paternal anxiety and several areas of child development, with children of lower maternal professional classes showing poorer cognitive outcomes but improved social perception when exposed to paternal anxiety. Children exposed to paternal anxiety showed worse working memory outcomes and future-oriented tasks and organization when also exposed to maternal depression. While our findings contrast with current research, showing no relationship between PMH and child development, they highlight the importance of considering family socioeconomic position when studying the relationship between PMH and child development.

Medicine

Interaction Between Rec8 and Mis4 Is Required for Axis-Loop Chromatin Formation and Homologous Chromosome Recombination During Meiosis.

Sakuno T et al. · Jul 1, 2026

The Rec8 cohesin complex is required for the pairing and recombination of homologous chromosomes during meiosis, as well as for the cohesion of sister chromatids. In the fission yeast Schizosaccharomyces pombe, we previously identified a rec8-F204S mutant that lost the ability to assemble the axis-loop chromatin structure without losing sister chromatid cohesion. This mutant showed reduced meiotic recombination, indicating that pairing and recombination of homologous chromosomes require the formation of the axis-loop chromatin structure mediated by the Rec8 cohesin complex. Loading of the Rec8 cohesin complex onto chromatin is mediated by Mis4 (NIPBL in humans; Scc2 in yeast). In this study, to elucidate the functions of Mis4, we identified a mis4-LR mutant (L1150S and R1159G) that reproduced the phenotypes of the rec8-F204S mutant, which is defective in chromatin axis formation and homologous recombination while retaining sister chromatid cohesion. These mutation sites (Mis4-L1150, Mis4-R1159, and Rec8-F204) are all localized at the interaction surface between Mis4 and Rec8. Biochemical analysis revealed that the Mis4-LR mutant protein exhibited reduced Rec8-binding activity. Considering that the mis4-LR mutant phenocopied the rec8-F204S mutant, our results demonstrate that the Mis4-Rec8 interaction is required for proper formation of Rec8-dependent meiotic chromosome axis.

Biochemistry, Genetics and Molecular Biology

A Roadmap for Using Hybridisation Capture-Based Target Enrichment of Ancient Environmental DNA in Palaeoecology.

Foster NR et al. · Jul 1, 2026

Recovering ancient DNA from environmental samples is transforming the way we understand historical ecosystems. While high-throughput sequencing of the total DNA in environmental samples (shotgun metagenomic sequencing) reveals the taxonomic contents of these samples, the genetic signals of some taxa (e.g., eukaryotes) can be weak compared to the background levels of DNA from organisms such as bacteria, requiring deep sequencing approaches that are costly. Thus, to increase cost-effectiveness, pre-sequencing enrichment of target DNA can be advantageous. One technique to enrich this target DNA is hybridisation capture, where short RNA or DNA baits are designed to match, bind and isolate specific stretches of DNA. Hybridisation capture has previously been applied to recover DNA from ancient skeletal remains, but it is only beginning to emerge as an approach to characterise organisms from ancient environmental samples. Thus, there is limited information on establishing hybridisation capture workflows for ancient environmental DNA applications, including the limitations and advantages. This mini review focuses on establishing a roadmap for the applications of hybridisation capture to ancient environmental DNA samples.

Biochemistry, Genetics and Molecular Biology

Validation of Risk Models for Predicting Post-SVR HCC in Real-World Surveillance Across Global Geographic Regions.

Toyoda H et al. · Jul 1, 2026

Background & aims Several clinical risk models have been proposed to stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis C virus (HCV) after sustained virologic response (SVR). However, validation efforts have focused on monocentric or country-specific cohorts, and it is unclear if clinical risk models can be broadly applied to global populations. We characterised regional variation in model performance for HCC risk stratification in post-SVR patients. Methods Four HCC clinical risk models (aMAP score, FIB-4 index, GES score, and Toronto HCC risk index [THRI]) were analysed in six real-world cohorts, which included 8796 post-SVR patients from different geographic regions globally. Model discrimination was assessed using Harrel's c-statistic index. HCC incidence rates were compared across low-, intermediate-, and high-risk groups for each model. Results Distributions of patient characteristics and HCC incidence rates varied across geographic regions. Predictive performances of models were comparable within each cohort despite the model with the highest c-statistics differing by regions. Performance was lower than those from original reports overall; c-statistics of models across most regions remained below 0.70. Conclusions There remains a continued need to improve discrimination and calibration of clinical models to stratify HCC risk in post-SVR patients. Accuracy of models may differ by geographic region, underscoring the importance of external validation to assess transportability of models and suggesting no single model can be universally applied.

Medicine

Effects of a 4-Week Multi-Exercise Isometric Resistance Training Programme on Resting and Ambulatory Blood Pressure in Normotensive Adults.

Wright BH et al. · Jul 1, 2026

Isometric resistance training (IRT) can reduce resting and ambulatory blood pressure (AmBP) yet established exercise methods lack versatility and may present with participation barriers. An isometric training band (ITB) has been identified as an alternative modality; however, its long-term effects on resting and ambulatory blood pressure (BP) remains unknown. This study assessed the effects of the ITB on resting BP and AmBP following 4 weeks of IRT. Forty-two normotensive adults (22 male, 20 female; mean ± SD, age 31 ± 14 years, systolic [sBP], 120 ± 5 mmHg, diastolic [dBP], 72 ± 7 mmHg), were randomised to a control (CON), isometric handgrip (IHG) or ITB group. Resting (systolic, diastolic, mean arterial BP and heart rate [HR]) and AmBP (24-h, daytime and night-time) were measured pre- and post-4 weeks of supervised IRT (4 x 2-min contractions at 30% MVC [IHG] or 4 x 2-min contractions at CR-10 values equivalent to 30% MVC [ITB]). Resting sBP was reduced for IHG (-4.6 mmHg, p 0.05 across all measures). These findings suggest 4 weeks of IRT using the ITB can elicit reductions in resting BP and night-time AmBP in normotensives comparable to IHG, indicating the ITB may offer a practical and cost-effective alternative to established interventions.

Medicine

The T Cell Receptor: Molecular Sensor, Therapeutic Mediator and Probabilistic Driver of Adaptive Immunity.

Schober K. · Jul 1, 2026

Advances in high-throughput sequencing, single-cell profiling, and genome engineering have transformed the study of T cell receptors (TCRs), enabling the identification and functional interrogation of antigen-specific repertoires at an unprecedented scale. This review discusses how recent methodological developments-including high-dimensional TCR discovery strategies, physiological receptor engineering, and longitudinal in vivo analyses-have reshaped our understanding of TCR-driven immune responses. Recruitment into immune responses originates from diverse naïve precursor pools and results in polyclonal populations in which multiple clonotypes contribute to antigen recognition. Within such populations, receptor properties, such as TCR avidity, influence the likelihood of recruitment, expansion, and persistence. However, the impact of these parameters depends strongly on biological context, including antigen availability, cellular competition, and tissue environment. Physiological engineering approaches, such as orthotopic TCR replacement, now enable causal interrogation of receptor function while preserving endogenous regulatory control. Together with advances in spatial and longitudinal profiling of human immune responses, these approaches allow increasingly precise analyses of connections between TCR identity and T cell fate. Integrating insights across antigen discovery, receptor engineering, and in vivo dynamics suggests that TCR biology is shaped by the interplay of receptor sequence, regulatory context, and tissue environment across time. Understanding these relationships will be essential for interpreting immune responses and for guiding the rational design of T cell-based immunotherapies.

Medicine

Preliminary Outcomes of a Brief Values-Guided Self-Management Intervention to Improve Glucose Levels Among Emerging Adults With Type 1 Diabetes and Above-Recommended HbA1c: A Pilot Study.

Styles SE et al. · Jul 1, 2026

Introduction A minority of young adults with type 1 diabetes achieve > 70% time in range (TIR; 70-180 mg/dL [3.9-10 mmol/L]), as recommended. Self-management goals based on self-chosen values (whatever is most important to an individual) may motivate engagement in self-management tasks that could improve TIR. This study explored the acceptability, feasibility, and potential outcomes of values-guided self-management. Methods A single-arm quasi-experimental pilot study was conducted with 14 participants aged 18-25 years and HbA 1c ≥ 58 mmol/mol (7.5%). The intervention consisted of a single 1:1 session ( Results Fourteen participants received the intervention. The intervention was acceptable and feasible to implement. The mean change (95% CI) between pre- and post-intervention TIR was an increase of 2.2 (-1.2, 5.7) percentage points, mostly through a decrease in time above range. The standardized mean change (95% CI) in progress towards valued living was 0.72 (0.27, 1.16) with small improvements in diabetes-specific acceptance and carrying out valued actions. Conclusions A brief values-guided self-management intervention shows promise to improve time in range among emerging adults with type 1 diabetes and above recommended HbA 1c . Further investigation of values-guided self-management is warranted. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12620000200987; https://www.anzctr.org.au/ACTRN12620000200987.aspx).

Medicine

Serum Advanced Glycation End Products as Drivers of Poor Tendon Outcomes in Diabetes? An Emerging Hypothesis and Narrative Review.

Gutierrez EJ et al. · Jul 1, 2026

Introduction Tendon injuries in individuals with diabetes are difficult to reverse, and the mechanisms driving poor healing, extracellular matrix disruption, and altered biomechanics remain poorly understood. Many individuals with prediabetes or diabetes are also overweight or obese, and increased visceral adiposity alters adipokine levels and promotes chronic inflammation. While multiple factors influence tendon healing and extracellular matrix (ECM) remodelling, we suggest that circulating advanced glycation end-products (AGEs) may drive delayed healing, collagen disorganization, and compromised biomechanical properties in diabetes. Methods A comprehensive narrative review of the literature was conducted using PubMed and Embase to synthesize current and emerging evidence on the relationship between AGEs, tendon properties, and tendon healing in diabetes. Experimental, translational, and clinical studies, as well as relevant review articles involving cell, animal, and human models, were critically analysed. Results This narrative review explores the limited evidence linking serum AGE accumulation and Receptor for Advanced Glycation End-Product (RAGE) activation to tendon pathology and poor healing. Traditionally, tendon dysfunction in diabetes has been attributed to non-enzymatic collagen crosslinking. However, there is mixed evidence demonstrating increased tendon AGE content or stiffness in diabetic patients compared to age-matched controls, suggesting alternative mechanisms. Therefore, we outline recent in vitro, animal, and human studies on AGE and RAGE in tendons and propose future directions. Conclusion We propose that a systemic rise in serum AGEs impairs tendon healing by activating RAGE and disrupting cellular pathways required for repair. Future studies investigating the role of AGEs and other circulating factors may provide insights into the high incidence of tendon injuries and impaired healing in individuals with diabetes and related metabolic disorders.

Medicine