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Objective: The purpose of this systematic review and meta-analysis is to assess the association of handgrip strength (HGS) in subjects with high-normal or mildly elevated and low-normal serum uric acid (SUA) reported by quartiles.

Methods: The research protocol was registered at PROSPERO (CRD420251050351). We searched four databases to obtain relevant articles reporting HGS by SUA quartiles in subjects without gout. Outcomes were compared by combining the third and fourth SUA (higher) quartiles versus the first and second (low) quartiles. The risk of bias was assessed using the Newcastle‒Ottawa Scale, and heterogeneity with the I² test. The results are reported as the mean difference (MD), standardized MD (SMD), or odds ratio (OR).

Results: Seven cross-sectional studies, including 18,765 adult subjects with higher SUA quartiles showed significant higher HGS (SMD: 0.21, 95% confidence interval [CI]: 0.03, 0.39), body mass index (MD: 1.02 kg/m², 95% CI: 0.48, 1.55), total cholesterol (SMD: 0.14, 95% CI: 0.05, 0.24), LDL-cholesterol SMD: 0.13, 95% CI: 0.09, 0.17), and triglycerides (SMD: 0.26, 95% CI: 0.11, 0.41) than those with lower SUA quartiles. HDL-cholesterol was significantly reduced in subjects with higher SUA (SMD: -0.13, 95% CI: -0.20, -0.07). High SUA levels were associated with a drinking history (OR: 1.21, 95% CI: 1.10, 1.34) and hypertension (OR: 1.51, 95% CI: 1.15, 1.99).

Conclusions: Subjects with higher normal SUA levels showed higher HGS compared to those with lower normal levels.

Progress toward Universal Health Coverage (UHC) remains a priority for low- and middle-income countries (LMICs). For countries that have adopted Social Health Insurance (SHI) as a strategy, expanding coverage among informal sector households presents an important pathway to this goal. This scoping review examines strategies and interventions employed in LMICs to improve the enrollment and retention of informal sector households in SHI schemes. The review highlights common barriers, including irregular incomes, limited awareness, administrative challenges, and trust deficits. Potential strategies include designing flexible contribution mechanisms, simplified registration processes, targeted awareness campaigns, leveraging existing community structures, and designing comprehensive benefit packages that balance coverage goals with fiscal sustainability. Our findings emphasize the importance of context-specific and innovative approaches that could include tiered premiums, mobile payment platforms, and partnerships with microfinance institutions to address financial and logistical barriers. However, there is also evidence to suggest that net revenue gains from contributory mechanisms are typically modest, with enrollment expansion often requiring substantial public subsidies and incurring additional administrative costs. For Zambia, integrating some of these lessons into the National Health Insurance Scheme (NHIS) offers a pathway to enhancing coverage among the informal sector and advancing equitable access to healthcare, while acknowledging the fiscal constraints.

Alterations in the gut microbiota, known as gut dysbiosis, are associated with inflammatory bowel disease (IBD). There is a need for model systems that can recapitulate the IBD gut microbiome to better understand the mechanistic impact of differences in microbiota composition and its functional consequences in a controlled laboratory setting. To this end, we introduced fecal samples from patients with Crohn's disease (CD) and ulcerative colitis (UC), as well as from healthy control subjects, to miniature bioreactor arrays (MBRAs) and analyzed the microbial communities over time. We then performed two functional assessments. First, we evaluated the colitogenic potential of the CD microbiotas in genetically susceptible germ-free IL-10-deficient mice and found that colitogenic capacity was preserved in a bioreactor-cultivated CD microbiota. Second, we tested impaired colonization resistance against Clostridioides difficile in UC microbiotas using the MBRA system and found that UC microbiotas were innately susceptible to C. difficile colonization while healthy microbiotas were resistant, consistent with what is seen clinically. Overall, our results demonstrate that IBD microbiotas perform comparably to healthy donor microbiotas in the MBRA system, successfully recapitulating microbial structure while preserving IBD-specific functional characteristics. These findings establish a foundation for further mechanistic research into the IBD microbiota using MBRAs.

Background: Premature ovarian insufficiency (POI) significantly impairs female fertility and poses substantial health risks; however, its pathogenesis is incompletely understood, and effective therapeutic interventions are limited. Although gut bacteriome has been closely associated with ovarian dysfunction, the role and therapeutic potential of gut viruses, which far outnumber bacteria, remain largely unexplored.

Results: Therefore, we recruited 60 healthy reproductive-aged women and recently diagnosed POI patients and investigated these concerns using various techniques, including whole-genome shotgun sequencing of virus-like particle (VLP) and fecal virome transplantation (FVT) in CTX-induced POI rats. We found considerable interindividual variability in the gut virome. The virome of POI patients exhibited significant dysbiosis, characterized by a marked reduction in virulent phage, significant changes in predominant phages, and a notable increase in horizontal gene transfer of resistance genes and virulence factors. Furthermore, gut VLPs from the healthy reproductive-aged women significantly improved the condition of POI rats. Conversely, gut VLPs from POI patients markedly impaired the ovarian function and reproductive capacity of healthy rats. The above regulatory effect is primarily due to modulations of gut bacteriome, specifically the estrobolome, and intestinal barrier integrity, which subsequently affect hypothalamic-pituitary-ovarian axis hormone levels and regulate ovarian oxidative stress and inflammation, thereby influencing ovarian function.

Conclusions: Our findings demonstrate the critical roles of the gut virome in regulating ovarian function and provide new insights into the pathogenesis of POI. This study also underscores the therapeutic potential of the gut virome in improving ovarian dysfunction and female infertility including POI.

Nanobodies have emerged as promising tools for many biotechnological applications due to their small size, high stability and remarkable binding specificity. Next-Generation Sequencing (NGS) enables deep profiling of large nanobody libraries and panning campaigns; however, the scale and diversity of nanobody NGS datasets presents a significant bioinformatic challenge. To this end, we have developed alpseq, an optimized, open-source software pipeline designed specifically for the efficient and accurate processing of NGS data from nanobody libraries and panning campaigns. alpseq is also paired with a PCR-free sequencing library preparation protocol to allow researchers to easily generate their own data while avoiding biases. The alpseq software pipeline is composed of two parts: a pre-processing module written in Nextflow efficiently handles raw nanobody reads in a single line of code. These results are then fed into the analysis module, which contains a comprehensive suite of functions for quality control, diversity analysis, identification of enriched sequences and clustering. alpseq also creates a user-friendly interactive report which empowers scientists to explore their data without the need for extensive bioinformatic experience. Sophisticated panning campaign designs are supported, such as replicates and comparisons between different pans to find cross-binding leads. alpseq thus generates insights into the nanobody selection process and delivers a list of lead candidates for further experimental validation and downstream applications. alspeq is available at https://github.com/kzeglinski/alpseq.

The current clinical classification of coronavirus disease 2019 (COVID-19) does not adequately capture the biological heterogeneity observed among patients. To address this gap, the present study aimed to identify distinct subtypes of severe COVID-19 through unsupervised clustering analysis. We analyzed nine publicly available RNA sequencing datasets of peripheral blood samples from the GEO database. After identifying differentially expressed genes (DEGs), we applied a consensus clustering algorithm to classify the samples into distinct subtypes. To further characterize these subtypes, we performed gene set enrichment analysis and assessed immune cell infiltration to understand their underlying biological mechanisms. Based on the 139 upregulated DEGs of severe COVID-19 infection, patients were divided into subtype A, subtype B, and subtype C, each with different molecular and cellular characteristics. Subtype A was characterized by activated neutrophils that undergo degranulation and respond to bacteria or fungi. Subtype B showed significant activation in canonical pathways associated with interferon-alpha/beta signaling. Subtype C was characterized by immune cell activation associated with pathways of mitotic and cell cycle. These results facilitate the development of a precise classification framework, which informs the design of molecular diagnosis and provides actionable guidelines for stratified therapy in severe COVID-19 infection in the future.

Antibody-drug conjugates (ADCs) and other biopharmaceuticals require robust analytical methods to assess biotransformation in biological matrices. Current approaches often require off-line enrichment and extensive chromatographic separation, limiting throughput and complicating data processing. We developed a native affinity liquid chromatography-mass spectrometry (aLC-MS) method using POROS CaptureSelect FcXL columns combined with optimized solvents and MS parameters for direct analysis (1D aLC-MS) of ADCs and other antibody-derived formats in complex sample matrices, such as serum. The method was evaluated using stability studies and concentration series in mouse serum. Direct analysis enabled accurate determination of drug-antibody ratio (DAR), drug-load distribution (DLD) and relative drug abundance across samples without chromatographic peak integration. Stability studies revealed distinct ADC biotransformation profiles in serum versus PBS, including maleimide hydrolysis and disulfide exchange at under-conjugated cysteine sites. The aLC-MS method achieved excellent linearity (R² = 0.99) over 125-2000 µg/mL in serum and demonstrated sensitivity to 31.25 µg/mL. This rapid, selective aLC-MS method enables high-throughput monitoring of ADC quality attributes in complex matrices with minimal sample preparation, supporting biopharmaceutical product development and bioanalysis applications. The method is exclusively based on MS results, which makes data processing and reporting fast and easy to automate.

Autoimmune gastritis (AIG) is an autoimmune disease characterized primarily by the destruction of gastric parietal cell structure and atrophy of the gastric fundic and body mucosa. The global prevalence of AIG is approximately 3.85%. Its main complications include pernicious anemia, gastric neuroendocrine tumors, and gastric cancer, which pose significant health risks. Currently, targeted treatment options for AIG are lacking worldwide. Animal models of AIG are crucial for investigating its pathogenesis and for developing drug therapies. However, reproducible methods for establishing AIG animal models remain scarce. This article provides a systematic review of internationally employed methods for modeling AIG in animals. These methods are categorized and discussed based on the modeling approaches and mechanisms, including neonatal thymectomy, genetically modified animals such as TxA23 and Ctox mice, inducer-based methods such as H⁺/K⁺-ATPase immunization, viral infection, and combined modeling strategies. In addition, the types of modeling agents and the time required for model establishment are also examined. This review highlights existing challenges, such as the lack of uniform modeling standards and evaluation criteria, and aims to provide a foundation for further exploration of AIG.

Although numerous drugs have been developed for intravaginal administration, the implementation of personalized intravaginal treatment options is limited. The MedRing overactive bladder (OAB) system is a medical device for intravaginal oxybutynin administration via patient-controlled schedules. The primary aim was to assess the feasibility, tolerability, and safety of intravaginal oxybutynin administration via the MedRing OAB system. Second, the functioning of the MedRing OAB system, user satisfaction and quality of life (QoL) were assessed. Female OAB patients were included to receive the MedRing OAB system. Treatment was divided into three periods with increasing dosing flexibility: 2 mg at three fixed timepoints daily, 2 mg at three patient-defined timepoints daily, and flexible dosing up to 6 mg/day of 1 or 2 mg doses. Feasibility, tolerability, satisfaction, and QoL were assessed via questionnaires, safety via treatment-emergent adverse events (TEAEs), device deficiencies (DDs) and physical examination and functioning via pharmacokinetics and MedRing logs. Thirteen patients were enrolled, of whom three patients discontinued the study prematurely. Most patients reported low user burden, found the system practical and expressed positive opinions. The TEAEs were consistent with known oxybutynin effects and local TEAEs were comparable to other intravaginal devices. Most DDs were synchronization difficulties, which improved after a software update. After 10 minutes, oxybutynin levels were detected in 12 of the 13 patients. This study showed that the MedRing OAB system appears to be a feasible, tolerable and safe alternative intravaginal oxybutynin administration for 28 days in OAB patients, offering a potential alternative to existing treatment options and introducing personalized patient care.