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Abstract Niches are specialized tissue microenvironments that control stem cells functioning. The bone marrow mesenchymal stem cell niche defines a location within the marrow in which mesenchymal stem cells are retained and produce new cells throughout life. Deciphering the signaling mechanisms by which the niche regulates stem cell fate will facilitate the use of these cells for therapy. Recent studies, by using state‐of‐the‐art methodologies, including sophisticated in vivo inducible genetic techniques, such as lineage‐tracing Cre/loxP mediated systems, in combination with pharmacological inhibition, provide evidence that sensory neuron is an important component of the bone marrow mesenchymal stem cell niche. Strikingly, knockout of a specific receptor in sensory neurons blocked stem cell function in the bone marrow. The knowledge arising from these discoveries will be crucial for stem cell manipulation in the future. Here, we review recent progress in our understanding of sensory nerves biology in the stem cell niche.

A suitable pairwise relatedness estimation is key to genetic studies. Several methods are proposed to compute relatedness in autopolyploids based on molecular data. However, unlike diploids, autopolyploids still need further studies considering scenarios with many linked molecular markers with known dosage. In this study, we provide guidelines for plant geneticists and breeders to access trustworthy pairwise relatedness estimates. To this end, we simulated populations considering different ploidy levels, meiotic pairings patterns, number of loci and alleles, and inbreeding levels. Analysis were performed to access the accuracy of distinct methods and to demonstrate the usefulness of molecular marker in practical situations. Overall, our results suggest that at least 100 effective biallelic molecular markers are required to have good pairwise relatedness estimation if methods based on correlation is used. For this number of loci, current methods based on multiallelic markers show lower performance than biallelic ones. To estimate relatedness in cases of inbreeding or close relationships (as parent-offspring, full-sibs, or half-sibs) is more challenging. Methods to estimate pairwise relatedness based on molecular markers, for different ploidy levels or pedigrees were implemented in the AGHmatrix R package.

Genomic selection is an efficient approach to get shorter breeding cycles in recurrent selection programs and greater genetic gains with selection of superior individuals. Despite advances in genotyping techniques, genetic studies for polyploid species have been limited to a rough approximation of studies in diploid species. The major challenge is to distinguish the different types of heterozygotes present in polyploid populations. In this work, we evaluated different genomic prediction models applied to a recurrent selection population of 530 genotypes of Panicum maximum, an autotetraploid forage grass. We also investigated the effect of the allele dosage in the prediction, i.e., considering tetraploid (GS-TD) or diploid (GS-DD) allele dosage. A longitudinal linear mixed model was fitted for each one of the six phenotypic traits, considering different covariance matrices for genetic and residual effects. A total of 41,424 genotyping-by-sequencing markers were obtained using 96-plex and Pst1 restriction enzyme, and quantitative genotype calling was performed. Six predictive models were generalized to tetraploid species and predictive ability was estimated by a replicated fivefold cross-validation process. GS-TD and GS-DD models were performed considering 1,223 informative markers. Overall, GS-TD data yielded higher predictive abilities than with GS-DD data. However, different predictive models had similar predictive ability performance. In this work, we provide bioinformatic and modeling guidelines to consider tetraploid dosage and observed that genomic selection may lead to additional gains in recurrent selection program of P. maximum.

Estimation of allele dosage, using genomic data, in autopolyploids is challenging and current methods often result in the misclassification of genotypes. Some progress has been made when using SNP arrays, but the major challenge is when using next generation sequencing data. Here we compare the use of read depth as continuous parameterization with ploidy parameterizations in the context of genomic selection (GS). Additionally, different sources of information to build relationship matrices were compared. A real breeding population of the autotetraploid species blueberry (Vaccinium corybosum), composed of 1,847 individuals was phenotyped for eight yield and fruit quality traits over two years. Continuous genotypic based models performed as well as the best models. This approach also reduces the computational time and avoids problems associated with misclassification of genotypic classes when assigning dosage in polyploid species. This approach could be very valuable for species with higher ploidy levels or for emerging crops where ploidy is not well understood. To our knowledge, this work constitutes the first study of genomic selection in blueberry. Accuracies are encouraging for application of GS for blueberry breeding. GS could reduce the time for cultivar release by three years, increasing the genetic gain per cycle by 86% on average when compared to phenotypic selection, and 32% when compared with pedigree-based selection. Finally, the genotypic and phenotypic data used in this study are made available for comparative analysis of dosage calling and genomic selection prediction models in the context of autopolyploids.

Background: Inconsistencies in the Female Sexual Function Index (FSFI) factor structure and current research and clinical guidelines highlight the need for continued exploration of its psychometric evidence. Furthermore, only one study has assessed its measurement invariance (MI), while the only FSFI psychometric study conducted in Chile lacks quality and representativity., Aim: Therefore, this study aimed to evaluate the psychometric properties of the FSFI (ie, structural and convergent validity, and reliability) in a Chilean sample of women, while also examining MI across relationship status and age groups., Method: A sample of 2595 sexually active adult women ( M age  = 32.10, SD age  = 10) was derived from a broader Chilean study (Chilean National Sex and Sexuality Study). We used a confirmatory factor analysis to determine its structural validity, sexual satisfaction (SS) dimensions to establish its convergent validity, and Cronbach's alpha and McDonald's omega to assess the reliability of its scores., Outcomes: Measures of goodness-of-fit., Results: Confirmatory factor analysis supported a six-factor structure. Internal consistency indices for all FSFI dimensions ranged from good to excellent. MI was achieved across socio-demographic variables at the factor covariance level. Convergent validity indicated modest-to-moderate effects in satisfaction differences based on relationship status. Among other findings, Chilean women in a relationship had significantly higher satisfaction with their sexual communication and compatibility than those who were single, which is consistent with previous findings. Meanwhile, women at risk of experiencing sexual problems scored significantly lower across all SS dimensions than those not at risk., Clinical Implications: This study provides evidence that the FSFI is a valid, reliable, and invariant tool for the clinical practice in the sexual health of Spanish-speaking Latino Americans, especially that of Chilean women's sexual function (SF) and problems., Strengths & Limitations: This study provided a comprehensive analysis of the FSFI's psychometric validity evidence, demonstrating its reliability and validity across diverse Chilean women while also offering its first assessment of MI and confirming its suitability for clinical and research use in Spanish-speaking Latino women. Conversely, this study's main caveat lies in having a predominantly younger, cisgender, and heterosexual sample., Conclusion: Nevertheless, this study's findings support the FSFI as a valuable research tool for female SF and well-being, particularly within the Chilean population. This study significantly expands the applicability of the FSFI and underscores its MI across sociodemographic factors, as well as its applicability in the Spanish-speaking Latino-American sociodemographic context, particularly the Chilean one., Competing Interests: The authors have no conflicts of interest, competing interests, or relevant financial or non-financial interests to disclose., (The Author(s) 2025. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.)

School-based prevention drug programs in the United States and Brazil are most commonly delivered by law enforcement officers (LEOs). However, limited research has explored challenges involved in the delivery of these interventions specifically related to their implementation by LEOs. We aim to describe the challenges affecting the implementation of school-based drug prevention programs delivered by LEOs. We conducted a qualitative study using 31 semi-structured interviews with LEOs who delivered the Brazilian version of the DARE-Keepin' it REAL program (fifth- and seventh-grade curriculum) and 8 focus groups with 80 students who participated in the program. All data were thematically analyzed. LEOs perceived devaluation from the police corporation, resulting in resource limitations and commanders' resistance to adapting schedules. Relationships with the school community posed additional challenges. Fifth graders seemed generally positive about LEOs' presence while seventh graders showed more negative responses. LEOs' street-level policing experiences influenced their approach to clarifying the consequences of drug use and willingness to share related experiences, even though this content is not part of the program. Therefore, it is crucial to consider alternative approaches to delivering preventive programs in schools, while simultaneously improving the training of LEOs already involved in program implementation to ensure alignment with evidence-based practices., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: Mesenchymal stromal cells (MSCs) can modulate immune responses and suppress inflammation in autoimmune diseases. Although their safety has been established in clinical trials, the efficacy of MSCs is inconsistent due to variability in potency among different preparations and limited specificity in targeting mechanisms driving autoimmune diseases., Methods: We utilized high-dimensional design of experiments methodology to identify factor combinations that modulate gene expression by MSCs to mitigate inflammation. This led to a novel MSC-based cell therapy, HXB-319. Its anti-inflammatory properties were validated in vitro by flow cytometry, RT-PCR, and mass spectrophotometry. To evaluate in vivo efficacy, we treated a diffuse alveolar hemorrhage (DAH) mouse model (C57Bl/6). Seven days post-DAH induction with pristane, mice received either MSCs or HXB-319 (2X106 cells, IP). On day 14, peritoneal lavage fluid (PLF) and lung tissue were collected for flow cytometry, histopathological examination, and mRNA., Results: HXB-319 increased gene expression levels of anti-inflammatory, angiogenic, and anti-fibrotic factors (eg, TSG-6, VEGF, and HGF). KEGG pathway analysis confirmed significant activation of relevant anti-inflammatory, angiogenic, and anti-fibrotic proteins, corroborating RT-PCR results. In the DAH model, HXB-319 significantly reduced lung inflammation and alveolar hemorrhage compared to MSC-treated and untreated DAH mice. HXB-319 treatment also significantly decreased neutrophils, plasmacytoid dendritic cells, and RORγT cells, increased FoxP3+ cells in PLF, and reversed alterations in mRNA encoding IL-6, IL-10, and TSG-6 in lung tissue compared to DAH mice., Conclusion: HXB-319 effectively controls inflammation and prevents tissue damage in pristine-induced DAH, highlighting its therapeutic potential for autoimmune inflammatory diseases., (© The Author(s) 2024. Published by Oxford University Press.)

This study assesses the prevalence and trends of depression in the European population aged 50 years and older between 2004 and 2022 in different geographical regions. We retrieved and pooled data from waves 1,2,4,5,6,7,8, and 9 of the Survey of Health, Ageing and Retirement in Europe (SHARE) conducted between 2004 and 2022. The 12-item EURO-D scale was used as a continuous marker of depression risk. Twenty-eight countries were classified into five geographical regions (Eastern, Western, Southern and Northern Europe, and Israel) as defined by the United Nations. A total of 375 693 observations corresponding to 146 888 participants (weighted mean age 65.8 years [SE=0.2], 54.2% women) were included in the study. In 2022, the overall prevalence of self-reported depression in Europe was 28.3% (95% CI: 27.0-29.7). From 2004 to 2022, the prevalence of self-reported depression in Europe decreased significantly by 5.9% (95% CI= -8.1 to -3.8). In particular, in Southern Europe, the prevalence of depression decreased significantly by 8.8% (95% CI= -12.3 to -5.2). No significant differences were observed in the other geographic regions. These findings highlight the need to develop depression screening and prevention strategies focused on countries with higher prevalence and identified associated factors., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To better establish the value of vaccination against influenza viruses, we estimated vaccine-averted influenza illnesses among young children and older adults in Chile, Guyana, and Paraguay., Methods: We gathered country- and target population-specific data on monthly influenza hospitalizations, vaccine coverage, and vaccine effectiveness from surveillance records and immunization registries during 2013-2018. We applied a static compartmental model to estimate differences in the number influenza-associated respiratory disease events (symptomatic non-hospitalized illnesses, medically attended illnesses, hospitalizations) in the presence and absence of influenza vaccination programs., Results: Between 2013 and 2018, vaccinating 68% of children aged 6-23 months in Chile averted an annual mean of 14,617 non-hospitalized, 9,426 medically attended, and 328 hospitalized influenza illnesses; vaccinating 28% of children aged 6-23 months in Paraguay averted 1,115 non-hospitalized, 719 medically attended, and 25 hospitalized influenza illnesses. Vaccinating 59% of older adults in Chile averted an annual mean of 83,429 non-hospitalized, 37,079 medically attended, and 1,390 hospitalized influenza illnesses; vaccinating 36% of older adults in Paraguay averted an annual mean of 3,932 non-hospitalized, 1,748 medically attended, and 66 hospitalized influenza illnesses. In Guyana, a hypothetical campaign vaccinating 30% of children <5 years could have prevented an annual 1,496 non-hospitalized, 971 medically attended, and 10 hospitalized influenza illnesses. Vaccinating 30% of adults ≥65 years could have prevented 568 non-hospitalized, 257 medically attended, and 10 hospitalized influenza illnesses., Conclusions: Influenza vaccination averted tens of thousands of illnesses and thousands of hospitalizations in Chile and Paraguay; influenza vaccination could have had a proportional benefit in Guyana., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We estimate annual viral influenza-associated mild-to-moderate illness, hospitalizations, and deaths in six South American countries (Argentina, Brazil, Chile, Ecuador, Paraguay, and Uruguay) during the 2015-2019 influenza seasons as a first step in evaluating the full value of influenza vaccination in the subregion., Methods: We applied a multiplier methodology using monthly hospital discharge and vital statistics death records, influenza surveillance data, and population projections to estimate mild-to-moderate influenza-associated illness, hospitalizations, and deaths. We estimated the uncertainty bounds based on the 2.5th and 97.5th of the Monte Carlo simulated distributions for the number of cases and obtained the ranges from the minimum value of the 2.5th percentile and the maximum value of the 97.5th percentile., Results: In selected countries with a total population of 307 million people, the yearly influenza-associated burden of disease ranged between 51 and 78 million mild-to-moderate influenza illnesses, between 323,379 and 490,049 hospitalizations, and between 22,662 and 46,971 deaths during the 2015-2019 influenza seasons., Conclusions: Each year, influenza is associated with millions of illnesses, hundreds of thousands of hospitalizations and tens of thousands of deaths in six South American countries, affecting a significant portion of the population. Such findings can be used to estimate the number of illnesses averted through vaccination programs and the cost-benefit of influenza vaccines., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear., Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD., Results: Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77-48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10-2.63 and odds ratio 1.65, 95% confidence interval 1.27-2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations., Conclusions: Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components, such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin, have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds, such as lipopolysaccharides and muropeptides, can have opposing effects on endocrine control of host metabolism, where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites, such as short-chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol, can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Developing efficient gene regulation tools is essential for optimizing microbial cell factories, but most existing tools only modulate gene expression at the transcriptional level. Regulation at the translational level provides a faster dynamic response, whereas developing a programmable, efficient and multiplexed translational regulation tool remains a challenge. Here, we have developed CRISPRi and CRISPRa systems based on hfCas13X that can regulate gene translation in Bacillus subtilis. First, we constructed a CRISPRi system to regulate gene translation based on catalytically deactivated hfCas13X (dhfCas13X). Second, we designed unique mRNA-crRNA pairs to construct DiCRISPRa (degradation-inhibited CRISPRa) and TsCRISPRa (translation-started CRISPRa) systems, which can activate downstream gene translation by enhancing mRNA stability or initiating mRNA translation. In addition, we found that fusing dhfCas13X with the RNA-binding chaperone BHfq significantly improved the activation efficiency of the DiCRISPRa and TsCRISPRa systems (43.2-fold). Finally, we demonstrated that the constructed CRISPR systems could be used to optimize the metabolic networks of two biotechnologically relevant compounds, riboflavin and 2'-fucosyllactose, increasing their titers by 3- and 1.2-fold, respectively. The CRISPRa and CRISPRi systems developed here provide new tools for the regulation of gene expression at the translation level and offer new ideas for the construction of CRISPRa systems., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Aims: This study aimed to assess the mode of action of fusaric and 9,10-dehydrofusaric acids on cell respiration by measuring the hyphal oxygen consumption rate, and the effects on cell membrane integrity by determining the electrical conductivity of the mycelium., Methods and Results: Bioactivity-directed fractionation of the active culture medium and mycelium organic extracts from the Fusarium lactis strain SME13-2 isolated from Sapium macrocarpum led to the isolation of two known alkylpicolinic acid derivatives: fusaric acid and 9,10-dehydrofusaric acid, along with the known polyketide bikaverin. Fusaric acid and 9,10-dehydrofusaric acid exhibited antioomycete and antifungal activities, significantly inhibiting the radial growth of Phytophthora capsici, Pythium aphanidermatum, Alternaria alternata, and F. oxysporum. Additionally, they induced changes in colony morphology and negative effects on the ultrastructure of their hyphae. To date, the antimicrobial mode of action of fusaric acid and other alkylpicolinic acid derivatives is not thoroughly understood. Therefore, we investigated their effect on cellular respiration by measuring the oxygen consumption rate of the hyphae and their impact on cell membrane integrity by determining the electrical conductivity of the mycelium. Fusaric and 9,10-dehydrofusaric acids inhibited the respiration of the mycelium and altered the permeability of the cell membrane in the tested phytopathogenic microorganisms in a concentration and exposure time-dependent manner, exerting a greater effect on oomycetes. The disruption of cell membrane integrity resulted in the leakage of cytoplasmic electrolytes into the extracellular medium, which, coupled with respiratory inhibition, could lead to cell death., Conclusions: Fusaric and 9,10-dehydrofusaric acids show potential for the development of new fungicides and anti-oomycetes agents., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Aims: Transcatheter tricuspid valve interventions (TTVI) are increasingly used to treat patients with significant tricuspid regurgitation (TR). The evolution of concurrent mitral regurgitation (MR) severity after TTVI is currently unknown and may be pivotal for clinical decision-making. The aim of this study was to assess the evolution of MR after TTVI and to identify predictors of MR worsening and improvement., Methods and Results: This analysis is a substudy of the TriValve Registry, an international registry designed to collect data on TTVI. This substudy included all patients with echocardiographic data on MR evolution and excluded those with a concomitant tricuspid and mitral transcatheter valve intervention or with a history of mitral valve intervention. The co-primary outcomes were MR improvement and worsening at two timepoints: pre-discharge and 2-month follow-up. This analysis included 359 patients with severe TR, mostly (80%) treated with tricuspid transcatheter edge-to-edge repair (T-TEER). MR improvement was found in 106 (29.5%) and 99 (34%) patients, while MR worsening was observed in 34 (9.5%) and 33 (11%) patients at pre-discharge and 2-month follow-up, respectively. Annuloplasty and heterotopic replacement were associated with MR worsening. Independent predictors of MR improvement were: atrial fibrillation, T-TEER, acute procedural success, TR reduction, left ventricular end-diastolic diameter> 60 mm, and beta-blocker therapy. Patients with moderate-to-severe/severe MR following TTVI showed significantly higher death rates., Conclusion: MR degree variation is common after TTVI, with most cases showing improvement. Clinical and procedural characteristics may predict the MR evolution, in particular procedural success and T-TEER play key roles in MR outcomes. TTVI may be beneficial, even in the presence of functional MR., Competing Interests: Conflict of interest: RH has served as a consultant for Abbott Vascular, Abbott Structural, NaviGate, Philips Healthcare, Medtronic, Edwards Lifesciences, and GE Healthcare; has been the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-supported trials, for which she receives no direct industry compensation; has received speaker fees from Boston Scientific and Baylis Medical; and has received non-financial support from 3mensio. HA has received consulting fees from Abbott and Edwards LifeSciences. MA has served as a proctor/consultant for and has received speaker fees from Abbott, Edwards LifeSciences, Boston, Zoll, and Medtronic; and has received institutional grants from Edwards Lifesciences, Abbott, Medtronic, and LSI Solutions. DB has received speaker honoraria and travel support from Abbott Vascular. KC has received honoraria from Abbott. PD has served as a consultant for Abbott Vascular, 4Tech, Neovasc, and InnovHeart; and has received honoraria from Abbott and Edwards Lifesciences. RE-L has received speaker fees from Abbott, Boston, and Edwards Lifesciences. JH has received speaker honoraria from Abbott Vascular and Edwards Lifesciences. DH has served as proctor for Edwards Lifesciences and Abbott Vascular. DK has received personal fees from Abbott Medical, Edwards Lifescienes, Medtronic Inc., and Pi-Cardio Ltd. outside the submitted work. MA has been a consultant to Abbott Structural Heart and Medtronic. AL has served on the advisory board for Medtronic, Abbott Vascular Boston Scientific, Edwards Lifesciences, Shifamed, NeoChord Inc., V-dyne, and Philips. EL has received grant support and lecture fees from Abbott; and has received lecture fees from Edwards Lifesciences. SL has received travel compensation from Edwards LifeSciences, advisory fees from Bayer, speaker honoraria from Abbott and serves as consultant for New Valve Technology. PL has received speaker fees from Abbott. FP has received travel expenses from Edwards Lifesciences, Abbott Vascular, and Polares Medical. JR-C has received institutional research grants from Edwards Lifesciences. JS has served as a consultant for Edwards Lifesciences. HS has received study honoraria, travel expenses, and consulting fees from 4Tech Cardio, Abbott, Ablative Solutions, Ancora Heart, Bavaria Medizin Technologie, Bioventrix, Boston Scientific, Carag, Cardiac Dimensions, Celonova, Comed BV, Contego, CVRx, Edwards Lifesciences, Endologix, Hemoteq, Lifetech, Maquet Getinge Group, Medtronic, Mitralign, Nuomao Medtech, Occlutech, PFM Medical, ReCor, Renal Guard, Rox Medical, Terumo, Vascular Dynamics, and Vivasure Medical. GT has served as a consultant, physician advisory board member, and faculty trainer for Abbott Structural Heart; has served as a consultant for Medtronic and NeoChord; and has served as a physician advisory board member for JenaValve. K-PK has been a consultant to Edwards Lifesciences. MM has received the following personal fees of minimal amounts since January 2021: from Amgen, Liva Nova, and Vifor pharma as a member of Executive or Data Monitoring Committees of sponsored clinical trials; and from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics for participation to advisory boards and/or speeches at sponsored meetings. PL has been a consultant to Abbott Structural Heart, Edwards Lifesciences, and Medtronic. RSVB has performed unpaid trial activities for Abbott, Edwards Lifesciences, Medtronic, and the University of Göttingen (IIT) and serves as an advisory board or Speakers Bureau member for Abbott Cardiovascular, Edwards Lifesciences, Medtronic, and NeoChord. JW is a consultant for Edwards Lifesciences Inc. SW reports research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. SW serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. ML has received institutional clinical research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. RH has served as a consultant for Abbott Vascular, Abbott Structural, NaviGate, Philips Healthcare, Medtronic, Edwards Lifesciences, and GE Healthcare; has been the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-supported trials, for which she receives no direct industry compensation; has received speaker fees from Boston Scientific and Baylis Medical; and has received nonfinancial support from 3mensio. FM has served as a consultant for and received consulting fees and honoraria from Abbott Vascular, Edwards Lifesciences, Cardiovalve, SwissVortex, Perifect, Xeltis, Transseptal Solutions, Magenta, Valtech, and Medtronic; has reported being a cofounder of 4Tech; has received research grant support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, and Terumo; has received royalties and owns intellectual property rights from Edwards Lifesciences (FMR surgical annuloplasty); and has reported being a shareholder in Cardiovalve, Swiss Vortex, Magenta, Transseptal Solutions, Occlufit, 4Tech, and Perifect. FDM is a consultant and has provided paid expert testimony for Abbott and Boston Scientific. MT has served as a consultant for Abbott Vascular, Boston Scientific, 4Tech, and CoreMedic and has received speaker honoraria from Edwards Lifesciences. SL has received travel compensation from Edwards Lifesciences. GP declares honorarium as speaker and/or institutional research grant from GE Healthcare, Bracco, Heartflow, Menarini, Novartis, Alexion, Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The International Index of Erectile Function (IIEF) stands out for its utility and widespread use to measure sexual function in men. However, it lacks consistency in its internal latent structure across studies, has not been evaluated for measurement invariance, and has not undergone psychometric validation for its 15-item form in Spanish among South American countries., Aim: To examine the IIEF's psychometric evidence (ie, structural/criterion validity and reliability) in a sample of adult men and determine its measurement invariance across relationship status (single vs in a relationship) and age generations (generations Z, Y/millennials, and X)., Methods: A sample of 650 sexually active males was derived from a broader Chilean study (Chilean Sex and Sexuality Study). We used a confirmatory factor analysis to determine the IIEF's structural validity, sexual satisfaction dimensions to establish its criterion-related validity, and Cronbach alpha and McDonald omega to assess the reliability of its scores., Outcomes: Measures of goodness of fit., Results: The evidence supported the 5-factor latent solution. Meanwhile, criterion-related validity revealed subtle yet significant differences in sexual satisfaction, with younger men displaying higher satisfaction in various sexual domains. In contrast, middle-aged men and those in a relationship showed better sexual function. Finally, the IIEF was invariant across age groups and relationship status at the factor covariance level., Clinical Translation: This study provides evidence that the IIEF is a valid, reliable, and invariant tool for the clinical practice in men's sexual health, particularly that associated with their sexual function and dysfunction., Strengths and Limitations: The study included a comprehensive validity analysis of the IIEF's psychometric properties, demonstrating its reliability and validity across diverse Chilean male subpopulations. The study also offered the IIEF's first assessment of measurement invariance and confirmed its suitability for clinical and research use in the Chilean population. Meanwhile, the study's limitations include a lack of clinical population and a sample predominantly younger, cisgender, and heterosexual., Conclusion: Our study provides evidence of the IIEF's 5-factor structure and measurement invariance across age generations and relationship status in Chilean men, supporting its validity for clinical use and research and broadening its applicability in global sexual health studies, particularly in the Spanish-speaking South American male population., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.)

Paracoccidioides are dimorphic fungal pathogens and the etiological agents of paracoccidioidomycosis (PCM). This severe systemic mycosis is restricted to Latin America, where it has been historically endemic. Currently, PCM presents the fewest diagnostic tools available when compared to other endemic mycoses. The main PCM diagnostic methods also have limitations. Molecular methods using different protocols have been proposed, but are restricted to a few regions. An analytical transversal study was conducted to evaluate a new molecular tool using specimens from patients diagnosed with PCM at a reference center for endemic mycoses in Rio de Janeiro, Brazil. After whole nucleic acid (WNA) extraction, RT-qPCR was performed in two independent simplex reactions, targeting the mitochondrial small subunit ribosomal RNA genes of Paracoccidioides brasiliensis and Paracoccidioides lutzii. Additionally, WNAs from all PCM-related Paracoccidioides species and from 114 other fungal strains, as well as from samples obtained from patients diagnosed with other endemic mycoses and tuberculosis, were also tested for specificity. The RT-qPCR targeting P. brasiliensis successfully amplified genetic material from all tested Paracoccidioides species but not P. lutzii, which is why a specific RT-qPCR was designed. The RT-qPCR efficiency was 1.95 (95%) with 100% analytical specificity for both targets. All included PCM clinical samples were positive (100% sensitivity) for P. brasiliensis, and all yielded negative for P. lutzii. Additionally, all samples collected from patients with other diseases were negative, reinforcing the assay's specificity. In conclusion, this study proposes a new accurate tool to cover gaps, contributing to the molecular diagnosis of this neglected disease., (© The Author(s) 2025. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Mucocutaneous Behçet disease often presents a therapeutic challenge. Roflumilast has shown promise in the treatment of other inflammatory dermatological conditions., Objectives: The objective of this study was to evaluate the characteristics, effectiveness and safety of roflumilast in the treatment of Behçet disease-associated aphthosis in routine clinical practice., Methods: We performed a single-cohort ambispective observational study. Eleven patients with Behçet disease treated with roflumilast participated. Data collection included demographic, clinical and outcome variables. Statistical analysis compared 12 weeks of treatment with roflumilast with a previous period without treatment and with a period when the previous treatment was used., Results: During treatment with roflumilast, a reduction in flare-ups and oral ulcers was observed compared with the untreated period and the previous treatment period. A reduction in genital ulcers, pain and ulcer duration was observed between the without treatment period and the roflumilast treatment period. Adverse effects occurred in 54% of patients, most of which were self-limiting or manageable with dose adjustment. No patients withdrew treatment., Conclusions: Roflumilast appears to be a potential option in the treatment of Behçet disease with favourable effectiveness, safety and tolerability profiles. Although further research is needed, roflumilast offers a promising treatment option for Behçet disease-associated aphthosis, which could improve the patients' quality of life and address unmet therapeutic needs., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Trait diversification is often driven by underlying performance tradeoffs in the context of different selective pressures. Evolutionary changes in task specialization may influence how species respond to tradeoffs and alter diversification. We conducted this study to investigate the functional morphology, evolutionary history, and tempo and mode of evolution of the Hymenoptera stinger using Ectatomminae ants as a model clade. We hypothesized that a performance tradeoff surface underlies the diversity of stinger morphology and that shifts between predatory and omnivorous diets mediate the diversification dynamics of the trait. Shape variation was characterized by X-ray microtomography, and the correlation between shape and average values of von Mises stress, as a measure of yield failure criteria under loading conditions typical of puncture scenarios, was determined using finite element analysis. We observed that stinger elongation underlies most of the shape variation but found no evidence of biomechanical tradeoffs in the performance characteristics measured. In addition, omnivores have increased phenotypic shifts and accelerated evolution in performance metrics, suggesting the evolution of dietary flexibility releases selection pressure on a specific function, resulting in a greater phenotypic evolutionary rate. These results increase our understanding of the biomechanical basis of stinger shape, indicate that shape diversity is not the outcome of simple biomechanical optimization, and reveal connections between diet and trait diversification., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE).)

Peto's paradox, which highlights the lower-than-expected cancer rates in larger and/or longer-lived species, is a cornerstone of discussions at the intersection of ecology, evolution, and cancer research. It prompts investigations into how species with traits that theoretically increase cancer risk manage to exhibit cancer resistance, with the ultimate goal of uncovering novel therapies for humans. Building on these foundational insights, we propose expanding the research focus to species that, despite possessing traits beyond size and longevity that theoretically increase their cancer risk, exhibit unexpected cancer resistance. Testing Peto's paradox without interference from transient dynamics also requires considering species that are at an equilibrium between cancer risks and defenses, which is increasingly challenging due to anthropogenic activities. Additionally, we argue that transmissible cancers could significantly help in understanding how the metastatic process might be naturally suppressed. This research perspective is timely and aims to support the continued and in-depth identification of anti-cancer adaptations retained throughout evolution in the animal kingdom., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE).)

Background: The burden of chronic kidney disease is increasing, driven by population aging and the increase in risk factors. In-centre haemodialysis (HD), which accounts for most of the environmental impact of kidney replacement therapy, is a power-hungry, water-hungry and a waste-generating intervention., Methods: Here we characterize the environmental impact of 20 HD centres over 5 years and its modulation by operational changes (centre size, opening days, geographic location, type of water treatment plant and disinfection, dialysis modalities such as HD versus haemodiafiltration, seasonal variations and the impact of various corrective actions throughout time)., Results: Average water and energy consumption per session were lower in larger centres compared with smaller ones, as well as in centres that operated daily compared with those that opened three times a week (both P  < .05). Seasonality, which depends on the geographic region, had a marked influence ( P  < .001) on water and energy consumption, as does the choice of water treatment plant ( P  < .001). Actions taken in certain centres significantly reduced energy consumption up to 30%, plastic waste up to 65% and hazardous waste up to 63%., Conclusion: Annual monitoring must be performed to detect variations and plans must be designed to reduce the environmental impact. As it is not possible to reduce HD water and energy consumption to zero, implementing targeted actions offers a promising strategy for reducing the environmental burden., Competing Interests: A.O. has received grants from Sanofi; consultancy, speaker fees or travel support from Adviccene, Alexion, Astellas, AstraZeneca, Amicus, Amgen, Bioporto, Boehringer Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Sobi, Menarini, Mundipharma, Kyowa Kirin, Lilly, Freeline, Idorsia, Chiesi, Otsuka, Novo Nordisk, Sysmex, Vifor Fresenius Medical Care Renal Pharma and Spafarma; is Director of the Catedra UAM-AstraZeneca of chronic kidney disease and electrolytes and owns stock in Telara Farma. B.D. has received grants, consultancy, speaker fees or travel support by Kitnewcare, Eu Horizon 2024–2027. M.A. has received grants, consultancy, speaker fees or travel support by Spanish Society of Nephrology, Viphor pharma, Baxter, and Fresenius Medical Care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Efficacy and safety of mirikizumab, a p19-targeted anti-interleukin-23 monoclonal antibody, for moderately to severely active ulcerative colitis was demonstrated previously. We evaluated clinical response, baseline characteristics, and clinical status in patients not responding by 12 weeks (W) of induction who then received extended induction treatment., Method: Patients unresponsive to 300 mg of intravenous (IV) mirikizumab every 4 weeks by W12 received 3 additional 300 mg IV doses every 4 weeks. Week-4 responders received 200 mg mirikizumab every 4 weeks subcutaneously until W52. Patients responding by W12 but subsequently losing response received rescue therapy with 300 mg IV for 3 doses every 4 weeks. Logistic regression modelling was performed for patients not achieving W12 clinical response to assess baseline characteristics and W12 efficacy parameters and potential prognostic factors of clinical response at W24., Results: Of patients not achieving clinical response during induction, 53.7% achieved response following extended induction. After 52W, 72.2%, 43.1%, and 36.1% of patients achieved clinical response, endoscopic, and clinical remission, respectively. Of induction responders who subsequently lost response, 63.2% and 36.8% achieved symptomatic response and remission, respectively, after receiving rescue therapy No prior biologic or tofacitinib treatment, no immunomodulators at baseline, age older than 40 years, and W12 modified Mayo Score improvement were positively associated with a response to extended induction. The safety profile was similar to initial induction, with 38.3% treatment emergent adverse events, mostly mild., Conclusion: With "extended induction," total of 80.3% mirikizumab-treated patients achieved clinical response by W24. Potential prognostic factors determining response include disease severity, disease phenotype, C-reactive protein, and previous biologic therapy., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

γδ T cells play diverse roles in immune responses, producing either IL-17A or IFN-γ. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, Vγ4+ γδ T cells are the main source of IL-17A. In type 1 interferon receptor-deficient (A129) mice with heightened susceptibility, there is an increased frequency of IL-17A-producing γδ T cells. L. amazonensis's lipophosphoglycan induces these IL-17A-producing γδ T cells. Notably, C57Bl/6 mice deficient in γδ T cells or IL-17 receptor exhibit smaller lesions, indicating a pathogenic role of IL-17A-producing γδ T cells in cutaneous leishmaniasis. Conversely, adoptive transfer of FACS-sorted γδ T cells lead to an accumulation of IFN-γ-producing γδ T cells, associated with control of lesion development. On the other hand, adoptive transfer of FACS-sorted IFN- γ- deficient-γδ T cells abolished the control of lesion development. These data demonstrate a pathophysiological dichotomy where IL-17A-producing γδ T cells promote pathogenesis, while IFN-γ-producing γδ T cells offer therapeutic potential in cutaneous leishmaniasis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The study aimed to review a multicentre experience of patients undergoing surgical intervention for infective endocarditis caused by Cutibacterium acnes and to analyse the diagnostic challenges and operative results., Methods: We retrospectively reviewed 8812 patients undergoing cardiac surgery for endocarditis at 12 cardiac surgical departments across Germany. The overall population was divided based on the type of endocarditis (i.e. native and prosthetic valve endocarditis). Primary outcomes were in-hospital mortality, 1- and 5-year survival., Results: Cutibacterium acnes caused endocarditis in 269 patients (3.1%). Median age was 65 years (54-72 years) and 237 (88.1%) were male. We observed significantly higher rates of native valve endocarditis in patients aged 21-40, whereas prosthetic valve endocarditis was more frequent in all other age groups (P < 0.001). The median EuroSCORE II of the cohort was 10.7 (5.0-29.6), with it being significantly higher in the prosthetic valve endocarditis group (P < 0.001). Blood culture-negative infective endocarditis was initially reported in 54.3% of the patients. The in-hospital mortality was comparable between the groups (P = 0.340). Survival at 1 and 5 years was significantly higher in the native valve endocarditis group (P < 0.001)., Conclusions: Cutibacterium acnes causes native valve endocarditis, especially in younger patients. The incidence of endocarditis caused by C.acnes is alarming and is at par with well-known endocarditis pathogens such as the HACEK group. The pathogen has a low virulence and presents with a rather indolent course. The diagnosis of C.acnes endocarditis is challenging and requires a multimodal specialized approach. Surgical treatment is associated with acceptable outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We have subjected several analogs of DNA that have been widely used as antisense oligonucleotide (ASO) inhibitors of gene expression to comparative molecular dynamics (MD) calculations of their ability to form duplexes with DNA and RNA. The analogs included in this study are the phosphorothioate (PS), peptide nucleic acid (PNA), locked nucleic acid (LNA), morpholino nucleic acid (PMO), the 2'-OMe, 2'-F, 2'-methoxyethyl (2'-MOE) and the constrained cET analogs, as well as the natural phosphodiester (PO) as control, for a total of nine structures, in both XNA-DNA and XNA-RNA duplexes. This is intended as an objective criterion for their relative ability to duplex with an RNA complement and their comparative potential for antisense applications. We have found that the constrained furanose ring analogs show increased stability when considering this study's structural and energetic parameters. The 2'-MOE modification, even though energetically stable, has an elevated dynamic range and breathing properties due to the bulkier moiety in the C2' position of the furanose. The smaller modifications in the C2' position, 2'-F, 2'-OMe and PS also form stable and energetically favored duplexes with both DNA and RNA. The morpholino moiety allows for increased tolerance in accommodating either DNA or RNA and the PNA, with the PNA being the most energetically stable, although with a preference for the B-form DNA. In summary, we can rank the overall preference of hybrid strand formations as PNA > cET/LNA > PS/2'-F/2'-OMe > morpholino > 2'-MOE for the efficacy of duplex formation., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Background: Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity., Methods: Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were re-interpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated., Findings: A total of 4,087 women were included, of which 490 had histologically confirmed CIN3 + (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI: 42.5-51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI: 54.2-63.5), p < .0001. The specificity without knowledge of HPV was 89.4% (95% CI: 88.2-90.5), while with knowledge of HPV positivity was 78.9% (95% CI: 77.4-80.4), p < .0001. Performance estimates varied by study centre for cytology without knowing the HPV positivity, (range from 32.8% to 61.5% for sensitivity; range 80.7% to 98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1% to 93.4% for sensitivity; 39.6% to 98.6% for specificity)., Conclusion: The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals., (© The Author(s) 2024. Published by Oxford University Press.)

Neutrophils represent one of the host's first lines of defense against invading pathogens. However, an aberrant activation can cause damage to the host. In the case of respiratory infections with viral or bacterial pathogens, one of the most common complications is the development of acute respiratory distress syndrome, in which neutrophil infiltration into the lung is a hallmark. Neutrophils gain expression of chemokine receptors under inflammatory conditions, and their activation can amplify the neutrophil responses. Earlier studies showed that neutrophils recruited to the lung mucosa during bacterial infection upregulate expression of CCR3 and ex vivo stimulation of CCR3 results in an increased neutrophil activation. Therefore, the modulation of effector functions or migration of neutrophils to target sites through chemokine receptors constitutes an opportunity for pharmacological intervention. We aimed to determine whether the blockade of the CCR3 using the specific antagonist SB-328437 reduces neutrophil recruitment and inflammation in the lung in the lipopolysaccharide (LPS)-induced lung injury model and influenza infection in mice. We found that neutrophils acquire CCR3 expression in the lung alveolar space. The intraperitoneal administration of SB-328437 reduced neutrophil recruitment to the lung alveolar space and reduced tissue damage in both the LPS-induced lung injury model and influenza infection. Moreover, treatment with SB-328437 reduced the percentage of neutrophils producing TNFα and neutrophil activation in the alveolar space. Together, these data suggest that CCR3 blockade might be a pharmacological strategy to prevent the aberrant neutrophil activation that results detrimental for the host but preserves sufficient effector response to control the pathogen., Competing Interests: Conflict of interest statement. No conflicts of interest are declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Successful plant reproduction depends on the adequate development of floral organs controlled by cell proliferation and other processes. The Stigma/style cell-cycle inhibitor 1 (SCI1) gene regulates cell proliferation and affects the final size of the female reproductive organ. To unravel the molecular mechanism exerted by Nicotiana tabacum SCI1 in cell proliferation control, we searched for its interaction partners through semi-in vivo pull-down experiments, uncovering a cyclin-dependent kinase, NtCDKG;2. Bimolecular fluorescence complementation and co-localization experiments showed that SCI1 interacts with NtCDKG;2 and its cognate NtCyclin L in nucleoli and splicing speckles. The screening of a yeast two-hybrid cDNA library using SCI1 as bait revealed a novel DEAD-box RNA helicase (NtRH35). Interaction between the NtCDKG;2-NtCyclin L complex and NtRH35 is also shown. Subcellular localization experiments showed that SCI1, NtRH35, and the NtCDKG;2-NtCyclin L complex associate with each other within splicing speckles. The yeast two-hybrid screening of NtCDKG;2 and NtRH35 identified the conserved spliceosome components U2a', NF-κB activating protein (NKAP), and CACTIN. This work presents SCI1 and its interactors, the NtCDKG;2-NtCyclin L complex and NtRH35, as new spliceosome-associated proteins. Our findings reveal a network of interactions and indicate that SCI1 may regulate cell proliferation through the splicing process, providing new insights into the intricate molecular pathways governing plant development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflict of interest The authors declare no conflicts of interest.

Background and Hypothesis: Low levels of muscle strength and function predict adverse clinical outcomes in patients on hemodialysis; however, reference values remain lacking. We described reference values for handgrip strength, five times sit-to-stand (STS-5), and 4-m gait speed in a large-scale sample in patients on hemodialysis., Methods: Baseline data from the SARCopenia trajectories and associations with adverse clinical outcomes in patients on HemoDialysis (SARC-HD) study were analyzed. Muscle strength was evaluated using handgrip strength and the STS-5, whereas physical performance was evaluated using usual 4-m gait speed before a midweek dialysis session. Sex- and age-specific smoothed reference curves for each test at the 3rd, 15th, 50th, 85th, and 97th percentiles were constructed using generalized additive models for location shape and scale. Comparisons between sex and age were also performed., Results: Data from 1004 patients (39% female; 19 to 96 years; 49% ≥ 60 years) were analyzed. Declines in muscle strength and physical performance were observed with advancing age in both sexes. However, among males, muscle strength and performance were similar between 18 and 49 years of age. Males exhibited substantially greater performance in handgrip strength (10.3 kg, 95% confidence interval (CI) 9.1 to 11.4) and 4-m gait speed (-0.10 seconds, 95% CI: -0.14 to -0.05) compared to females. Older patients, independent of sex, exhibited poorer performance on most tests. Lower handgrip strength in the arm with arteriovenous fistula was observed in both sexes (males -2.3 kg, 95% CI: -2.8 to -1.7; and females -2.1 kg, 95% CI: -2.6 to -1.6)., Conclusion: Reference values obtained in this study may be used in clinical and research settings to identify patients on hemodialysis with low physical function according to sex and age. Future studies should test these reference values as potential predictors of adverse clinical outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Youth psychiatric hospitalizations have been associated with negative outcomes, including premature death and post-discharge self-harm. Identifying risk factors for youth psychiatric hospitalization is crucial for informing prevention strategies. We aimed to evaluate the risk factors for psychiatric hospitalizations among low-income youth in Brazil., Methods: This cohort study used interpersonal violence and psychiatric hospitalization data linked to the 100 Million Brazilian Cohort baseline. We considered 9 985 917 youths aged 5-24 years who enrolled at the baseline, between 2011 and 2018. We estimated the incidence rate (IR) with 95% confidence interval (CI) for psychiatric hospitalization by calculating the number of hospitalizations per person-year in 100 000 individuals at risk. The multilevel, multivariate Cox proportional hazards regression estimated the hazard risks (HR) with 95% CI for psychiatric hospitalization., Results: The IR of psychiatric hospitalization was 12.28 per 100 000 person-years (95% CI, 11.96-12.6). Interpersonal violence victimization was the main risk factor for youth psychiatric hospitalization (HR, 5.24; 95% CI, 4.61-5.96). Other risk factors for psychiatric hospitalization included living with the oldest family member who had low education (HR, 2.51; 95% CI, 2.16-2.91) or was unemployed (HR, 1.49; 95% CI, 1.36-1.62), living with seven or more family members (HR, 1.84; 95% CI, 1.49-2.26) and being male (HR, 1.28; 95% CI, 1.21-1.36)., Conclusions: Urgent action is needed to prevent youth from suffering violence. Addressing this may alleviate the mental health burden in developmental ages, benefiting youth, families and the government through reduced costs in preventable psychiatric hospitalizations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)