Tag: pubmed

Hum Reprod. 2025 Nov 6:deaf207. doi: 10.1093/humrep/deaf207. Online ahead of print.

ABSTRACT

STUDY QUESTION: Is there a relationship between the mitochondrial activity and the meiotic progression of oocytes from germinal vesicle (GV) to metaphase II (MII) stages in young and advanced maternal age (AMA) women?

SUMMARY ANSWER: Poor mitochondrial metabolism impairs the meiotic progression of human GV oocytes, contributing to a lower oocyte maturation capacity of AMA oocytes.

WHAT IS KNOWN ALREADY: AMA oocytes are characterized by diminished quality, mostly due to the higher rates of chromosomal segregation errors occurring during meiosis I. Another hallmark of AMA oocytes is impaired mitochondrial metabolism. Studies in mice have suggested a link between metabolic dysfunction and meiotic failure, but this relationship has not been fully elucidated in humans. Metabolic dynamics can be visualized by indirect measurements through mitochondrial staining and quantified more directly using fluorescence lifetime imaging microscopy (FLIM). This live-imaging approach can generate metabolic timelapse profiles of oocytes throughout meiosis. In the present study, we explored mitochondrial distribution and functionality in human oocytes at the GV and MII stages, obtained from young and AMA women, to establish the role of mitochondrial metabolism in meiosis progression.

STUDY DESIGN, SIZE, DURATION: A total of 340 GV oocytes from young (≤34 years) and AMA (>37 years) women were included in the study. Denuded GVs were matured in vitro in G2-plus medium for 30 h. Maturation was determined by the presence of the extruded first polar body (PB1). The collected oocytes were processed for mitochondrial protein imaging (n = 80), or for live imaging (n = 171). Moreover, 89 oocytes were used for loss-of-function analysis by treating young GVs with 1 μM trifluoromethoxy-carbonylcyanide-phenylhydrazone (FCCP) for 30 min before in vitro maturation.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The proteins dihydrolipoamide-S-acetyltransferase (D-LAT) and translocase-of-outer mitochondrial-membrane (TOMM20) were analyzed in young and AMA oocytes by immunofluorescence to assess mitochondrial activity and localization, respectively. Fluorescence mean intensities (arbitrary-unit, AU) were quantified with ImageJ and compared by t-test; maturation rates were compared by chi-squared test. FLIM comprehensive metabolism (NAD(P)H; FAD+) was taken at GV stage. Different FLIM parameters (fluorescence intensity, fraction bound, short/long lifetime) and the Redox ratio (NAD(P)H intensity/FAD+ intensity) were evaluated.

MAIN RESULTS AND THE ROLE OF CHANCE: The findings revealed that active mitochondria are specifically localized in the subcortical area, while mitochondria in general are distributed across the whole oocyte. This pattern was substantially maintained in AMA oocytes, which were in turn characterized by a lower mitochondrial activity (D-LAT intensity of 78 614 ± 58 534 AU in young, 12 517 ± 10 187 AU in AMA, P = 0.003), while a lower number of mitochondria was observed In AMA patients but the difference did not reach statistical significance (TOMM20 intensity of 61 674 ± 24 322 AU in young, 32 186 ± 33 414 AU in AMA, P = 0.195). Using non-invasive FLIM, we assessed the metabolic dynamics of maturing oocytes (Redox ratio in young 2e + 00 ± 0.15, in AMA 1e + 00 ± 0.16, P = 2.969e-05), confirming a similar pattern observed by immunofluorescence. Specifically, FLIM microscopy revealed that GV oocytes from young women slightly increased their metabolism, by 4% on average, after the GV breakdown, and the increase was very consistent across different oocytes. On the contrary, in AMA maturing oocytes, little to no increase in metabolism was observed; they were characterized instead by higher variability, and more AMA oocytes failed to successfully reach the MII stage [AMA oocytes (62.3%; 38/61) compared with young oocytes (86.3%; 63/73; P = 0.002). These differential trends observed in AMA oocytes compared to the young oocytes suggest that impaired metabolic activity significantly compromises maturation capacity, revealing a functional link between adequate metabolic levels and successful meiosis progression.

LIMITATIONS, REASONS FOR CAUTION: Maturation rates were assessed by the presence of an extruded PB1 and variations in spindle assembly timings may have been overlooked. The quantification of mitochondrial activity in loss-of-function studies was assessed only by immunofluorescence staining. Additionally, the oocytes included in the present study were collected from women who underwent ovarian stimulation and may not faithfully recapitulate physiological maturation.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrate the presence of a functional link between oocyte mitochondrial metabolism and meiosis progression, which may contribute to the decline of oocyte quality with aging. Overall, we provided evidence to understand the biological mechanisms in mitochondrial metabolism that might contribute to driving the decay in oocyte quality in AMA women.

STUDY FUNDING/COMPETING INTEREST(S): This project received intramural funding from the Eugin Group and funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 860960. T.S. is a former owner and former stock owner of Optiva Fertility Inc (company closed) and filed two patents for Optiva Fertility Inc (both abandoned). D.S.: Presenter EMD Senoro and Dep. Editor of Human Reproduction. All of the other authors (S.P., M.M., M.B., E.I., M.P., R.V., and F.Z.) have no conflicts of interest to declare. All of the authors contributed substantially to the manuscript and approve its submission.

TRIAL REGISTRATION NUMBER: N/A.

PMID:41206610 | DOI:10.1093/humrep/deaf207

Hum Reprod. 2025 Nov 6:deaf210. doi: 10.1093/humrep/deaf210. Online ahead of print.

ABSTRACT

STUDY QUESTION: Does the interaction between CFTR and AQP7 in human spermatozoa play a role in the molecular mechanisms underlying sperm motility?

SUMMARY ANSWER: CFTR inhibition reduces sperm motility and AQP7-mediated glycerol permeability in human spermatozoa, and CFTR and AQP7 co-localize in the equatorial segment of the sperm head, with in silico modeling suggesting a potential interaction between these proteins.

WHAT IS KNOWN ALREADY: CFTR modulates the permeability of aquaglyceroporins in multiple tissues, and their interaction is mediated by the scaffolding protein NHERF1. AQP7-mediated glycerol permeability correlates with sperm motility.

STUDY DESIGN, SIZE, DURATION: Semen samples were collected from normozoospermic men (normal motility; n = 33) and men with asthenozoospermia (reduced motility; n = 15) at a fertility clinic between September 2020 and January 2021.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Isolated sperm from men with normozoospermia were used to study the effect of CFTR on sperm motility (N = 10) and glycerol permeability (N = 23). Sperm from 14 asthenozoospermic samples and 13 normozoospermic samples were used to compare the effect of CFTR on AQP7-mediated glycerol permeability, after screening for the absence of common CFTR gene variants. Sperm membrane permeability to glycerol was measured using stopped-flow light scattering, and the effect of CFTR conductance was modulated using a specific inhibitor (CFTRinh172). The interaction between CFTR and AQP7 was investigated using co-immunofluorescence, proximity ligation assay, and in silico approaches like ColabFold and GROMACS. Gaussian distribution of the data was measured by the Shapiro-Wilk normality test. Data showing non-normal distribution was treated with the Kruskal-Wallis test, whereas normal distribution data were treated with an ordinary one-way ANOVA. Comparisons between normozoospermic and asthenozoospermic groups were performed using an unpaired two-tailed Mann-Whitney U test. A P-value less than 0.05 was considered significantly different.

MAIN RESULTS AND THE ROLE OF CHANCE: CFTR inhibition negatively affected sperm motility (0.53 ± 0.11-fold variation to control, P < 0.05) and AQP7-mediated glycerol permeability (0.459-fold [0.314; 0.537] variation to control, P < 0.01). Despite this, the effect of CFTR dysfunction on AQP7-mediated glycerol permeability of sperm from normo- versus asthenozoospermic samples did not reach statistical significance (P = 0.068) due to low statistical power, but a tendency was apparent. A larger sample size is needed to confirm this trend. CFTR and AQP7 (the main glycerol diffuser in human sperm) co-localize and are in proximity in the midpiece and in the equatorial section of the sperm head in human sperm. In silico analysis supports the interaction of CFTR with AQP7 intermediated by NHERF1, indicating a mechanism of physical modulation of AQP7 permeability by CFTR.

LIMITATIONS, REASONS FOR CAUTION: Only cystic fibrosis-associated CFTR variants were screened during this study; the presence of assumed benign variants that could slightly decrease CFTR function may have impacted the results. Glycerol permeability was measured indirectly by assuming its proportionality with the change in sperm volume through time after the osmotic shock. A larger sample size would be needed to confirm the trends that did not reach statistical significance. Furthermore, pharmacological assays were conducted in a non-nutrient buffer to specify direct effects of the channel; this condition differs from physiological media and represents a specific limitation of this study.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that a novel mechanism based on the functional and physical interaction between CFTR and AQP7 may underlie some cases of asthenozoospermia and idiopathic male infertility; the results also increase our knowledge of the molecular mechanisms governing sperm motility.

STUDY FUNDING/COMPETING INTEREST(S): This research was funded by Fundação para a Ciência e a Tecnologia (FCT) to UMIB (UIDB/00215/2020, and UIDP/00215/2020), ITR-Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020), and the post-graduate student João C. Ribeiro (UI/BD/150749/2020). The work was co-funded by FEDER through the COMPETE/QREN, FSE/POPH, and POCI-COMPETE 2020 (POCI-01-0145-FEDER-007491) funds. P.F.O. is funded by national funds through FCT, I.P., under the Scientific Employment Stimulus-Institutional Call-reference CEEC-INST/00026/2018. This work also received support and help from FCT/MCTES to LAQV-REQUIMTE (LA/P/0008/202-DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020-DOI 10.54499/UIDP/50006/2020, and UIDB/50006/2020-DOI 10.54499/UIDB/50006/2020) and to iBiMed (UIDB/04501/2020-DOI 10.54499/UIDB/04501/2020 and UIDP/04501/2020-DOI 10.54499/UIDP/04501/2020), through national funds. There are no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:41206608 | DOI:10.1093/humrep/deaf210

Gigascience. 2025 Nov 6:giaf140. doi: 10.1093/gigascience/giaf140. Online ahead of print.

ABSTRACT

Existing Python libraries and tools lack the ability to efficiently compute statistical test results for large datasets in the presence of missing values. This presents an issue as soon as constraints on runtime and memory availability become essential considerations for a particular use case. Relevant research areas where such limitations arise include interactive tools and databases for exploratory analysis of biomedical data. To address this problem, we present the Python package NApy, which relies on a Numba and C++ backend with OpenMP parallelization to enable scalable statistical testing for mixed-type datasets in the presence of missing values. Both with respect to runtime and memory consumption, NApy outperforms competitor tools and baseline implementations with naïve Python-based parallelization by orders of magnitude, thereby enabling on-the-fly analyses in interactive applications. NApy is publicly available at https://github.com/DyHealthNet/NApy.

PMID:41206544 | DOI:10.1093/gigascience/giaf140

J Anim Sci. 2025 Nov 6:skaf394. doi: 10.1093/jas/skaf394. Online ahead of print.

ABSTRACT

Accurate live prediction of carcass and meat quality traits is essential for enhancing product consistency and production efficiency in the lamb industry. Traditional assessments rely on postmortem measurements, which require animal slaughter and thus cannot be used for repeated measurements or on-farm decision making. In this study, we developed a modified bioelectrical impedance analysis (BIA) system incorporating multi-site needle electrodes to collect full-body resistance data from 204 live crossbred lambs. These electrical features, combined with basic body size measurements, were used to construct predictive models for 10 carcass and meat quality traits using linear regression and six machine learning algorithms. Among these, multiple linear regression showed the best overall performance, with R2 values exceeding 0.70 for traits such as carcass weight, abdominal fat, and meat color. Feature importance analysis indicated that resistance values from specific anatomical regions were strongly associated with fat deposition, muscle structure, and water-holding capacity. Our findings demonstrate that this integrated BIA-based approach provides a practical, low-cost, and minimally invasive method for live-animal phenotyping, offering valuable applications in on-farm meat quality screening, precision nutrition, and genetic selection programs.

PMID:41206537 | DOI:10.1093/jas/skaf394

Ultrasound Obstet Gynecol. 2025 Nov 8. doi: 10.1002/uog.70100. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the effectiveness and safety of oral misoprostol vs vaginal dinoprostone for the induction of labor (IOL) using an individual participant data (IPD) meta-analysis.

METHODS: We used a Cochrane review and searched Ovid MEDLINE, Ovid Embase, Ovid Emcare, CINAHL Plus, Scopus and ClinicalTrials.gov to identify randomized controlled trials (RCTs) that compared oral misoprostol with vaginal dinoprostone for IOL in viable singleton pregnancies. We invited the authors of eligible trials to share their anonymized data. Primary outcomes were vaginal delivery, a composite measure of adverse maternal outcomes and a composite measure of adverse perinatal outcomes. IPD meta-analysis was conducted using a two-stage random-effects model. An intention-to-treat approach was used for all analyses. Aggregate-data meta-analysis was undertaken with RCTs stratified by Trustworthiness in RAndomised Clinical Trials (TRACT) score.

RESULTS: Of 18 eligible RCTs, eight provided IPD, of which five (1892 participants) met the TRACT criteria for trustworthiness. IPD meta-analysis showed similar rates of vaginal delivery after IOL with oral misoprostol or vaginal dinoprostone (odds ratio (OR), 0.99 (95% CI, 0.80-1.22); I² = 0%). The rates of composite adverse perinatal outcome (adjusted odds ratio (aOR), 1.02 (95% CI, 0.61-1.72); I² = 0%) and composite adverse maternal outcome (aOR, 1.39 (95% CI, 0.72-2.69); I² = 0%) were also comparable between the groups. Of 10 RCTs that did not share IPD, seven met the TRACT criteria. Aggregate-data meta-analysis of the 12 RCTs (five with IPD and seven without IPD) meeting the trustworthiness criteria also showed comparable rates of vaginal delivery after oral misoprostol and after vaginal dinoprostone (OR, 1.08 (95% CI, 0.92-1.27)). In contrast, six studies not meeting the trustworthiness criteria (three with and three without IPD) reported a higher rate of vaginal delivery following oral misoprostol (OR, 1.34 (95% CI, 1.22-1.48)), resulting in an inflated overall estimate of the vaginal delivery rate after oral misoprostol based on all data (OR, 1.19 (95% CI, 1.05-1.36)).

CONCLUSION: IOL with oral misoprostol or vaginal dinoprostone results in comparable rates of vaginal delivery and composite perinatal and maternal adverse outcomes. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

PMID:41206516 | DOI:10.1002/uog.70100

Biophys J. 2025 Nov 7:S0006-3495(25)00740-4. doi: 10.1016/j.bpj.2025.11.005. Online ahead of print.

ABSTRACT

A high degree of structural complexity arises in dynamic neuronal dendrites due to extensive branching patterns and diverse spine morphologies, which enable the nervous system to adjust function, construct complex input pathways and thereby enhance the computational power of the system. Recognition of pathological changes due to neurodegenerative disorders is of crucial importance due to the determinant role of dendrite morphology in the functionality of the nervous system. Nevertheless, direct noninvasive measurements to collect adequate structural data in a reasonable time are currently not feasible. Here, we present a stochastic coarse-grained framework based on first-passage analysis to infer key dendritic morphological features affected by neurodegenerative diseases-including the density and size of spines, the extent of the tree, and the segmental increase of dendrite shaft diameter towards the soma-from the statistical characteristics of a measurable temporary signal generated by tracers that have diffusively passed through the complex dendritic structure. Thus, our theoretical approach can provide a noninvasive route to link dendritic morphology with possible accessible readouts in neurodegenerative disease monitoring. As a prospective application, we discuss how externally detectable signals could be realized in practice, suggesting potential pathways toward experimental implementation.

PMID:41206512 | DOI:10.1016/j.bpj.2025.11.005

Mil Med. 2025 Nov 6:usaf549. doi: 10.1093/milmed/usaf549. Online ahead of print.

ABSTRACT

BACKGROUND: The U.S. Emergency Medical Service (EMS) system faces persistent workforce shortages. Thousands of military personnel transition out of service each year with EMS-related training, yet little is known about their roles or willingness to pursue civilian EMS careers. Despite low national unemployment rates among veterans, many remain underutilized in healthcare occupations. We aim to describe the current roles of nationally certified military EMS clinicians and assess their interest in transitioning to civilian EMS employment.

MATERIALS AND METHODS: We conducted a cross-sectional survey of National Registry-certified EMS clinicians actively serving in the U.S. military. Respondents recertifying between October 2021 and April 2022 were invited to complete a voluntary, one-time survey. The analytic sample included military-affiliated clinicians aged 18-85 who reported an EMS job role and responded to a question about interest in civilian EMS transition. Descriptive statistics multivariable Poisson regression with robust standard errors were used to characterize EMS roles and identify factors associated with transition interest. Referent groups for categorical variables were selected based on the subgroup with the largest number of respondents.

RESULTS: Among 1,937 included respondents, the median age was 32 years (interquartile range: 27-40), and most were male (66.6%) and White, non-Hispanic (58.3%). Respondents represented all major military branches, with the largest proportion from the Air Force (60.3%). Most held emergency medical technician certification (82.5%). Overall, 60.5% expressed interest in civilian EMS employment after separation. Transition interest was highest among clinicians in the Army (prevalence ratio: 1.23; 95% confidence interval: 1.11-1.36), Navy (1.31; 1.17-1.45), and Coast Guard (1.13; 1.01-1.27) compared to the Air Force. Those in educational or non-traditional roles had higher prevalence of interest than those in hospital-based roles, while older clinicians had significantly lower prevalence of interest.

CONCLUSION: Findings from this convenience sample suggest that a substantial portion of military EMS clinicians, particularly younger personnel and those affiliated with the Army, Navy, and Coast Guard, may be interested in transitioning to civilian EMS roles. While not representative of all military EMS personnel, these patterns highlight the potential utility of structured veteran-to-civilian EMS pathways. Future research using more representative sampling strategies is needed to confirm these trends and inform workforce development efforts.

PMID:41206493 | DOI:10.1093/milmed/usaf549

Int J Soc Psychiatry. 2025 Nov 8:207640251379130. doi: 10.1177/00207640251379130. Online ahead of print.

ABSTRACT

The study investigates how social media affects privacy perceptions among university students, combining a historical perspective on privacy with contemporary data on young adults; interactions with digital platforms. An online survey of 219 students (122 women and 97 men) assessed their awareness of social media’s overt and hidden influences on personal decisions and privacy concerns. Statistical analyses included t-tests, Wilcoxon-Mann-Whitney tests, χ² tests, and correlation measures. Results highlighted significant gender differences. Women were more aware of social media’s influence (54.9% vs. 38.1% of men) and expressed greater privacy concerns (41.8% vs. 36.1%). These findings emphasize the need for gender-sensitive educational initiatives to improve privacy awareness and inform policies to safeguard user rights. Further research is recommended to explore broader demographics for a comprehensive understanding of social media’s impact on privacy.

PMID:41206484 | DOI:10.1177/00207640251379130

Biostatistics. 2024 Dec 31;26(1):kxaf028. doi: 10.1093/biostatistics/kxaf028.

ABSTRACT

Disease mapping analyses the distribution of several disease outcomes within a territory. Primary goals include identifying areas with unexpected changes in mortality rates, studying the relation among multiple diseases, and dividing the analysed territory into clusters based on the observed levels of disease incidence or mortality. In this work, we focus on detecting spatial mortality clusters, that occur when neighbouring areas within a territory exhibit similar mortality levels due to one or more diseases. When multiple causes of death are examined together, it is relevant to identify not only the spatial boundaries of the clusters but also the diseases that lead to their formation. However, existing methods in literature struggle to address this dual problem effectively and simultaneously. To overcome these limitations, we introduce perla, a multivariate Bayesian model that clusters areas in a territory according to the observed mortality rates of multiple causes of death, also exploiting the information of external covariates. Our model incorporates the spatial structure of data directly into the clustering probabilities by leveraging the stick-breaking formulation of the multinomial distribution. Additionally, it exploits suitable global-local shrinkage priors to ensure that the detection of clusters depends on diseases showing concrete increases or decreases in mortality levels, while excluding uninformative diseases. We propose a Markov chain Monte Carlo algorithm for posterior inference that consists of closed-form Gibbs sampling moves for nearly every model parameter, without requiring complex tuning operations. This work is primarily motivated by a case study on the territory of a local unit within the Italian public healthcare system, known as ULSS6 Euganea. To demonstrate the flexibility and effectiveness of our methodology, we also validate perla with a series of simulation experiments and an extensive case study on mortality levels in U.S. counties.

PMID:41206482 | DOI:10.1093/biostatistics/kxaf028

Nucleic Acids Res. 2025 Nov 6:gkaf1146. doi: 10.1093/nar/gkaf1146. Online ahead of print.

ABSTRACT

The ProteomeXchange consortium of proteomics resources (http://www.proteomexchange.org) was established to standardize open data practices in the mass spectrometry (MS)-based proteomics field. Here, we describe the main developments in ProteomeXchange in the last 3 years. The six member databases of ProteomeXchange, spread out in three different continents, are the PRIDE database, PeptideAtlas, MassIVE, jPOST, iProX, and Panorama Public. We provide updated data submission statistics, showcasing that the number of datasets submitted to ProteomeXchange resources has continued to accelerate every year. Through June 2025, 64 330 datasets had been submitted to ProteomeXchange resources, and from those, 30 097 (47%) just in the last 3 years. We also report on the improvements in the support for the standards developed by the Proteomics Standards Initiative, e.g. for Universal Spectrum Identifiers and for SDRF (Sample and Data Relationship Format)-Proteomics. Additionally, we highlight the increase in data reuse activities of public datasets, including targeted reanalyses of datasets of different proteomics data types, and the development of novel machine learning approaches. Finally, we summarize our plans for the near future, covering the development of resources for controlled-access human proteomics data, and for the support of non-MS proteomics approaches.

PMID:41206473 | DOI:10.1093/nar/gkaf1146