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The well-documented relationship between chronological age and the sperm methylome has allowed for the construction of epigenetic clocks that estimate the biological age of sperm based on DNA methylation, which we previously termed sperm epigenetic age (SEA). Our lab demonstrated that SEA is positively associated with the time taken to achieve pregnancy; however, its relationship with semen parameters is unknown. A total of 379 men from the Longitudinal Investigation of Fertility and Environment (LIFE) study, a non-clinical cohort, and 192 men seeking fertility treatment from the Sperm Environmental Epigenetics and Development Study (SEEDS) were included in the study. Semen analyses were conducted for both cohorts, and SEA was previously generated using a machine learning algorithm and DNA methylation array data. Association analyses were conducted via multivariable linear regression models adjusting for BMI and smoking status. We found that SEA was not associated with standard semen characteristics in SEEDS and LIFE cohorts. However, SEA was significantly associated with higher sperm head length and perimeter, the presence of pyriform and tapered sperm, and lower sperm elongation factor in the LIFE study (p < 0.05). Based on our results, SEA is mostly associated with defects in sperm head morphological factors that are less commonly evaluated during male infertility assessments. SEA shows promise to be an independent biomarker of sperm quality to assess male fecundity.

Abstract Background Gestational exposure to ambient air pollution has been associated with adverse health outcomes for mothers and newborns. The placenta is a central regulator of the in utero environment that orchestrates development and postnatal life via fetal programming. Ambient air pollution contaminants can reach the placenta and have been shown to alter bulk placental tissue DNA methylation patterns. Yet the effect of air pollution on placental cell-type composition has not been examined. We aimed to investigate whether the exposure to ambient air pollution during gestation is associated with placental cell types inferred from DNA methylation profiles. Methods We leveraged data from 226 mother–infant pairs in the Programming of Intergenerational Stress Mechanisms (PRISM) longitudinal cohort in the Northeastern US. Daily concentrations of fine particulate matter (PM2.5) at 1 km spatial resolution were estimated from a spatiotemporal model developed with satellite data and linked to womens’ addresses during pregnancy and infants’ date of birth. The proportions of six cell types [syncytiotrophoblasts, trophoblasts, stromal, endothelial, Hofbauer and nucleated red blood cells (nRBCs)] were derived from placental tissue 450K DNA methylation array. We applied compositional regression to examine overall changes in placenta cell-type composition related to PM2.5 average by pregnancy trimester. We also investigated the association between PM2.5 and individual cell types using beta regression. All analyses were performed in the overall sample and stratified by infant sex adjusted for covariates. Results In male infants, first trimester (T1) PM2.5 was associated with changes in placental cell composition (p = 0.03), driven by a decrease [per one PM2.5 interquartile range (IQR)] of 0.037 in the syncytiotrophoblasts proportion (95% confidence interval (CI) [− 0.066, − 0.012]), accompanied by an increase in trophoblasts of 0.033 (95% CI: [0.009, 0.064]). In females, second and third trimester PM2.5 were associated with overall changes in placental cell-type composition (T2: p = 0.040; T3: p = 0.049), with a decrease in the nRBC proportion. Individual cell-type analysis with beta regression showed similar results with an additional association found for third trimester PM2.5 and stromal cells in females (decrease of 0.054, p = 0.024). Conclusion Gestational exposure to air pollution was associated with placenta cell composition. Further research is needed to corroborate these findings and evaluate their role in PM2.5-related impact in the placenta and consequent fetal programming.

Abstract Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p

Abstract Background Recently, it has become possible to collect next-generation DNA sequencing data sets that are composed of multiple samples from multiple biological units where each of these samples may be from a single cell or bulk tissue. Yet, there does not yet exist a tool for simulating DNA sequencing data from such a nested sampling arrangement with single-cell and bulk samples so that developers of analysis methods can assess accuracy and precision. Results We have developed a tool that simulates DNA sequencing data from hierarchically grouped (correlated) samples where each sample is designated bulk or single-cell. Our tool uses a simple configuration file to define the experimental arrangement and can be integrated into software pipelines for testing of variant callers or other genomic tools. Conclusions The DNA sequencing data generated by our simulator is representative of real data and integrates seamlessly with standard downstream analysis tools.

Le carcinome épidermoïde de la vessie est une variété rare de tumeurs vésicales qui représente moins de 5% des cancers de vessie. Son sex ratio est équilibré et la population noire semble préférentiellement atteinte. Sa présentation clinique est non spécifique et dominée par l´hématurie. La résection endoscopique de la vessie avec un examen anathomopathologique permet de poser le diagnostic. Le traitement du carcinome épidermoïde de la vessie reste sujet à de nombreuses controverses du fait de la rareté des cas rapportés dans la littérature. Cependant le traitement de choix semble être une cystectomie totale avec curage ganglionnaire étendu. Nous rapportons une série de 10 cas de carcinome épidermoïde qui ont été traités et suivis au sein de notre service. Notre analyse est basée sur l´évaluation des caractéristiques épidémiologiques, cliniques, anatomo-pathologiques, et thérapeutiques du carcinome épidermoïde de la vessie, ainsi que sur l´étude des aspects évolutifs et des facteurs pronostiques.

Radical prostatectomy is the most common reason for male stress urinary incontinence. It affects around 10% of operated patients and can have a major impact on the quality of life of patients and affect various daily activities. There is still insecurity about its therapeutic management. We report the case of a 72-year-old patient, who underwent a radical prostatectomy 10 years ago, complicated by moderate post-operative urinary incontinence motivating the placement of an Advance sub-urethral sling, who presents for dysuria with micturition burns, the urethral fibroscopy objectify the presence of an erosion of the urethra by the sling under urethral.

L´adénocarcinome primitif de la vessie est une variété rare de tumeurs vésicales qui représente moins de 2% des cancers de la vessie. Il semble atteindre préférentiellement le sexe masculin avec un sexe ratio de 3/1 et un âge moyen de survenu entre 60 ans et 70 ans. Sa présentation clinique est non spécifique et dominée par l´hématurie. La résection endoscopique de la vessie avec un examen anathomopathologique permet de poser le diagnostic. Le traitement de l´adénocarcinome primitif de la vessie reste sujet à de nombreuses controverses du fait de la rareté des cas rapportés dans la littérature. Cependant le traitement de choix semble être une cystectomie totale avec curage ganglionnaire étendu. Nous rapportons une série de 6 cas d´adénocarcinome qui ont été traités et suivis au sein de notre formation. Notre analyse est basée sur l´évaluation des caractéristiques épidémiologiques, cliniques, anatomo-pathologiques, et thérapeutiques de l´adénocarcinome de la vessie, ainsi que sur l´étude des aspects évolutifs et des facteurs pronostiques.

Background. The association of renal cell carcinoma and Kartagener’s syndrome is unusual, and only eleven cases have been reported in the literature. The purpose of this work is to analyze this unusual association of Kartagener’s syndrome and renal cell tumor and to study the main diagnostic and therapeutic aspects through our observation and review of the literature. Case Presentation. We report the case of a 50-year-old patient, with a history of recurrent respiratory infections, in whom a renal tumor was simultaneously diagnosed with Kartagener’s syndrome, represented by situs inversus, bronchiectasia, and chronic sinusitis. The patient was treated by partial nephrectomy, and the histological examination showed a clear cell carcinoma. Through this observation and a review of the literature, we try to analyze this association as well as the main diagnostic and therapeutic aspects. Conclusion. The association of situs inversus and renal cell carcinoma is very rare—preoperative assessment and anatomy knowledge are crucial for a better adaptation of the surgical technique.

In practice, an alliance can be a bond or connection between individuals, families, states, or entities, etc. Formally, a non-empty set of vertices of a graph is a defensive -alliance (resp. an offensive -alliance) if every vertex of (resp. the boundary of ) has at least more neighbors inside of than it has outside of . A powerful -alliance is both defensive -alliance and offensive -alliance. During the last decade there has been a remarkable development on these three kinds of alliances. Due to their variety of applications, the alliances in its broad sense have received a special attention from many scientists and researchers. There have been applications of alliances in several areas such as bioinformatics, distributed computing, web communities, social networks, data clustering, business, etc. Several -alliance numbers have been defined and a huge number of theoretical (algorithmic and computational) results are obtained for various graph classes. In this paper, we present a survey which covers a number of practical applications of alliances and the vast mathematical properties of the three types of -alliances by giving a special attention to the study of the associated -alliance (partition) numbers for different graph classes.

Paleoclimate reconstructions are generally validated on recent periods. To obtain a set of instrumental records at the regional scale, a time series of monthly mean temperatures in Northeastern Canada were interpolated for the 1961-2000 period. Records were provided by 202 meteorological stations. Temperatures derived from a Canadian regional climate model (Climate Model CRCM 4.2.3 from the AMNO domain produced at ∼50 km resolution) were added as secondary information to take into account local heterogeneity and temporal dependencies. Geostatistical interpolation of the measured temperature was calculated using CRCM modelled data as a covariable and then compared to an ordinary kriging performed on a time series of mean temperature anomalies. Spherical distances between locations were calculated taking into account the curvature of the Earth with monthly semivariances being modelled using Cauchy variograms. Mean absolute error values (1.5 ± 1.2 °C) were calculated for the whole period using cross-validation procedures. Errors were found to have the same order of magnitude in the central part of the study area where few recorded temperatures were available. Monthly mean temperature grids are publicly available through the Institut National de la Recherche Scientifique (http://url.in.rs/3P). Copyright © 2012 Royal Meteorological Society [ABSTRACT FROM AUTHOR]

The fragmentation of 95 MeV/u 12C and 75 MeV/u 13C projectiles, interacting with natural targets of different elements (9Be, natCu and 197Au for 12C, and 9Be, natNi, and 181Ta for 13C) and of various thicknesses has been investigated at GANIL, using the doubly achromatic magnetic spectrometer LISE. The projectile-like fragments transmitted at 0° have been analysed using a silicon ΔE-E telescope and the ΔE-time-of-flight method. The results obtained with the thinnest targets are discussed in the scope of radioactive nuclear beam production. The fragment momentum distributions can be fitted by Gaussian peaks associated with exponential tails towards low momentum values. The experimental production yields are compared with the results of the simulation code LISE. It appears that this code reproduces satisfactorily the yields of nuclei close to the stability line, but strongly overestimates the production of very neutron-deficient nuclei. [ABSTRACT FROM AUTHOR]

We study a nonlinear multiple objective fractional programming with inequality constraints where each component of functions occurring in the problem is considered semidifferentiable along its own direction instead of the same direction. New Fritz John type necessary and Karush-Kuhn-Tucker type necessary and sufficient efficiency conditions are obtained for a feasible point to be weakly efficient or efficient. Furthermore, a general Mond-Weir dual is formulated and weak and strong duality results are proved using concepts of generalized semilocally V-type I-preinvex functions. This contribution extends earlier results of Preda (2003), Mishra et al. (2005), Niculescu (2007), and Mishra and Rautela (2009), and generalizes results obtained in the literature on this topic.

Prostate cancer remains a significant health challenge, being the most prevalent non-cutaneous cancer in men worldwide. This review discusses the critical advancements in biomarker discovery using single-omics and multi-omics approaches. Multi-omics, integrating genomic, transcriptomic, proteomic, metabolomic, and epigenomic data, offers a comprehensive understanding of the molecular heterogeneity of prostate cancer, leading to the identification of novel biomarkers and therapeutic targets. This holistic approach not only enhances the specificity and sensitivity of prostate cancer detection but also supports the development of personalized treatment strategies. Key studies highlighted include the identification of novel genes, genetic mutations, peptides, metabolites, and potential biomarkers through multi-omics analyses, which have shown promise in improving prostate cancer management. The integration of multi-omics in clinical practice can potentially revolutionize prostate cancer prognosis and treatment, paving the way for precision medicine. This review underscores the importance of continued research and the application of multi-omics to overcome current challenges in prostate cancer diagnosis and therapy.

Objectives: To conduct a systematic literature search to identify currently used classifications of acute non-contact muscle injuries in sporting adults., Designs: Scoping review., Methods: A systematic literature search from January 1, 2010 to April 19, 2022 of Medline and SPORTDiscus yielded 13,426 articles that were screened for eligibility. Findings from included studies were qualitatively synthesized. Classifications and their grading, as well as outcomes and definitions were extracted., Results: Twenty-four classifications were identified from the 37 included studies, most of which had low evidence study designs. Majority (57 %) of classifications were published after 2009 and were mostly developed for hamstring or other lower limb injuries. The six most cited classifications accounted for 70 % of the reports (BAMIC, modified Peetrons, Munich, Cohen, Chan and MLG-R). Outcome reporting was sparse, making it difficult to draw conclusions. Still, significant relationships between grading and time to return to play were reported for the BAMIC, modified Peetrons, Munich and Cohen classifications. Other classifications either had a very low number of reported associations, reported no associations, reported inconclusive associations, or did not report an assessment of the association. Other outcomes were poorly investigated., Conclusions: There is no agreed-upon use of muscle classification, and no consensus on definitions and terminology. As a result, reported outcomes and their relationship to severity grading are inconsistent across studies. There is a need to improve the generalizability and applicability of existing classifications and to refine their prognostic value. High-level evidence studies are needed to resolve these inconsistencies., Competing Interests: Declaration of interest statement None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Registries of congenital anomalies (CAs) play a key role in the epidemiological surveillance of CAs. The objective was to estimate the prevalence of CAs and proportions of prenatal diagnosis, terminations of pregnancy for fetal anomaly (TOPFA) and infant mortality in the Paris Registry of Congenital Malformations (remaPAR) over 40 years, from 1981 to 2020., Material and Methods: remaPAR records all births (live births, stillbirths ≥22 weeks of gestation and TOPFA at any gestational age) with CAs detected prenatally until the early neonatal period. We estimated the prevalence of CAs and proportions of prenatal diagnosis, TOPFA and infant mortality, overall and for a selected group of CAs in 3-year intervals., Results: The prevalence of CAs remained stable during the study period: 2.9 % of total births and 2.1 % of live births. Genetic anomalies were the most frequent subgroup (about 23 %), followed by congenital heart defects (about 22 %) and limb defects (about 20 %). Among non-genetic anomalies, the prevalence per 10,000 births was the highest for hypospadias (about 18 %) and the lowest for bilateral renal agenesis (about 1 %). Prenatal diagnoses increased from about 17 % in the 1980s to approximately 70 % in the most recent period (2018-2020), whereas the proportion of early TOPFA <16 weeks of gestation increased from 0.4 % to 14 %. Infant mortality ranged from 0 % for transverse limb reduction defects to 86 % for hypoplastic left heart syndrome., Conclusion: The overall prevalence of CAs was fairly stable in Paris from 1981 to 2020. Prenatal diagnoses substantially increased, accompanied by much smaller increases in TOPFA., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The pathogenic fungus Candida albicans is a leading agent of death in immunocompromised individuals with a growing trend of antifungal resistance., Methods: The purpose is to induce resistance to drugs in a sensitive C. albicans strain followed by whole-genome sequencing to determine mechanisms of resistance. Strains will be assayed for pathogenicity attributes such as ergosterol and chitin content, growth rate, virulence, and biofilm formation., Results: We observed sequential increases in ergosterol and chitin content in fluconazole-resistant isolates by 78% and 44%. Surface thickening prevents the entry of the drug, resulting in resistance. Resistance imposed a fitness trade-off that led to reduced growth rates, biofilm formation, and virulence in our isolates. Sequencing revealed mutations in genes involved in resistance and pathogenicity such as ERG11 , CHS3 , GSC2 , CDR2 , CRZ2 , and MSH2 . We observed an increase in the number of mutations in key genes with a sequential increase in drug-selective pressures as the organism increased its odds of adapting to inhospitable environments. In ALS4 , we observed two mutations in the susceptible strain and five mutations in the resistant strain., Conclusion: This is the first study to induce resistance followed by genotypic and phenotypic analysis of isolates to determine mechanisms of drug resistance.

SAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old girl, from a consanguineous Lebanese family, was included in this study. She presents with pre- and post-natal growth retardation, recurrent fevers, persistent diarrhea, elevated CRP and intermittent hypoglycemia. Whole genome sequencing revealed a homozygous frameshift variant in SAMD9 (NM&#95;017654.4: c.480&#95;481del; p.Val162Ilefs*5) in the proband. Sanger sequencing confirms its segregation with the disease in the family, and immunoblotting showed that the detected variant abolishes SAMD9 expression in the patient. Our findings expand the clinical spectrum linked to SAMD9 and highlight the importance of investigating further cases with mutations in this gene, as this will pave the way towards the understanding of the pathways driving these diseases., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Prostate cancer (PCa) is the second most common malignancy and the fifth leading cause of cancer death in men worldwide. Despite its prevalence, the highly heterogenic PCa has shown difficulty to establish representative cell lines that reflect the diverse phenotypes and different stages of the disease in vitro and hence hard to model in preclinical research. The patient-derived organoid (PDO) technique has emerged as a groundbreaking three-dimensional (3D) tumor modeling platform in cancer research. This versatile assay relies on the unique ability of cancer stem cells (CSCs) to self-organize and differentiate into organ-like mini structures. The PDO culture system allows for the long-term maintenance of cancer cells derived from patient tumor tissues. Moreover, it recapitulates the parental tumor features and serves as a superior preclinical model for in vitro tumor representation and personalized drug screening. Henceforth, PDOs hold great promise in precision medicine for cancer. Herein, we describe the detailed protocol to establish and propagate organoids derived from isolated cell suspensions of PCa patient tissues or cell lines using the 3D semisolid Matrigel™-based hanging-drop method. In addition, we highlight the relevance of PDOs as a tool for evaluating drug efficacy and predicting tumor response in PCa patients., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)