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Background: Physical therapy is an ever-evolving profession. To improve research efficiency, it is crucial to identify knowledge gaps and establish research priorities., Objective: To review priorities for physical therapy research, and to summarize the evidence into a global research agenda. As a secondary aim we sought to compare the priorities across studies., Methods: We conducted a scoping review with searches in PubMed, Web of Science, and Google Scholar to gather studies and grey literature. Studies were included if they involved physical therapists, physical therapy researchers, patients, or policymakers who determined a research agenda or conducted a study on priority setting in physical therapy research. Content analysis was performed by two independent reviewers to gather research priorities into main topics for a global research agenda., Results: Twenty-five records were included, most being original articles (n = 19), from high-income countries (n = 25). Nine studies established generic priorities for physical therapy research, while the remaining were dedicated to physical therapy specific fields. A total of 551 priorities were established since 2000 for general physical therapy and 7 specific physical therapy areas. A global research agenda was established with 9 priority categories for future research. Cost and effectiveness studies were the more frequently prioritized research priorities., Conclusion: This review synthesized the literature on priorities for physical therapy research and provided a global physical therapy research agenda. These 9 priority categories can now be used to design future physical therapy studies and channel research efforts into questions that are relevant for multiple stakeholders and nationalities., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Failure to rescue after elective surgery is associated with increased healthcare costs. These costs are poorly understood and have not been reported for colorectal surgery. This study aimed to assess the incremental costs of failure to rescue after elective colorectal surgery., Methods: This was a retrospective study of adult patients identified in the National Inpatient Sample from 2016 to 2019 who underwent an elective colectomy or proctectomy. Patients were stratified into 4 groups: uneventful recovery, successfully rescued, failure to rescue, and died without rescue attempts. "Rescue" was defined as admissions with ≥1 procedure code ≥1 day after the initial procedure. The primary outcome was total admission costs., Results: Of 451,490 admissions for elective colorectal resection, 94.6% had an uneventful recovery, 4.8% were successfully rescued, 0.4% were failure to rescue, and 0.3% died without rescue attempts. The median total hospital cost for the uneventful recovery cohort was $16,751 (IQR, $12,611-$23,116), for the successfully rescued cohort was $42,295 (IQR, $27,959-$67,077), for the failure-to-rescue cohort was $53,182 (IQR, $30,852-$95,615), and for the died without attempted rescue cohort was $29,296 (IQR, $19,812-$45,919). When comparing cost quantiles by regression analysis, failure-to-rescue patients had significantly higher costs than the successfully rescued patients for the last 3 quantiles (fifth quantile [90th percentile], $163,963 vs $106,521; P < .001)., Conclusion: Across a nationally representative cohort, the median total hospital costs for patients who failed to be rescued were $10,887 more than for those who were successfully rescued. These findings emphasize the importance of shared decision making and medical futility and highlight opportunities for resource optimization after postoperative complications., (Published by Elsevier Inc.)

Per- and polyfluoroalkyl substances (PFAS), known colloquially as "forever chemicals", have been associated with adverse human health effects and have contaminated drinking water supplies across the United States owing to their long-term and widespread use. People in the United States may unknowingly be drinking water that contains PFAS because of a lack of systematic analysis, particularly in domestic water supplies. We present an extreme gradient boosting model for predicting the occurrence of PFAS in groundwater at the depths of drinking water supply for the conterminous United States. Our model results indicate that 71 to 95 million people in the conterminous United States potentially rely on groundwater with detectable concentrations of PFAS for their drinking-water supplies prior to any treatment.

Even though the use of organochlorine pesticides has been prohibited since the last century their presence is still being recorded around the world. In the upper La Antigua watershed, Veracruz, Mexico we have reported concentrations of these contaminants in different compartments of the riverine ecosystems. This is of relevance due to their potential disruptive endocrine effect on the vertebrates drinking the water or feeding in the riverine area. In this study we evaluated concentrations of organochlorine pesticides (OCPs) in streams running throughout mountain cloud forest and two different types of land use, pasture lands and coffee plantations. Water and periphyton samples were collected during the wet and the dry seasons from streams located in independent micro-basins. Spatial explicit analyzes show that the concentrations measured are independent of the distribution of the streams in the geographical area sampled. However seasonal differences were found during the dry season in the water and during the rainy season in periphyton. While OCPs in water support the idea that micro-basins can be used as independent monitoring units, OCPs in periphyton can be indicators of the effect of different land use. Some concentrations of all the OCPs registered had values above the limits for tap water., (© 2024. The Author(s).)

Background : The reconstruction of large breasts carries a heightened risk profile. While skin-reducing mastectomy (SRM) techniques facilitate the correction of breast ptosis, they are frequently associated with a high incidence of vascular complications. This study compares two SRM techniques-the horizontal incision and the classic inverted T incision-by examining their clinical and surgical outcomes. Methods : We retrospectively analyzed data from 24 patients (30 breasts) who underwent SRM with immediate prosthetic reconstruction between 2019 and 2023 at the European Institute of Oncology in Milan, Italy. Our comparison focused on breast aesthetic outcome, reconstruction quality, complication rates (early and late), and patient satisfaction, utilizing the BREAST-Q questionnaire to gauge the latter. Results : Among the 24 patients included in the study, 16 (20 breasts) were treated with the inverted T technique, and 8 (10 breasts) with the horizontal incision approach. A higher overall complication rate was observed with the inverted T technique compared to the horizontal method, with early complications outnumbering late ones. The most common issues were recurrent seroma and skin necrosis leading to implant exposure. Notably, there were no cases of implant infection. Although the horizontal incision technique achieved slightly higher patient satisfaction scores, the difference was not statistically significant. Discussion : The inverted T and horizontal incision techniques each have unique benefits and drawbacks. Our findings indicate enhanced patient satisfaction and reduced complication rates with the horizontal incision technique. The selection of the technique should be customized based on the patient's individual risk factors, tissue quality, and preferences.

Introduction: Diagnosis, outcomes, and costs of care associated with bowel dysfunction after proctectomy for cancer remain underexplored in population-based studies. The lack of administrative coding for bowel dysfunction or low anterior resection syndrome has historically limited secondary data set outcomes analysis. The purpose of this study was to identify a bowel dysfunction phenotype in administrative claims data and characterize its prevalence, predictive factors, and costs., Materials and Methods: Patients were identified with employer-sponsored commercial insurance (MarketScan research databases) undergoing proctectomy for cancer for a retrospective cohort study. Bowel dysfunction was defined as any patient with diagnostic codes for diarrhea, constipation, incontinence, pelvic floor diagnostic testing, or rehabilitative procedures that occurred in the 18 mo to follow surgery. We performed Poisson regression to identify statistically significant covariates of bowel dysfunction occurrence following low anterior resection. A secondary comparative analysis was also performed of total costs of healthcare utilization following gastrointestinal continuity., Results: 6426 proctectomy patients were identified, out of which 2131 had surgery for cancer. 847 patients undergoing proctectomy for cancer (39.7%) experienced bowel dysfunction during 18 mo of follow-up. The most common diagnoses were constipation (53.5%) and diarrhea (40.3%). Diagnostic procedures and rehabilitative procedures were performed in only 29.8% of those with symptoms. Neoadjuvant chemotherapy administration with radiation (incidence rate ratio = 1.23, 95% CI: 1.01-1.51) and without (incidence rate ratio = 1.20, 95% CI: 1.01-1.42) remained associated with postoperative bowel dysfunction when controlling for other factors. Chemoradiation therapy alone was not associated with bowel dysfunction. The median total follow-up costs with bowel dysfunction were $30,769 greater (P < 0.001)., Conclusions: More than one-third of patients have symptomatic bowel dysfunction within 18 mo after restored continuity, with multiagent chemotherapy being the strongest independent predictor. Bowel dysfunction is associated with more than twice healthcare costs postop., (Published by Elsevier Inc.)

This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration. To interrogate the mechanistic role of DEK in B-cell lymphoma, we generated a DEK knockout cell line model, which demonstrated DEK depletion caused reduced proliferation and altered expression of key cell cycle and apoptosis-related proteins, including Bcl-2, Bcl-xL, and p53. Notably, DEK depleted cells showed increased sensitivity to apoptosis-inducing agents, including venetoclax and staurosporine, which underscores the therapeutic potential of targeting DEK in B-cell lymphomas. Overall, our study contributes to a better understanding of DEK's role as an oncoprotein in B-cell lymphomas, highlighting its potential as both a promising therapeutic target and a novel biomarker for aggressive LGBCL. Further research elucidating the molecular mechanisms underlying DEK-mediated tumorigenesis could pave the way for improved treatment strategies and better clinical outcomes for patients with B-cell lymphoma., (© 2024. The Author(s).)

Objective: Myelomeningocele (MMC) is a lifelong condition requiring complex multidisciplinary management. Using the National Spina Bifida Patient Registry (NSBPR), the authors tested the association between sociodemographic variables and odds of undergoing neurosurgical procedures., Methods: The authors extracted sociodemographic, clinical, and neurosurgical procedure data on participants with MMC aged ≥ 1 year who visited an NSBPR clinic between 2009 and 2020. The zip code of the participant's residence at the time of the last spina bifida clinic visit was linked to the Distressed Communities Index (DCI) tier. Multivariate models were built to identify factors associated with undergoing CSF diversion, shunt revision, tethered cord release (TCR), and Chiari decompression., Results: There were 7924 participants with a median visit age of 13 years (IQR 7-20 years); 49.1% were male, 30.2% were non-Hispanic Black or Hispanic, 54.5% had public/supplemental insurance, and 16.9% were from distressed communities. CSF diversion, shunt revision, TCR, and Chiari decompression were performed in 81.8%, 47.7%, 22.9%, and 8.7% of participants, respectively. In multivariate analyses controlling for age, sex, insurance, DCI tier, lesion level, and surgical closure timing, Hispanic individuals were less likely than their non-Hispanic White counterparts to undergo shunt revision (p = 0.013). Non-Hispanic Black and Hispanic individuals were less likely to undergo TCR (p < 0.001 each) or Chiari decompression (p < 0.001 each). Compared with privately insured individuals, publicly insured individuals were more likely to undergo CSF diversion (p = 0.031). Those in distressed communities had increased odds of undergoing CSF diversion (p = 0.004) than those in prosperous communities., Conclusions: Among individuals with MMC participating in the NSBPR, there were differences in receiving neurosurgical procedures by race/ethnicity, insurance type, and DCI tier. Additional prospective studies are necessary to elucidate the reasons for these variations and their impact on long-term outcomes for this patient population in order to created targeted interventions.

Background: We examined national patterns of care and perioperative outcomes for women after mastectomy, comparing home recovery (HR) with hospital admission., Patients and Methods: Using Martketscan data (2017-2019), women ≥ 18 years old who underwent mastectomy ± reconstruction were identified and classified as either home recovery (same calendar day discharge) or hospital admission (stays > 1 calendar day). Comorbidities and receipt of chemo/immunotherapy 6 months prior to surgery and post-surgical 30-day complications were measured. Logistic regression calculated the odds of any complication by encounter type, adjusting for age, accompanying lymph node (LN) procedure, reconstruction, neoadjuvant chemo- and/or immunotherapy, and select comorbidities., Results: Of 11,789 mastectomy encounters (N = 11,659 women), 4751 (40%) cases utilized HR while 7038 (60%) had hospital admission. HR patients were older (53.6 years old vs. 51.8 years old) with lower rates of reconstruction (60.2 vs. 74.5%, p < 0.001). Rates of neoadjuvant chemotherapy (19.6 vs. 20.9%, p = 0.099) and immunotherapy (3.6 vs. 3.9%, p = 0.445) were similar between groups. Complication rates were lower among HR patients with fewer postoperative hematomas (0.6 vs. 1.3%, p < 0.001) and decreased wound complications (8.5 vs. 9.8%, p = 0.019). In a multivariable analysis, the odds of any complication were approximately 20% lower for HR patients compared with admission patients (aOR 0.81, 95% CI 0.72-0.91, p < 0.001). Unplanned emergency room visits were similar between groups (6.7 vs. 7.2%, p = 0.374); yet fewer hospital re-admissions (2.5 vs. 3.5%, p = 0.003) occurred in women recovering at home., Conclusion: HR is a safe option compared with in-hospital admission for clinically appropriate women after mastectomy as they are less likely to experience postoperative complications, emergency department (ED) visits, or hospitalization., (© 2024. Society of Surgical Oncology.)

The widespread use of potent androgen receptor signaling inhibitors (ARSIs) has led to an increasing emergence of AR-independent castration-resistant prostate cancer (CRPC), typically driven by loss of AR expression, lineage plasticity, and transformation to prostate cancers (PCs) that exhibit phenotypes of neuroendocrine or basal-like cells. The anti-apoptotic protein BCL2 is upregulated in neuroendocrine cancers and may be a therapeutic target for this aggressive PC disease subset. There is an unmet clinical need, therefore, to clinically characterize BCL2 expression in metastatic CRPC (mCRPC), determine its association with AR expression, uncover its mechanisms of regulation, and evaluate BCL2 as a therapeutic target and/or biomarker with clinical utility. Here, using multiple PC biopsy cohorts and models, we demonstrate that BCL2 expression is enriched in AR-negative mCRPC, associating with shorter overall survival and resistance to ARSIs. Moreover, high BCL2 expression associates with lineage plasticity features and neuroendocrine marker positivity. We provide evidence that BCL2 expression is regulated by DNA methylation, associated with epithelial-mesenchymal transition, and increased by the neuronal transcription factor ASCL1. Finally, BCL2 inhibition had antitumor activity in some, but not all, BCL2-positive PC models, highlighting the need for combination strategies to enhance tumor cell apoptosis and enrich response.

The DEK chromatin remodeling protein was previously shown to confer oncogenic phenotypes to human and mouse mammary epithelial cells using in vitro and knockout mouse models. However, its functional role in normal mammary gland epithelium remained unexplored. We developed two novel mouse models to study the role of Dek in normal mammary gland biology in vivo . Mammary gland-specific Dek over-expression in mice resulted in hyperproliferation of cells that visually resembled alveolar cells, and a transcriptional profile that indicated increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited an alveologenesis or lactation defect, resulting in dramatically reduced pup survival. Analysis of previously published single-cell RNA-sequencing of mouse mammary glands revealed that Dek is most highly expressed in mammary stem cells and alveolar progenitor cells, and to a lesser extent in basal epithelial cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, upregulating the levels of histone H3 trimethylation on lysine 27 (H3K27me3) to control gene transcription. Combined, this work indicates that Dek promotes proliferation of mammary epithelial cells via cell cycle deregulation. Furthermore, we report a novel function for Dek in alveologenesis and histone H3 K27 trimethylation.

Introduction: The immune system is an intricate network of cellular components that safeguards against pathogens and aberrant cells, with CD4+ T cells playing a central role in this process. Human space travel presents unique health challenges, such as heavy ion ionizing radiation, microgravity, and psychological stress, which can collectively impede immune function. The aim of this research was to examine the consequences of simulated space stressors on CD4+ T cell activation, cytokine production, and gene expression., Methods: CD4+ T cells were obtained from healthy individuals and subjected to Fe ion particle radiation, Photon irradiation, simulated microgravity, and hydrocortisone, either individually or in different combinations. Cytokine levels for Th1 and Th2 cells were determined using multiplex Luminex assays, and RNA sequencing was used to investigate gene expression patterns and identify essential genes and pathways impacted by these stressors., Results: Simulated microgravity exposure resulted in an apparent Th1 to Th2 shift, evidenced on the level of cytokine secretion as well as altered gene expression. RNA sequencing analysis showed that several gene pathways were altered, particularly in response to Fe ions irradiation and simulated microgravity exposures. Individually, each space stressor caused differential gene expression, while the combination of stressors revealed complex interactions., Discussion: The research findings underscore the substantial influence of the space exposome on immune function, particularly in the regulation of T cell responses. Future work should focus expanding the limited knowledge in this field. Comprehending these modifications will be essential for devising effective strategies to safeguard the health of astronauts during extended space missions., Conclusion: The effects of simulated space stressors on CD4+ T cell function are substantial, implying that space travel poses a potential threat to immune health. Additional research is necessary to investigate the intricate relationship between space stressors and to develop effective countermeasures to mitigate these consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Miranda, Vermeesen, Janssen, Rehnberg, Etlioglu, Baatout, Tabury and Baselet.)

Obesity is an alarming worldwide public health issue and is defined as a body mass index (BMI) of 30kg/m 2 or more. It is considered as a risk factor for first thrombotic event and is associated with a significant risk of recurrence. Consequently, obese patients are often treated by anticoagulant therapy but data from randomised control trial are scarce. We will review in this narrative review the state of the art of the prescription of anticoagulant for the prevention and treatment of venous thromboembolism (VTE) in obese patients., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Acute bronchiolitis is a common reason for admission to the pediatric emergency department. Evidence has shown that most interventions do not change the natural course of the disease., Material and Methods: This study aimed to evaluate the economic impact of the non-compliance with the acute bronchiolitis Portuguese national guideline. A retrospective study of pediatric emergency episodes of a Portuguese hospital that had a diagnosis of acute bronchiolitis during 2019, was conducted., Results: The sample included 344 emergency episodes. Non-compliance with the guideline occurred in 71.8% of the episodes, mostly due to unjustified treatment. Following guideline in the studied hospital for one year would have resulted in an estimated overall 76.6% cost reduction, with a reduction in mean direct costs per patient of 14.93 €, corresponding to a medium saving of 3.89 € for each patient and a reduction of 11.03 € for the Portuguese National Health Service. Analyzing the unjustified mean direct costs, of these 2.97 € were related to inpatient diagnostic tests and therapeutic and the remaining 11.96 € were related to outpatient therapy. Mean direct costs imputed to the patient for outpatient treatment represented only 3.31 €, therefore most of mean direct costs is paid by the National Health Service., Conclusions: Compliance with guideline would allow the reduction of total estimated costs by about 76.6%, representing a waste of resources, without compromising the quality of care provided. Most of the cost associated with non-compliance with the guideline is justified by outpatient therapy, 67% of which was paid by the National Health Service., (Copyright © 2024 FECA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The risk of death due to tuberculosis (TB) in Brazil is high and strongly related to living conditions (LC). However, epidemiological studies investigating changes in LC and their impact on TB are lacking., Objectives: To evaluate the impact of LC on TB mortality in Brazil., Design and Setting: This ecological study, using panel data on spatial and temporal aggregates, was conducted in 1,614 municipalities between 2002 and 2015., Methods: Data were collected from the Mortality Information System and the Brazilian Institute of Geography and Statistics. The proxy variable used for LC was the Urban Health Index (UHI). Negative binomial regression models were used to estimate the effect of the UHI on TB mortality rate. Attributable risk (AR) was used as an impact measure., Results: From 2002 to 2015, TB mortality rate decreased by 23.5%, and LC improved. The continuous model analysis resulted in an RR = 0.89 (95%CI = 0.82-0.96), so the AR was -12.3%. The categorized model showed an effect of 0.92 (95%CI = 0.83-0.95) in municipalities with intermediate LC and of 0.83 (95%CI = 0.82-0.91) in those with low LC, representing an AR for TB mortality of -8.7% and -20.5%, respectively., Conclusions: Improved LC impacted TB mortality, even when adjusted for other determinants. This impact was greater in the strata of low-LC municipalities.

Background: Around half of preterm births lack identifiable causes, indicating the need for further investigation to understand preterm birth risk factors. Existing studies on the intergenerational association of preterm birth showed inconsistency in effect size and direction., Objective: This systematic review and meta-analysis aimed to review existing studies and provide comprehensive evidence on the intergenerational association of preterm births., Search Strategy: We searched MEDLINE, Embase and Maternity and Infant Care databases, from the inception of each database to 04 April 2024., Selection Criteria: Eligibility criteria included studies that reported on women who had given birth and had recorded information about a family history of preterm birth in one or both of the child's biological parents., Data Collection and Analysis: Data were extracted by two independent reviewers. A random-effects model was used to compute pooled estimates using odds ratios., Main Results: Sixteen eligible studies with a total of 2 271 612 mothers were included. The findings indicated a 1.44 (OR = 1.44, 95% CI: 1.34, 1.54) fold increase in odds of giving preterm births among women who were born preterm. Additionally, having a sibling born preterm (OR = 1.53, 95% CI: 1.24, 1.87) and having a partner born preterm (OR = 1.12, 95% CI: 1.01, 1.25) were associated with increased likelihood of giving preterm births among women., Conclusion: The study revealed that women with a family history of preterm birth face an increased risk of giving preterm births. Screening pregnant women for a family history of preterm birth is essential, with those having a positive family history requiring closer follow-up., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Countries in the Americas play a vital role in global livestock and aquaculture production. With international trade of livestock and aquaculture products becoming an important source of income for countries, there has been an increased interest in using animal health economics for advocacy and allocation of resources. This article discusses the development of a new Collaborating Centre for the Economics of Animal Health and the applications of the Global Burden of Animal Diseases (GBADs) framework in the Americas region. Incentives for the increased use of economics in animal health decision-making and examples from the Americas region are examined. The article then discusses the newly formed World Organisation for Animal Health Collaborating Centre in the Americas region. Finally, it reviews two ongoing case studies that are implementing the GBADs framework in Peru and the United States of America.

Background: Endovascular aortic surgery is increasingly becoming the standard treatment. Percutaneous access preclosing systems appear to be effective and notably the Proglide (PG). We aimed to prospectively assess the clinical effectiveness of combining ultrasound-guided femoral puncture with ultrasound-guided PG deployment., Methods: Our single-center study consecutively included patients managed at a tertiary center from May to September 2023, undergoing endovascular aortic surgery. The placement of PG was performed under ultrasound guidance. Preoperative patient characteristics were evaluated using preoperative computed tomography scans. Clinical and technical success were defined, respectively, as the ability to achieve complete hemostasis confirmed by ultrasound 48 hr postprocedure and as the successful placement of a PG under ultrasound guidance contributing to final hemostasis., Results: Twenty patients were included over a 6-month period, totaling 34 common femoral arteries (CFAs). Fourteen were male, with an average age of 72.8 ± 8.2 years. Among the 34 CFA, CFA had diameter of 12.05 ± 2.4 mm and a depth of 38.0 ± 13.4 mm. The mean introducer sheath diameter was 6.2 ± 1.5 mm with a sheath to femoral artery ratio of 0.54 ± 0.18. Successful Proglide placement under ultrasound guidance was achieved in 100% of cases. No PG failure occurred. Clinical and technical success were, respectively, of 95% and 100%. One small pseudoaneurysm was observed at 48 hr treated medically. No CFA access reintervention was required., Conclusions: The technique of ultrasound-guided PG deployment in aortic surgery is a safe and effective method for achieving hemostasis. It effectively prevents PG failures at a lower cost., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Environmental enrichment is used to provide well-being to the animals, such as fish, in captive conditions, mimicking their natural habitat. It may influence fish behavior, physiology, and survival. In terms of reproduction, however, the relationship between environment enrichment and successful reproduction in captivity is still poorly explored in fish species. Aiming to understand any possible benefits of structural enrichment on fish reproduction, 10-days-hatched larvae of the twospot astyanax Astyanax bimaculatus were raised for 18 weeks in tanks with different elements of structural environmental enrichment (PVC pipes, stones, and artificial plants). In the 5th month of life, those animals were hormonally induced to reproduce to assess gamete formation and offspring quality. Animals raised in a sterile-reared environment (non-enriched) showed earlier spawning than the enriched one, presenting significant quantities of Postovulatory follicle complexes (POCs) and cells in atresia in female ovaries, indicating possible reproductive dysfunction or stress, as well as a greater quantity of empty testicular lumen in males, indicating great release of sperm. On the contrary, animals cultivated in enriched environments showed gonads filled with semen in males and vitellogenic oocytes in females. Furthermore, offspring from the sterile-reared group presented significant rates of larval abnormality compared to the enriched group. In conclusion, the results of this study show that environmental enrichment can interfere with the reproduction of fish in captivity, mainly by preventing early maturation of gametes, which can result in low-quality offspring and, consequently, low production of fish species., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) remains a pervasive clinical problem associated with significant morbidity and mortality. However, TBI remains clinically and biophysically ill-defined, and prognosis remains difficult even with the standardization of clinical guidelines and advent of multimodality monitoring. Here we leverage a unique data set from TBI patients implanted with either intracranial strip electrodes during craniotomy or quad-lumen intracranial bolts with depth electrodes as part of routine clinical practice. By extracting spectral profiles of this data, we found that the presence of narrow-band oscillatory activity in the beta band (12-30 Hz) closely corresponds with the neurological exam as quantified with the standard Glasgow Coma Scale (GCS). Further, beta oscillations were distributed over the cortical surface as traveling waves, and the evolution of these waves corresponded to recovery from coma, consistent with the putative role of waves in perception and cognitive activity. We consequently propose that beta oscillations and traveling waves are potential biomarkers of recovery from TBI. In a broader sense, our findings suggest that emergence from coma results from recovery of thalamo-cortical interactions that coordinate cortical beta rhythms., Competing Interests: Competing interests: the authors declare no competing interests.

Background: Functional capacity impairment is a crucial consequence of chronic obstructive pulmonary disease (COPD). Although it can be identified with simple tests, such as the sit-to-stand tests, its prevalence, relation with disease severity, and the characteristics of people presenting this impairment remain unknown., Objective: To explore the functional capacity of people with COPD., Methods: A cross-sectional study with people with COPD and age-/sex-matched healthy controls was conducted. Functional capacity was assessed with the 5-repetitions (5-STS) and the 1-minute (1-minSTS) sit-to-stand tests. People with COPD were grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications. Comparisons between people with COPD and healthy controls, and among GOLD groups were established. Associations between symptoms, muscle strength, quality of life, and measures of functional capacity were explored., Results: 302 people with COPD [79% male; mean (SD) 68 (10) years old] and 304 healthy controls [75% male; 66 (9) years old] were included. 23% of people with COPD presented impairment in the 5-STS and 33% in the 1-minSTS. People with COPD from all GOLD classifications presented significantly lower functional capacity than healthy controls (5-STS: COPD median [1st quartile; 3rd quartile] 8.4 [6.7; 10.6] versus healthy 7.4 [6.2; 9.3] s; 1-minSTS: COPD 27 [21; 35] vs healthy 35 [29; 43] reps). Correlations with symptoms, muscle strength, and quality of life were mostly weak (5-STS: r s [-0.34; 0.33]; 1-minSTS: r s [-0.47; 0.40])., Conclusion: People with COPD have decreased functional capacity independently of their GOLD classifications. The prevalence of functional impairment is 23-33%. Because impaired functional capacity is a treatable trait not accurately reflected by other outcomes, comprehensive assessment and management is needed., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: PTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel., Methods: This double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥ 18 years with progressing mCRPC and performance status 0-2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160 mg orally, once daily) with capivasertib (400 mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥ 50 % PSA decrease from baseline, or circulating tumor cell count conversion (from ≥ 5 at baseline to < 5 cells/7.5 mL). Subgroup analyses by PTEN IHC status were pre-planned., Results: Overall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1 %) enzalutamide/capivasertib and 9/48 (18.8 %) enzalutamide/placebo (absolute difference 0.4 % 90 %CI -12.8 to 13.6, p = 0.58), with similar results in the PTEN IHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTEN IHC loss (10.1 months [95 %CI: 4.6-13.9] vs 14.8 months [95 %CI: 10.8-18]; p = 0.02). Most common treatment-emergent grade ≥ 3 adverse events for the combination were diarrhea (13 % vs 2 %) and fatigue (10 % vs 6 %)., Conclusions: Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JdB reports advisory board fees from many companies including Acai Therapeutics, Amgen, Astra Zeneca, Astellas, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Crescendo, Daiichi, Dark Blue Therapeutics, Eisai, Genentech/Roche, Genmab, GSK, Harpoon, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Menarini/Silicon Biosystems, MetaCurUm, Myricx, Novartis, Nurix Therapeutics, Oncternal, Orion, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Takeda, Tango Therapeutics, Terumo, Vertex Pharmaceuticals. He is an employee of The ICR, which have received funding or other support for his research work from Acai Therapeutics, Amgen, AstraZeneca, Astellas, Bayer, Cellcentric, Crescendo, Daiichi, Genentech, Genmab, GSK, Harpoon, Immunic Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Menarini/Silicon Biosystems, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal, Orion, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals. The ICR have a commercial interest in abiraterone, PARP inhibition in DNA repair defective cancers and PI3K/AKT pathway inhibitors (no personal income). JDB was named as an inventor, with no financial interest for patent 8,822,438, submitted by Janssen that covers the use of abiraterone acetate with corticosteroids. EH reports that their institution has received an Investigator Initiated Research grant (IIR) from AstraZeneca for the central coordination of the trial. EH reports grants received by their institution as contribution to support central trial costs for non-commercial trials from Accuray, Varian Medical Systems, AstraZeneca, Janssen-Cilag, Bayer, Roche Products, and Merck Sharp and Dohm. SJ reports advisory boards and speaker fees received from AAA/Novartis, Accord, Astellas, Astra Zeneca, Bayer, Boston Scientific, Janssen and Pfizer, as well as consultancy fees received from Boston Scientific and BXT Nanotherapy. SJ also reports conferences travel received from Bayer and Janssen. AJB reports honoraria from Janssen-Cilag, consulting or advisory roles from Roche, Astellas Medivation, Janssen Oncology, AstraZeneca, Sanofi, Bayer Schering Pharma, Bristol-Myers-Squib, Merck Serono and Pfizer. AJB also reports speakers’ fees received from Bayer, Janssen Oncology and Pfizer. RJ reports honoraria from Astellas Pharma, Janssen, AstraZeneca, MSD Oncology, Bristol Myers Squibb, Pfizer, Novartis, Ipsen, Bayer, Roche/Genentech, Merck Serono, Eisai, WebMD, Advanced Accelerator Applications/Novartis and Elsevier. RJ also reports speakers’ fees received from Merck Serono, Pfizer, Janssen, Astellas Pharma, MSD Oncology, AstraZeneca, Ipsen, Bristol Myers Squibb/Celgene and Bayer. RJ also reports research Funding received from Roche (Inst), Astellas Pharma (Inst), AstraZeneca (Inst), Exelixis (Inst), Clovis Oncology (Inst) and Bayer (Inst), as well as travel, accommodations and expenses received from Ipsen, Bayer, Janssen, Astellas Pharma, MSD, Merck Serono and Pfizer. PR, NP, LF, AE, SM, PF, JG, JN, RR, BG, DR, IF, SC, CB, AF, MC, SC, ZM, CR, UMC, PH, PS, EC and DML have no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sex determination in monomorphic birds is a precondition for captive breeding programs and management and conservation strategies for threatened species. Most species of the order Psittaciformes often present complications since these birds lack external sexual phenotypic traits, making it impossible to differentiate males and females. In the present study, we used molecular techniques to determine the sex of 31 individuals belonging to nine species of the order Psittaciformes kept under human care at the Akumal Monkey Sanctuary & Rescued Animals in Quintana Roo, Mexico. This is a useful and low-cost methodology based on the analysis of the conserved region of the CHD1 gene, which was amplified by PCR with two sets of primers: P8/P2 and 2550F/2718 R. All individuals were successfully sexed with the first set of primers, while only 28 out of 31 samples (90%) could be amplified with the second set. Out of the 31 individuals analyzed, fifteen are female, and seventeen are male. This information represents a handy tool for adequately managing birds under human care, resulting in their reproduction and eventual reintegration into their natural habitat.

BACKGROUNDClinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome, and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.METHODSWhole tumor biopsies from multiple cohorts of patients with advanced prostate cancer were interrogated using whole-exome sequencing (WES), RNA-Seq (bulk and single nucleus), and IHC for RNASEH2B and RB1. Biopsies from patients treated with olaparib in the TOPARP-A and TOPARP-B clinical trials were used to evaluate RNASEH2B clonal selection during olaparib treatment.RESULTSShallow codeletion of RNASEH2B and adjacent RB1 - colocated at chromosome 13q14 - was common, deep codeletion infrequent, and gene loss associated with lower mRNA expression. In castration-resistant prostate cancer (CRPC) biopsies, RNASEH2B and RB1 mRNA expression correlated, but single nucleus RNA-Seq indicated discordant loss of expression. IHC studies showed that loss of the 2 proteins often occurred independently, arguably due to stochastic second allele loss. Pre- and posttreatment metastatic CRPC (mCRPC) biopsy studies from BRCA1/2 WT tumors, treated on the TOPARP phase II trial, indicated that olaparib eradicated RNASEH2B-loss tumor subclones.CONCLUSIONPARP inhibition may benefit men suffering from mCRPC by eradicating tumor subclones with RNASEH2B loss.TRIAL REGISTRATIONClinicaltrials.gov NCT01682772.FUNDINGAstraZeneca; Cancer Research UK; Medical Research Council; Cancer Research UK; Prostate Cancer UK; Movember Foundation; Prostate Cancer Foundation.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BCL-2-associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC. In addition, interrogation of geometric and physiochemical properties of the BAG domain of BAG-1 isoforms identifies it to be a tractable but challenging drug target. Furthermore, through BAG-1 isoform mouse knockout studies, we confirm that BAG-1 isoforms regulate hormone physiology and that therapies targeting the BAG domain will be associated with limited "on-target" toxicity. Importantly, the postulated inhibitor of BAG-1 isoforms, Thio-2, suppressed AR signaling and other important pathways implicated in the development and progression of CRPC to reduce the growth of treatment-resistant prostate cancer cell lines and patient-derived models. However, the mechanism by which Thio-2 elicits the observed phenotype needs further elucidation as the genomic abrogation of BAG-1 isoforms was unable to recapitulate the Thio-2-mediated phenotype. Overall, these data support the interrogation of related compounds with improved drug-like properties as a novel therapeutic approach in CRPC, and further highlight the clinical potential of treatments that block persistent AR signaling which are currently undergoing clinical evaluation in CRPC., (©2024 The Authors; Published by the American Association for Cancer Research.)

Dilated cardiomyopathy (DCM) is a condition characterized by impaired cardiac function, due to myocardial hypo-contractility, and is associated with point mutations in β-cardiac myosin, the molecular motor that powers cardiac contraction. Myocardial function can be modulated through sequestration of myosin motors into an auto-inhibited "super-relaxed" state (SRX), which may be further stabilized by a structural state known as the "interacting heads motif" (IHM). Here, we sought to determine whether hypo-contractility of DCM myocardium results from reduced function of individual myosin molecules or from decreased myosin availability to interact with actin due to increased IHM/SRX stabilization. We used an established DCM myosin mutation, E525K, and characterized the biochemical and mechanical activity of wild-type and mutant human β-cardiac myosin constructs that differed in the length of their coiled-coil tail, which dictates their ability to form the IHM/SRX state. We found that short-tailed myosin constructs exhibited low IHM/SRX content, elevated actin-activated ATPase activity, and fast velocities in unloaded motility assays. Conversely, longer-tailed constructs exhibited higher IHM/SRX content and reduced actomyosin ATPase and velocity. Our modeling suggests that reduced velocities may be attributed to IHM/SRX-dependent sequestration of myosin heads. Interestingly, longer-tailed E525K mutants showed no apparent impact on velocity or actomyosin ATPase at low ionic strength but stabilized IHM/SRX state at higher ionic strength. Therefore, the hypo-contractility observed in DCM may be attributable to reduced myosin head availability caused by enhanced IHM/SRX stability in E525K mutants., (© 2024 Duno-Miranda et al.)

Background: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood., Methods: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment., Results: Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1β production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1β and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1β, TNF-α, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth., Conclusions: Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes., (© 2024. The Author(s).)

Background: The morbidity and mortality rates from neonatal sepsis remain high. However, there is limited information about the microbial pattern of neonatal sepsis in Indonesia. Microbial patterns can give an overview of the hygiene of an environment and act as a determinant for choosing definitive antibiotic treatment in neonatal sepsis patients. The organisms that cause neonatal sepsis differ from unit to unit and from time to time within the same unit., Objectives: This study is aimed at discovering the microbial pattern of neonatal sepsis in the Neonatal Intensive Care Unit (NICU), dr. Ramelan Navy Central Hospital, in 2021-2022., Methods: This is a retrospective, cross-sectional study that takes secondary data from the NICU and clinical microbiology department of dr. Ramelan Navy Central Hospital. Data that met the inclusion and exclusion criteria available between January 1, 2021, and December 31, 2022, were collected. Patients whose blood cultures were positive for bacterial growth and diagnosed with sepsis were selected as the study sample., Results: Out of 174 samples, 93 (53.4%) were found positive for bacterial infection and diagnosed as neonatal sepsis. Gram-negative isolates (96.8%) were predominant. Sixty-point-two percent of Klebsiella pneumoniae XDR , 19.4% of Klebsiella pneumoniae ESBL , and 8.6% of Burkholderia cepacia XDR were identified. The gram-positive isolates found in this study were only 3 samples (3.2%). Two-point-one percent of MRSA and 1.1% of Staphylococcus haemolyticus MDR were identified., Conclusion: The most common microorganisms causing neonatal sepsis in our NICU were gram-negative bacteria, particularly Klebsiella pneumoniae XDR . Following the recommended infection control procedures, practicing good hand hygiene, and having access to basic supplies and equipment are important to prevent and reduce the incidence of sepsis., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2024 Stefani Miranda et al.)

Apples ( Malus × domestica Borkh.) and pears ( Pyrus communis L.) are valuable crops closely related within the Rosaceae family with reported nutraceutical properties derived from secondary metabolites including phloridzin and arbutin, which are distinctive phenolic metabolites characterizing apples and pears, respectively. Here, we generated a de novo transcriptome assembly of an intergeneric hybrid between apple and pear, accumulating intermediate levels of phloridzin and arbutin. Combining RNA-seq, in silico functional annotation prediction, targeted gene expression analysis, and expression-metabolite correlations, we identified candidate genes for functional characterization, resulting in the identification of active arbutin synthases in the hybrid and parental genotypes. Despite exhibiting an active arbutin synthase in vitro , the natural lack of arbutin in apples is reasoned by the absence of the substrate and broad substrate specificity. Altogether, our study serves as the basis for future assessment of potential physiological roles of identified genes by genome editing of hybrids and pears.

Resistance to available antibiotics poses a growing challenge to modern medicine, as this often disallows infections to be controlled. This problem can only be alleviated by the development of new drugs. Nisin, a natural lantibiotic with broad antimicrobial activity, has shown promise as a potential candidate for combating antibiotic-resistant bacteria. However, nisin is poorly soluble and barely stable at physiological pH, which despite attempts to address these issues through mutant design has restricted its use as an antibacterial drug. Therefore, gaining a deeper understanding of the antimicrobial effectiveness, which relies in part on its ability to form pores, is crucial for finding innovative ways to manage infections caused by resistant bacteria. Using large-scale molecular dynamics simulations, we find that the bacterial membrane-specific lipid II increases the stability of pores formed by nisin and that the interplay of nisin and lipid II reduces the overall integrity of bacterial membranes by changing the local thickness and viscosity.

Background: Identifying risk factors for early child physical abuse (CPA) is crucial for understanding its mechanisms and defining effective preventive interventions. We aimed to identify maternal, prenatal and postnatal factors associated with early CPA., Methods: This cohort study was based on comprehensive data from the Mother-Child EPI-MERES nationwide register and included all infants born alive in France between 2010 and 2019. Factors associated with early CPA (before age 1) were identified with a multilevel Cox regression model with random intercepts at the regional level., Findings: Among the 6,897,384 included infants, 2994 (40/100,000) had a diagnosis of early CPA, at a median age of 4 months. Independent factors most strongly associated with early CPA were maternal low financial resources (adjusted hazard ratio [aHR] 1.91; 95% confidence interval [95% CI] 1.67-2.18), maternal age <20 years versus 35-40 years (aHR 7.06; 95% CI 6.00-8.31), maternal alcohol use disorder (aHR 1.85; 95% CI 1.48-2.31), opioid use disorder (aHR 1.90; 95% CI 1.41-2.56), intimate partner violence (aHR 3.33; 95% CI 2.76-4.01), diagnosis of a chronic mental disorder (aHR 1.50; 95% CI 1.14-1.97) or somatic disorder (aHR 1.55; 95% CI 1.32-1.83), hospitalisation for a mental disorder (aHR 1.88; 95% CI 1.49-2.36), very preterm birth (aHR 2.15; 95% CI 1.68-2.75), and diagnosis of a chronic severe neurocognitive disorder in the infant (aHR 14.37; 95% CI 11.85-17.44)., Interpretation: Independent risk factors of early CPA identified at the national level in France may help in understanding CPA mechanisms and developing effective prevention programs including risk-stratification tools to optimise the allocation of parenting interventions to parents who could most benefit from them., Funding: Ile-de-France regional council, L'Oréal-UNESCO For Women In Science France Young Talent Award, French National Observatory for Child Protection [ONPE], French Association of Ambulatory Paediatrics [AFPA], HUGO university hospitals network, Mustela Foundation and Sauver la Vie prizes., Competing Interests: FB, EL and MC received external funding for this study (Ile-de-France regional council; L'Oréal-UNESCO For Women in Science France Young Talent Award; French National Observatory for Child Protection [ONPE], French Association of Ambulatory Paediatrics [AFPA], HUGO university hospitals network; Mustela Foundation and Sauver la Vie prizes). All authors have nothing to disclose, no patents, products in development, or marketed products to declare., (© 2024 The Authors.)

Background: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated., Methods: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice., Results: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice., Conclusions: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage., (© 2024. The Author(s).)

Without the protective shielding of Earth's atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities., (© 2024. The Author(s).)

Background: Traumatic brain injury patients who require neurosurgical intervention are at the highest risk of worsening intracranial hemorrhage. This subgroup of patients has frequently been excluded from prior research regarding the timing of venous thromboembolism chemoprophylaxis. This study aims to assess the efficacy and safety of early venous thromboembolism chemoprophylaxis in patients with traumatic brain injuries requiring neurosurgical interventions., Methods: This is a single-center retrospective review (2016-2020) of traumatic brain injury patients requiring neurosurgical intervention admitted to a level I trauma center. Interventions included intracranial pressure monitoring, subdural drain, external ventricular drain, craniotomy, and craniectomy. Exclusion criteria included neurosurgical intervention after chemoprophylaxis initiation, death within 5 days of admission, and absence of chemoprophylaxis. The total population was stratified into Early (≤72 hours of intervention) versus Late (>72 hours after intervention) chemoprophylaxis initiation., Results: A total of 351 patients met the inclusion criteria, of whom 204 (58%) had early chemoprophylaxis initiation. Overall, there were no significant differences in baseline and admission characteristics between cohorts. The Early chemoprophylaxis cohort had a statistically significant lower venous thromboembolism rate (5% vs 13%, P < .001) with no increased risk of worsening intracranial hemorrhage (10% vs 13%, P = .44) or neurosurgical reintervention (8% vs 10%, P = .7). On subgroup analysis, a total of 169 patients required either a craniotomy or a craniectomy before chemoprophylaxis. The Early chemoprophylaxis cohort had statistically significant lower venous thromboembolism rates (2% vs 11%, P < .001) with no increase in intracranial hemorrhage (8% vs 11%, P = .6) or repeat neurosurgical intervention (8% vs 10%, P = .77)., Conclusion: Venous thromboembolism prophylaxis initiation within 72 hours of neurosurgical intervention is safe and effective. Further prospective research is warranted to validate the results of this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Patients' perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as "adequate" or "inadequate" cleansing before colonoscopy., Patients and Methods: Patients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process. The images were categorized as adequate or inadequate cleansing based on a predefined 4-picture quality scale. A total of 1203 images were collected from 660 patients. The initial dataset (799 images), was split into a training set (80%) and a validation set (20%). The second dataset (404 images) was used to develop a second test of the CNN accuracy. Afterward, CNN prediction was prospectively compared with the Boston Bowel Preparation Scale (BBPS) in 200 additional patients who provided a picture of their last rectal effluent., Results: On the initial dataset, a global accuracy of 97.49%, a sensitivity of 98.17% and a specificity of 96.66% were obtained using the CNN model. On the second dataset, an accuracy of 95%, a sensitivity of 99.60% and a specificity of 87.41% were obtained. The results from the CNN model were significantly associated with those from the BBPS (P<0.001), and 77.78% of the patients with poor bowel preparation were correctly classified., Conclusion: The designed CNN is capable of classifying "adequate cleansing" and "inadequate cleansing" images with high accuracy., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Childhood obesity is a major public health challenge. Previous research has identified the impact of school-based interventions for preventing and treating obesity; we hypothesized that when curricular changes are integrated, results could be exponentiated. This study aimed to systematically review and conduct a meta-analysis of the published literature analyzing information about school-based interventions inserted in the curriculum. The Cochrane Handbook methodology was followed. An electronic search was conducted in five databases, with a specific design strategy per database. Randomized controlled trials or quasi-experimental studies of children with nutrition and physical activity (PA) interventions inserted into the school curricula were included. The risk of bias was assessed with the Risk of Bias tool. The mean differences were pooled using a fixed-effects model for the meta-analysis. The certainty of the evidence was evaluated according to the guidelines of the Grading of the Recommendations, Assessment, Development, and Evaluations working group (Protocol ID: CRD42021270557). After the screening and selection process, 12 studies were included. The interventions identified, based on the school curricula, include classroom activities and homework, among others. A meta-analysis with five intervention groups presented an overall mean difference of -0.14 body mass index (BMI) Z-score (95% CI: -0.25, -0.03) after this intervention with high certainty of the evidence. This systematic review and meta-analysis suggest that nutrition and PA lessons inserted into the curricula and supported with additional activities (i.e. homework, workshops, etc.) could increase nutrition knowledge and improve attitudes toward fruit, vegetables, and water consumption, and BMI Z-score reduction., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Bacterial organisms causing neonatal sepsis have developed increased resistance to commonly used antibiotics. Antimicrobial resistance is a major global health problem. The spread of Multidrug-Resistant Organisms (MDROs) is associated with higher morbidity and mortality rates. This study aimed to determine the risk factors for developing MDRO neonatal sepsis in the Neonatal Intensive Care Unit (NICU), dr. Ramelan Navy Central Hospital, in 2020-2022., Methods: A cross-sectional study was performed on 113 eligible neonates. Patients whose blood cultures were positive for bacterial growth and diagnosed with sepsis were selected as the study sample. Univariate and multivariate analysis with multiple logistic regression were performed to find the associated risk factors for developing multidrug-resistant organism neonatal sepsis. A p-value of < 0.05 was considered significant., Results: Multidrug-resistant organisms were the predominant aetiology of neonatal sepsis (91/113, 80.5%). The significant risk factors for developing MDRO neonatal sepsis were lower birth weight (OR: 1.607, 95% CI: 1.003 - 2.576, p-value: 0.049), history of premature rupture of the membrane (ProM) ≥ 18 (OR: 3.333, 95% CI: 2.047 - 5.428, p-value < 0.001), meconium-stained amniotic fluid (OR: 2.37, 95% CI: 1.512 - 3.717, p-value < 0.001), longer hospital stays (OR: 5.067, 95% CI: 2.912 - 8.815, p-value < 0.001), lower Apgar scores (OR: 2.25, 95% CI: 1.442 - 3.512, p-value < 0.001), and the use of respiratory support devices, such as invasive ventilation (OR: 2.687, 95% CI: 1.514 - 4.771, p-value < 0.001), and non-invasive ventilation (OR: 2, 95% CI: 1.097 - 3.645, p-value: 0.024)., Conclusions: Our study determined various risk factors for multidrug-resistance organism neonatal sepsis and underscored the need to improve infection control practices to reduce the existing burden of drug-resistant sepsis. Low-birth-weight, a maternal history of premature rupture of the membrane lasting more than 18 hours, meconium-stained amniotic fluid, longer hospital stays, a low Apgar score, and the use of ventilators were the risk factors for developing drug-resistant neonatal sepsis., (© 2024. The Author(s).)

Climate change and rapid adaption of invasive pathogens pose a constant pressure on the fruit industry to develop improved varieties. Aiming to accelerate the development of better-adapted cultivars, new breeding techniques have emerged as a promising alternative to meet the demand of a growing global population. Accelerated breeding, cisgenesis, and CRISPR/Cas genome editing hold significant potential for crop trait improvement and have proven to be useful in several plant species. This review focuses on the successful application of these technologies in fruit trees to confer pathogen resistance and tolerance to abiotic stress and improve quality traits. In addition, we review the optimization and diversification of CRISPR/Cas genome editing tools applied to fruit trees, such as multiplexing, CRISPR/Cas-mediated base editing and site-specific recombination systems. Advances in protoplast regeneration and delivery techniques, including the use of nanoparticles and viral-derived replicons, are described for the obtention of exogenous DNA-free fruit tree species. The regulatory landscape and broader social acceptability for cisgenesis and CRISPR/Cas genome editing are also discussed. Altogether, this review provides an overview of the versatility of applications for fruit crop improvement, as well as current challenges that deserve attention for further optimization and potential implementation of new breeding techniques., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Human type A rotavirus (RV-A) is world-recognized as the major pathogen causing viral gastroenteritis in children under 5 years of age. The literature indicates a substantial increase in the diversity of rotavirus strains across continents, especially in Africa, which can pose significant challenges including an increase of disease burden and a reduction of vaccines' effectiveness. However, few studies have mapped the variety of circulating virus strains in different regions, which may hamper decisions on epidemiological surveillance and preventive public health measures. Thus, our aim was to compile the most updated available evidence on the genetic profile of RV-A among children in Africa and determine the prevalence of different genotypes according to the geographical regions by means of a broad systematic review. Systematic searches were performed in PubMed, Scopus, Web of Science, and Scielo without language, time limits, or geographical restrictions within the African continent. We selected full-text peer-reviewed articles assessing the genetic profile (i.e., genotyping) of RV-A in children up to 5 years old in Africa. Overall, 682 records were retrieved, resulting in 75 studies included for evidence synthesis. These studies were published between 1999 and 2022, were conducted in 28 countries from the five African regions, and 48% of the studies were carried out for 24 months or more. Most studies (n = 55; 73.3%) evaluated RV-A cases before the introduction of the vaccines, while around 20% of studies (n = 13) presented data after the vaccine approval in each country. Only seven (9.3%) studies compared evidence from both periods (pre- and post-vaccine introduction). Genotyping methods to assess RV-A varied between RT-PCR, nested or multiplex RT-PCR, testing only the most common P and G-types. We observed G1 and P[8] to be the most prevalent strains in Africa, with values around 31% and 43%, respectively. Yet if all the genotypes with the following highest prevalence were added ((G1 + G2, G3, G9) and (P[8] + P[6], P[4])), these figures would represent 80% and 99% of the total prevalence. The combination G1P[8] was the most reported in the studies (around 22%). This review study demonstrated an increased strain diversity in the past two decades, which could represent a challenge to the efficacy of the current vaccine.

In this work, alpha-tocopherol (α-TOC) was encapsulated in poly(lactic acid) nanoparticles (PLA NPs) and added to low-density polyethylene (LDPE) films with the aim of producing an active film for food packaging applications. PLA NPs loaded with α-TOC were produced through nanoprecipitation and dried using two methods (freeze-dryer and oven). LDPE-based films with final polymeric matrix concentrations of 10 and 20 g/kg were then produced through blow extrusion. The results showed that LDPE-based films loaded with α-TOC can be produced using blow extrusion, and a good distribution of PLA NPs can be obtained within the LDPE matrix as observed using scanning electron microscopy (SEM). The mechanical properties were affected by the incorporation of α-TOC and PLA NPs loaded with α-TOC, with the observation of a decrease in tensile strength and Young's Modulus values and an increase in elongation at break. Regarding water vapor permeability, the films showed a reduction in the values with the addition of α-TOC and PLA NPs loaded with α-TOC compared to the LDPE film (control). Films with α-TOC in the free state and loaded in PLA NPs showed antioxidant activity, but their behavior was affected by the encapsulation process.

Background: Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women., Objective: To assess the use of MS disease-modifying therapies (DMTs) during pregnancy in France over the last decade, marked by an increasing DMTs availability., Methods: All pregnancies ended from April 2010 to December 2021 in women with MS were identified based on the nationwide Mother-Child Register EPI-MERES, built from the French National Health Data System ( Système National des Données de Santé (SNDS))., Results: Of a total of 20,567 pregnancies in women with MS, 7587 were exposed to DMT. The number of DMT-exposed pregnancies markedly increased from 1079 in 2010-2012 to 2413 in 2019-2021 (+124%), especially those exposed to glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20. Among pregnancies of women on DMT 6 months before pregnancy, 78.0% underwent DMT discontinuation and 7.6% switched DMT, generally before (33.0% and 77.0%, respectively) or during the first trimester of pregnancy (58.3% and 17.8%, respectively). DMT discontinuation decreased from 84.0% in 2010-2012 to 72.4% in 2019-2021 and was less frequent among women aged ⩾35 years and those socioeconomically disadvantaged., Conclusion: Despite MS therapeutic management adaptations to pregnancy, exposure during pregnancy to treatments whose safety profile has not yet been clearly established has increased sharply over the last decade., Competing Interests: Data AvailabilityAccording to data protection and the French regulation, the authors cannot publicly release the data from the French National Health Data System (SNDS). However, any person or structure, public or private, for-profit or non-profit, is able to access SNDS data upon authorization from the French Data Protection Office (CNIL Commission Nationale de l’Informatique et des Libertés) to carry out a study, a research, or an evaluation of public interest (https://www.snds.gouv.fr/SNDS/Processus-d-acces-aux-donnees and https://www.indsante.fr/). Here is a non-author point of contact where data requests can be sent https://www.health-data-hub.fr/contact. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This work reports the first electrochemical bioplatform developed for the determination of human endostatin (HE), a biomarker with recognized antiangiogenic potential whose elevated circulating levels have also been associated with the development of aggressive cancers. The developed electroanalytical biotool combines the benefits of using magnetic microparticles for the implementation of sandwich immunoassays and amperometric transduction on disposable carbon electrodes. A limit of detection (LOD) of 34.1 pg mL -1 for HE standards and a selectivity suitable for its foray into the clinical oncology area, are demonstrated. The determination of HE in clinical samples such as lysates and secretomes of colorectal cancer (CRC) cells, plasma, and tissue samples from patients with CRC in different stages, has been faced with satisfactory results showing the ability for discriminating the metastatic capabilities of cells and for identifying and staging CRC patients. The developed bioplatform allows precise quantitative determinations, requiring minimal pre-treatments and sample amounts in only 75 min. In addition, due to the instrumentation and the type of substrates used in the detection step, the biotool is compatible with implementation in multiplexed and/or point-of-need devices, features in which this bioplatform is advantageous with respect to the enzyme linked immunosorbent assay (ELISA) or immunoblotting technologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Limited data are available on the consequences of prenatal exposure to vedolizumab and ustekinumab. We aimed to compare the safety of vedolizumab and ustekinumab with that of anti-tumor necrosis factor (TNF) in pregnant women with inflammatory bowel diseases (IBD)., Methods: Using nationwide, comprehensive data of the EPI-MERES registry, we identified pregnancies in women with IBD in France, exposed to anti-TNF, vedolizumab, and ustekinumab between 2014 and 2021. We compared pregnancy outcomes and complications in the offspring according to treatment exposure during pregnancy. We applied a propensity score matching for maternal, IBD, and pregnancy characteristics., Results: Three hundred ninety-eight pregnancies exposed to vedolizumab were compared with 1592 pregnancies exposed to anti-TNF; 464 pregnancies exposed to ustekinumab were compared with 1856 pregnancies exposed to anti-TNF. Overall, compared with anti-TNF, neither vedolizumab nor ustekinumab was associated with increased risks of abortion, caesarean section, stillbirth, preterm birth, serious infections, malignancies, or congenital abnormality in children. Women exposed to ustekinumab had an increased risk of small for gestational age births., Conclusions: Overall, the safety of vedolizumab and ustekinumab compared with anti-TNF use during pregnancy is reassuring. Further studies are needed to confirm these findings., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In this paper, a computational approach based on numerical dissipation is proposed to simulate rocking blocks. A rocking block is idealized as a solid body interacting with its foundation through a contact-based formulation. An implicit time integration scheme with numerical dissipation, set to optimally treat dissipation in contact problems, is employed. The numerical dissipation is ruled by the time step and the rocking dissipative phenomenon at impacts is accurately predicted without any damping model. A broad numerical campaign is conducted to define a regression law in analytic form for the setting of the time step, depending on the block size and aspect ratio, the contact stiffness, as well as the coefficient of restitution selected. The so-obtained regression law appears accurate and an a posteriori validation with cases not in the training dataset confirms the effectiveness of the approach. Finally, the comparison with available experimental tests highlights the approach efficacy for free rocking and harmonic loading cases (in a deterministic sense), and for earthquake-like loading cases (in a statistical sense). It is found that rocking blocks with sizes of interest for structural engineering (e.g., cultural heritage structures) can be simulated with time steps within 10 -3  ÷ 10 -1  s, so allowing very fast computations., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2024.)

Introduction:  Obesity is a risk factor for venous thromboembolism, but studies evaluating its association with pulmonary embolism (PE) in patients with suspected PE are lacking., Objectives:  To evaluate whether body mass index (BMI) and obesity (i.e., BMI ≥30 kg/m 2 ) are associated with confirmed PE in patients with suspected PE and to assess the efficiency and safety of the age-adjusted D-dimer strategy in obese patients., Methods:  We conducted a secondary analysis of a multinational, prospective study, in which patients with suspected PE were managed according to the age-adjusted D-dimer strategy and followed for 3 months. Outcomes were objectively confirmed PE at initial presentation, and efficiency and failure rate of the diagnostic strategy. Associations between BMI and obesity, and PE were examined using a log-binomial model that was adjusted for clinical probability and hypoxia., Results:  We included 1,593 patients (median age: 59 years; 56% women; 22% obese). BMI and obesity were not associated with confirmed PE. The use of the age-adjusted instead of the conventional D-dimer cut-off increased the proportion of obese patients in whom PE was considered ruled out without imaging from 28 to 38%. The 3-month failure rate in obese patients who were left untreated based on a negative age-adjusted D-dimer cut-off test was 0.0% (95% confidence interval: 0.0-2.9%)., Conclusion:  BMI on a continuous linear scale and obesity were not predictors of confirmed PE among patients presenting with a clinical suspicion of PE. The age-adjusted D-dimer strategy appeared safe in ruling out PE in obese patients with suspected PE., Competing Interests: None declared., (Thieme. All rights reserved.)