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Objective: To evaluate the effectiveness of ChatGPT in providing insights into common urinary incontinence concerns within urogynecology. By analyzing the model's responses against established benchmarks of accuracy, completeness, and safety, the study aimed to quantify its usefulness for informing patients and aiding healthcare providers., Methods: An expert-driven questionnaire was developed, inviting urogynecologists worldwide to assess ChatGPT's answers to 10 carefully selected questions on urinary incontinence (UI). These assessments focused on the accuracy of the responses, their comprehensiveness, and whether they raised any safety issues. Subsequent statistical analyses determined the average consensus among experts and identified the proportion of responses receiving favorable evaluations (a score of 4 or higher)., Results: Of 50 urogynecologists that were approached worldwide, 37 responded, offering insights into ChatGPT's responses on UI. The overall feedback averaged a score of 4.0, indicating a positive acceptance. Accuracy scores averaged 3.9 with 71% rated favorably, whereas comprehensiveness scored slightly higher at 4 with 74% favorable ratings. Safety assessments also averaged 4 with 74% favorable responses., Conclusion: This investigation underlines ChatGPT's favorable performance across the evaluated domains of accuracy, comprehensiveness, and safety within the context of UI queries. However, despite this broadly positive reception, the study also signals a clear avenue for improvement, particularly in the precision of the provided information. Refining ChatGPT's accuracy and ensuring the delivery of more pinpointed responses are essential steps forward, aiming to bolster its utility as a comprehensive educational resource for patients and a supportive tool for healthcare practitioners., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

False political information-misinformation or disinformation-is widely spread on social media. Individual social media users play a large part in this. However, only a minority actively share false material. It is important to establish what sets these individuals apart from those who do not, and why they do it. Motivations for sharing may vary and are likely to differ between people who share false material unknowingly and on purpose. In this paper we consider the extent to which individual differences in personality and other variables, and motivations for sharing, are associated with the likelihood of people sharing false political information both accidentally and deliberately. In a series of four studies (Ns = 614, 563, 627, 113) we examined predictors of sharing false political information using different methodological approaches. Across the four studies, a key finding was that positive schizotypy is associated with measures of sharing false information both accidentally and deliberately. Motivations for sharing political information online were also relevant, with sharing for reasons of 'raising awareness' appearing particularly important. Implications for research and practice are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Buchanan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The incidence of beta-lactam resistance among clinical isolates is a major health concern. A key method to study the emergence of antibiotic resistance is adaptive laboratory evolution. However, in the case of the beta-lactam ampicillin, bacteria evolved in laboratory settings do not recapitulate clinical-like resistance levels, hindering efforts to identify major evolutionary paths and their dependency on genetic background. Here, we used the Microbial Evolution and Growth Arena (MEGA) plate to select ampicillin-resistant Escherichia coli mutants with varying degrees of resistance. Whole-genome sequencing of resistant isolates revealed that ampicillin resistance was acquired via a combination of single-point mutations and amplification of the gene encoding beta-lactamase AmpC. However, blocking AmpC-mediated resistance revealed latent adaptive pathways: strains deleted for ampC were able to adapt through combinations of changes in genes involved in multidrug resistance encoding efflux pumps, transcriptional regulators, and porins. Our results reveal that combinations of distinct genetic mutations, accessible at large population sizes, can drive high-level resistance to ampicillin even independently of beta-lactamases., (© 2024. The Author(s).)

In recent decades, a growing number of discoveries in mathematics have been assisted by computer algorithms, primarily for exploring large parameter spaces. As computers become more powerful, an intriguing possibility arises-the interplay between human intuition and computer algorithms can lead to discoveries of mathematical structures that would otherwise remain elusive. Here, we demonstrate computer-assisted discovery of a previously unknown mathematical structure, the conservative matrix field. In the spirit of the Ramanujan Machine project, we developed a massively parallel computer algorithm that found a large number of formulas, in the form of continued fractions, for numerous mathematical constants. The patterns arising from those formulas enabled the construction of the first conservative matrix fields and revealed their overarching properties. Conservative matrix fields unveil unexpected relations between different mathematical constants, such as π and ln(2), or e and the Gompertz constant. The importance of these matrix fields is further realized by their ability to connect formulas that do not have any apparent relation, thus unifying hundreds of existing formulas and generating infinitely many new formulas. We exemplify these implications on values of the Riemann zeta function ζ (n), studied for centuries across mathematics and physics. Matrix fields also enable new mathematical proofs of irrationality. For example, we use them to generalize the celebrated proof by Apéry of the irrationality of ζ (3). Utilizing thousands of personal computers worldwide, our research strategy demonstrates the power of large-scale computational approaches to tackle longstanding open problems and discover unexpected connections across diverse fields of science., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.

The relation between the processing of space and time in the brain has been an enduring cross-disciplinary question. Grid cells have been recognized as a hallmark of the mammalian navigation system, with recent studies attesting to their involvement in the organization of conceptual knowledge in humans. To determine whether grid-cell-like representations support temporal processing, we asked subjects to mentally simulate changes in age and time-of-day, each constituting "trajectory" in an age-day space, while undergoing fMRI. We found that grid-cell-like representations supported trajecting across this age-day space. Furthermore, brain regions concurrently coding past-to-future orientation positively modulated the magnitude of grid-cell-like representation in the left entorhinal cortex. Finally, our findings suggest that temporal processing may be supported by spatially modulated systems, and that innate regularities of abstract domains may interface and alter grid-cell-like representations, similarly to spatial geometry., (Copyright © 2024. Published by Elsevier Ltd.)

Breast cancer chemotherapy/immunotherapy can be associated with treatment-limiting cardiotoxicity. Radiomics techniques applied to ultrasound, known as ultrasomics, can be used in cardio-oncology to leverage echocardiography for added prognostic value. To utilize ultrasomics features collected prior to antineoplastic therapy to enhance prediction of mortality and heart failure (HF) in patients with breast cancer. Patients were retrospectively recruited in a study at the West Virginia University Cancer Institute. The final inclusion criteria were met by a total of 134 patients identified for the study. Patients were imaged using echocardiography in the parasternal long axis prior to receiving chemotherapy. All-cause mortality and HF, developed during treatment, were the primary outcomes. 269 features were assessed, grouped into four major classes: demographics (n = 21), heart function (n = 7), antineoplastic medication (n = 17), and ultrasomics (n = 224). Data was split into an internal training (60%, n = 81) and testing (40%, n = 53) set. Ultrasomics features augmented classification of mortality (area under the curve (AUC) 0.89 vs. 0.65, P = 0.003), when compared to demographic variables. When developing a risk prediction score for each feature category, ultrasomics features were significantly associated with both mortality (P = 0.031, log-rank test) and HF (P = 0.002, log-rank test). Further, only ultrasomics features provided significant improvement over demographic variables when predicting mortality (C-Index: 0.78 vs. 0.65, P = 0.044) and HF (C-Index: 0.77 vs. 0.60, P = 0.017), respectively. With further investigation, a clinical decision support tool could be developed utilizing routinely obtained patient data alongside ultrasomics variables to augment treatment regimens., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Approximately 30% of patients with a history of repaired cleft palate (CP) go on to suffer from velopharyngeal dysfunction (VPD). This study discusses the operative management of VPD and postoperative speech outcomes in a cohort of CP patients., Setting: An academic tertiary pediatric care center., Methods: Retrospective cohort study., Patients: Patients with history of repaired CP (Veau I-IV) who underwent operative management of VPD between January 1st, 2010 and December 31st, 2020. Operative modalities were posterior pharyngeal flap (PPF), sphincter pharyngoplasty (SPP), Furlow palate re-repair, and buccal myomucosal flap palate lengthening (PL)., Outcome Measures: The primary outcome measure is postoperative speech improvement evaluated by the Pittsburgh Weighted Speech Scale (PWSS)., Results: 97 patients met inclusion criteria. 38 patients with previous straight-line primary palatoplasty underwent Furlow re-repair; these patients were significantly younger (7.62 vs 11.14, P  < .001) and were more likely to have severe VPD per PWSS (OR 4.28, P  < .01, 95% CI 1.46-12.56) when compared to VPD patients with previous Furlow repair. 21.1% of these patients required an additional non-revisional VPD procedure. The remaining patients underwent a non-revision procedure (26 PPF, 22 SPP, 11 PL); all experienced significant ( P  < .001 on paired t-test) reductions in PWSS total and subgroup VPD severity scores without difference in improvement between operation types. SPP was statistically associated with all-cause complication (OR 2.79, 95% CI 1.03-7.59, P  < .05) and hyponasality (OR 3.27, 95% CI 1.112-9.630, P  < .05)., Conclusion: Furlow re-repair reduced need for additional VPD operations. Speech outcomes between non-revisional operations are comparable, but increased complications were seen in SPP., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Clinical assessments often fail to discriminate between unipolar and bipolar depression and identify individuals who will develop future (hypo)manic episodes. To address this challenge, we developed a brain-based graph-theoretical predictive model (GPM) to prospectively map symptoms of anhedonia, impulsivity, and (hypo)mania. Individuals seeking treatment for mood disorders (n = 80) underwent an fMRI scan, including (i) resting-state and (ii) a reinforcement-learning (RL) task. Symptoms were assessed at baseline as well as at 3- and 6-month follow-ups. A whole-brain functional connectome was computed for each fMRI task, and the GPM was applied for symptom prediction using cross-validation. Prediction performance was evaluated by comparing the GPM to a corresponding null model. In addition, the GPM was compared to the connectome-based predictive modeling (CPM). Cross-sectionally, the GPM predicted anhedonia from the global efficiency (a graph theory metric that quantifies information transfer across the connectome) during the RL task, and impulsivity from the centrality (a metric that captures the importance of a region) of the left anterior cingulate cortex during resting-state. At 6-month follow-up, the GPM predicted (hypo)manic symptoms from the local efficiency of the left nucleus accumbens during the RL task and anhedonia from the centrality of the left caudate during resting-state. Notably, the GPM outperformed the CPM, and GPM derived from individuals with unipolar disorders predicted anhedonia and impulsivity symptoms for individuals with bipolar disorders. Importantly, the generalizability of cross-sectional models was demonstrated in an external validation sample. Taken together, across DSM mood diagnoses, efficiency and centrality of the reward circuit predicted symptoms of anhedonia, impulsivity, and (hypo)mania, cross-sectionally and prospectively. The GPM is an innovative modeling approach that may ultimately inform clinical prediction at the individual level., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Purpose: Pelvic organ prolapse (POP) and overactive bladder (OAB) commonly affect the aging female population. We aimed to investigate the possible relationship between the two, as reflected by urodynamic studies., Methods: A retrospective analysis was conducted on women who underwent urodynamic studies at a university-affiliated tertiary medical center from January 2018 to January 2021. Women presenting with urge incontinence and diagnosed with detrusor overactivity (DO) were included in the study. Based on the presence or absence of a modified POP-Q ≥ grade 2, these women were categorized into two groups. Data on general demographics, clinical symptoms, and urodynamic findings were extracted and compared using SPSS., Results: During the study period, 949 urodynamic evaluations were performed. Of these, 303 (31.92%) reported urge incontinence. Out of this subset, 151 (49.83%) were diagnosed with DO. Within this group, 18 (11.9%) had POP, while 134 (88.1%) did not. The POP group had a notably higher incidence of prior vaginal hysterectomy and anterior colporrhaphy (p = 0.02 and p = 0.01, respectively). While most urodynamic parameters were similar between groups, there was a significant increase in hesitancy in the POP group (13 s vs 8 s, p = 0.03). There was a trend indicating a reduced median Q max (12 ml/s vs. 18 ml/s, p = 0.06) and an increased flow time (55 s vs 40 s, p = 0.08) in the POP group., Conclusion: The urodynamic profile of the POP group suggests an obstructive voiding pattern. Further longitudinal research is essential to fully understand the relationship between POP and OAB., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Competency-based medical education (CBME) has gained prominence as an innovative model for post-graduate medical education, yet its implementation poses significant challenges, especially with regard to its sustainability. Drawing on paradox theory, we suggest that revealing the paradoxes underlying these challenges may contribute to our understanding of post graduate competency-based medical education (PGCBME) implementation processes and serve as a first-step in enhancing better implementation. Thus, the purpose of the current study is to identify the paradoxes associated with PGCBME implementation., Method: A qualitative study was conducted, as part of a larger action research, using in-depth semi-structured interviews with fellows and educators in eight Neonatal wards., Results: Analysis revealed that the PGCBME program examined in this study involves three different levels of standardization, each serving as one side of paradoxical tensions; (1) a paradox between the need for standardized assessment tools and for free-flow flexible assessment tools, (2) a paradox between the need for a standardized implementation process across all wards and the need for unique implementation protocols in each ward; and 3) a paradox between the need for a standardized meaning of competency proficiency and the need for flexible and personal competency achievement indicators., Conclusions: Implementing PGCBME programs involves many challenges, some of which are paradoxical, i.e. two contradictory challenges in which solving one challenge exacerbates another. Revealing these paradoxes is important in navigating them successfully.

In vitro experiments and cryo-EM structures of p97 and its cofactor, Ufd1/Npl4 (UN), elucidated substrate processing. Yet, the structural transitions and the related ATPase cycle upon UN binding remain unresolved. We captured two discrete conformations: One in which D1 protomers are ATP bound, while the D2 subunits are in the ADP state, presumably required for substrate engagement with the D2 pore; and a heterologous nucleotide state within the D1 ring in which only two NTDs are in the "up" ATP state that favors UN binding. Further analysis suggests that initially, UN binds p97's non-symmetrical conformation, this association promotes a structural transition upon which five NTDs shift to an "up" state and are poised to bind ATP. The UBXL domain of Npl4 was captured bound to an NTD in the ADP state, demonstrating a conformation that may provide directionality to incoming substrate and introduce the flexibility needed for substrate processing., Competing Interests: The authors declare no competing interests., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Sex-specific predilection in neurological diseases caused by mutations in autosomal genes is a phenomenon whose molecular basis is poorly understood. We studied females of consanguineous Bedouin kindred presenting with severe global developmental delay and epilepsy., Methods: Linkage analysis, whole exome sequencing, generation of CRISPR/cas9 knock-in mice, mouse behaviour and molecular studies RESULTS: Linkage analysis and whole exome sequencing studies of the affected kindred delineated a ~5 Mbp disease-associated chromosome 2q35 locus, containing a novel homozygous frameshift truncating mutation in ZNF142 , in line with recent studies depicting similar ZNF142 putative loss-of-function human phenotypes with female preponderance. We generated knock-in mice with a truncating mutation adjacent to the human mutation in the mouse ortholog. Behaviour studies of homozygous Zfp142 R1508* mice showed significant phenotype only in mutant females, with learning and memory deficits, hyperactivity and aberrant loss of fear of open spaces. Bone marrow and spleen of homozygous Zfp142 R1508* mice showed depletion of lymphoid and haematopoietic cells, mostly in females. RT-PCR showed lower expression of Zpf142 in brain compartments of female versus male wild-type mice. RNA-seq studies of hippocampus, hypothalamus, cortex and cerebellum of female wild-type versus homozygous Zfp142 R1508* mice demonstrated differentially expressed genes. Notably, expression of Taok1 in the cortex and of Mllt6 in the hippocampus was downregulated in homozygous Zfp142 R1508* mice. Taok1 mutations have been associated with aberrant neurodevelopment and behaviour. Mllt6 expression is regulated by sex hormones and Mllt6 null-mutant mice present with haematopoietic, immune system and female-specific behaviour phenotypes., Conclusion: ZNF142 mutation downregulates Mllt6 and Taok1, causing a neurodevelopmental phenotype in humans and mice with female preponderance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper presents the data (images, observations, metadata) of three different deployments of camera traps in the Amsterdam Water Supply Dunes, a Natura 2000 nature reserve in the coastal dunes of the Netherlands. The pilots were aimed at determining how different types of camera deployment (e.g. regular vs. wide lens, various heights, inside/outside exclosures) might influence species detections, and how to deploy autonomous wildlife monitoring networks. Two pilots were conducted in herbivore exclosures and mainly detected European rabbits ( Oryctolagus cuniculus ) and red fox ( Vulpes vulpes ). The third pilot was conducted outside exclosures, with the European fallow deer ( Dama dama ) being most prevalent. Across all three pilots, a total of 47,597 images were annotated using the Agouti platform. All annotations were verified and quality-checked by a human expert. A total of 2,779 observations of 20 different species (including humans) were observed using 11 wildlife cameras during 2021-2023. The raw image files (excluding humans), image metadata, deployment metadata and observations from each pilot are shared using the Camtrap DP open standard and the extended data publishing capabilities of GBIF to increase the findability, accessibility, interoperability, and reusability of this data. The data are freely available and can be used for developing artificial intelligence (AI) algorithms that automatically detect and identify species from wildlife camera images., (© 2024 The Authors.)

Efforts to tap into the broad antimicrobial, insecticidal, and antioxidant activities of essential oils (EOs) are limited due to their strong odor and susceptibility to light and oxidation. Encapsulation of EOs and subsequent drying overcome these limitations and extend their applications. This study characterized freeze-dried (lyophilized) emulsions of eugenol (EU) and thymol (TY) EOs, encapsulated by chemically unmodified cellulose, a sustainable and low-cost resource. High-resolution scanning electron microscopy showed successful lyophilization. While the observed "flake-like" structure of the powders differed significantly from that of the emulsified microcapsules, useful properties were retained. Fourier transform infrared spectroscopy confirmed the presence of EOs in their corresponding powders and thermo-gravimetric analysis demonstrated high encapsulation efficiency (87-88%), improved thermal stability and resistance to evaporation, and slow EO release rates in comparison to their free forms. The lightweight and low-cost cellulose encapsulation, together with the results showing retained properties of the dried powder, enable the use of EOs in applications requiring high temperatures, such as EO incorporation into polymer films, that can be used to protect agricultural crops from microbial infections.

The objective of this narrative review was to assess current literature regarding acquisition and consolidation of physician practices in the United States (US). The acquisition and consolidation of physician practices is a trend affecting patient care, quality of services, healthcare economics and the daily practice of physicians. As practices are acquired by fellow physician groups, private equity investors and entities such as hospitals or large healthcare systems, it is important to better understand the underlying forces driving these transactions and their effects. This is a narrative review of peer-reviewed publications to determine what current literature has covered regarding the acquisition and consolidation of physician practices in the US regarding risks and benefits of this trend. Sources included the SCOPUS, Medline- PUBMED and Web of Science databases. Peer reviewed publications from 2009 to 2022 were included for initial review and curation for relevance using the search terms "physician" and "practice" with either "acquisition" or "consolidation". Synthesis conducted after narrowing down of relevant articles did not use quantitative measurements, but instead examined overall trends, as well as risk and benefits of ongoing acquisition and consolidation in a narrative format. Journal articles focused on physician consolidation in the US often reported increases in physician numbers with decreases in numbers of individual practices. Private equity quantitative analyses reported rapidly accelerating acquisitions driven by these investors, and vertical integration scholarly work reported frequent geographic consolidation of nearby practitioners. Risks associated with these transactions included such items as decreased physician autonomy and higher cost of care. Benefits included practice stability, improved negotiation with insurers and improved access to resources., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Tewfik et al.)

Objectives: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies., Methods: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies., Results: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups., Conclusion: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: A multi-biomarker disease activity (MBDA)-based cardiovascular disease (CVD) risk score was developed and internally validated in a Medicare cohort to predict 3-year risk for myocardial infarction (MI), stroke or CVD death in patients with rheumatoid arthritis (RA). It combines the MBDA score, leptin, MMP-3, TNF-R1, age and four clinical variables. We are now externally validating it in a younger RA cohort., Methods: Claims data from a private aggregator were linked to MBDA test data to create a cohort of RA patients ≥18 years old. A univariable Cox proportional hazards regression model was fit using the MBDA-based CVD risk score as sole predictor of time-to-a-CVD event (hospitalized MI or stroke). Hazard ratio (HR) estimate was determined for all patients and for clinically relevant subgroups. A multivariable Cox model evaluated whether the MBDA-based CVD risk score adds predictive information to clinical data., Results: 49,028 RA patients (340 CVD events) were studied. Mean age was 52.3 years; 18.3% were male. HR for predicting 3-year risk of a CVD event by the MBDA-based CVD risk score in the full cohort was 3.99 (95% CI: 3.51-4.49, p = 5.0×10-95). HR were also significant for subgroups based on age, comorbidities, disease activity, and drug use. In a multivariable model, the MBDA-based CVD risk score added significant information to hypertension, diabetes, tobacco use, history of CVD, age, sex and CRP (HR = 2.27, p = 1.7×10-7)., Conclusion: The MBDA-based CVD risk score has been externally validated in an RA cohort that is younger than and independent of the Medicare cohort that was used for development and internal validation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ES, BM, DDFII, EH, CLC, RB-S, AG, and JSL are or were employed by Myriad Genetics during the conduct of the study and received salaries and may have received stock grants/options as compensation. EH has been employed by Labcorp. JC received grants or contracts from Abbvie, Amgen, BMS, Corevitas, Janssen, Lilly, Novartis, Myriad, Pfizer, Sanofi, Setpoint, Scipher, and UCB and received consulting fees from Abbvie, Amgen, BMS, Corevitas, Janssen, Lilly, Novartis, Myriad, Pfizer, Sanofi, Setpoint, Scipher, and UCB. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Sasso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions., (© 2024. The Author(s).)

Background: Sports and physical activity are known risk factors for pelvic floor dysfunction (PFD). The aim of this study is to examine the impact of amateur running on PFD, quality of life (QoL), and sexual function., Methods: Amateur runners were contacted through social media. Their PFD, sexual function, and QoL were evaluated by self-reporting validated questionnaires (PFDI-20, PISQ-12, IIQ-7). They were divided by degree of effort into two categories, 'High effort' and 'Moderate effort'. The differences between the two groups were examined by a Mann-Whitney U Test, T-Test, and Chi-square test., Results: 180 women were included. A high incidence of PFD was found among 'High effort' runners in comparison to 'Moderate effort' runners. In addition, women who scored above the median in the PFDI-20 showed significantly greater impairment in QoL and sexual function. Interestingly, the 'High effort' group reported experiencing higher intensity orgasms compared with women in the 'Moderate effort' group. A correlation was also found between the weekly running distance and the intensity of orgasm experienced (P value = 0.004)., Conclusion: 'High effort' runners present a higher incidence of PFD in comparison to 'Moderate effort' runners. Professional pelvic floor muscle training counselling should be considered even for amateur runners. Future interventional physical therapy studies should be carried out in order to investigate preventative strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To recognize prognostic factors for better final visual acuity (VA) in patients presenting with submacular hemorrhage (SMH) secondary to exudative age-related macular degeneration ., Methods: This retrospective study included patients who presented to a tertiary ophthalmology department between 2012 and 2019 with SMH and were treated by pars plana vitrectomy (PPV) or injection of tissue plasminogen activator (tPA) with pneumatic displacement. Baseline characteristics included demographic data, VA and optical coherence tomography (OCT) characteristics of the SMH. Patients were divided into groups by improvement of at least 2 lines in BCVA (best corrected visual acuity), and by having a final BCVA better than 20/200., Results: Forty-three eyes of 43 patients were included. Mean age was 86.72 ± 7.18. Prognostic factors for final VA better than 20/200 included better VA at presentation (1.25 vs 1.90 logMAR, p  < 0.001), smaller area of SMH in the infra-red image (19.47 mm 2 vs 38.45 mm 2 , p  = 0.024), and lower height of SMH as measured by OCT (713.5 µm vs 962.5 µm, p  = 0.03). Third of the patients improved in ≥2 lines from presentation, all in the group of the pneumatic and TPA displacement., Conclusion: Smaller SMHs with good VA at presentation have a better chance for improvement and result in a better final VA. These patients may benefit the most from pneumatic displacement of the SMH with intravitreal tPA and gas., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Fetal acidosis among low-risk pregnancies is not common; however, identifying those at risk for this complication antenatally is of great interest. We aimed to assess the correlation between the total decelerations area during the last 120 min of fetal monitoring prior to delivery and neonatal acidemia in low-risk pregnancies and whether the total acceleration area has a protective effect in the presence of decelerations. A retrospective cohort study was conducted among women with term low-risk pregnancies. A researcher blinded to fetal outcomes interpreted electronic fetal monitor patterns during the 120 min prior to delivery. The primary outcome was fetal acidemia, defined as umbilical artery pH below 7.10. The correlation between the total decelerations and accelerations areas and cord blood pH was tested using the Spearman correlation coefficient. A total of 109 women were included and of these, six (5.5%) delivered infants with cord blood pH < 7.10. A significant correlation was demonstrated between the total decelerations area and cord blood pH (p = 0.01). No correlation was found between the total accelerations area and cord blood pH. Among low-risk pregnancies, a correlation was found between the total decelerations area but not the total accelerations area during the final 120 min of labor and cord blood pH., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: To examine whether a correlation exists between electronic fetal monitoring (EFM) in the final 120 minute prior to delivery and neonatal cord blood pH among parturients with preeclampsia., Study Design: A retrospective cohort study of parturients with term and near-term preeclampsia who delivered at Soroka University Medical Center between 2013 and 2020 was conducted. EFM tracings, demographical data, and obstetrical outcomes were retrieved from the patients' electronic medical records. Using MATLAB program, area under the curve (AUC) measurements were applied. Correlation was calculated using the Spearman's correlation coefficient., Results: EFM of 88 parturients with preeclampsia were assessed. A significant negative correlation was demonstrated between cord blood pH and the decelerations AUC, total decelerations duration, and deceleration depth. No correlation was demonstrated between area over the curve (acceleration) and cord blood pH. In a multivariate linear regression, total deceleration AUC was found independently negatively associated with cord blood pH (beta = -0.264, p  = 0.011) controlling for second stage of labor duration and induction of labor., Conclusion: Among parturients with preeclampsia, EFM indices may assist in the diagnosis of fetal acidemia. Further studies are needed to strengthen and establish the use of electronic EFM in the management of labor and delivery., Key Points: · A negative correlation was demonstrated between cord blood pH and the decelerations AUC.. · Total deceleration AUC was found independently negatively associated.. · Among parturients with preeclampsia, EFM indices may assist in the diagnosis of fetal acidemia.., Competing Interests: None declared., (Thieme. All rights reserved.)

Each sense serves a different specific function in spatial perception, and they all form a joint multisensory spatial representation. For instance, hearing enables localization in the entire 3D external space, while touch traditionally only allows localization of objects on the body (i.e., within the peripersonal space alone). We use an in-house touch-motion algorithm (TMA) to evaluate individuals' capability to understand externalized 3D information through touch, a skill that was not acquired during an individual's development or in evolution. Four experiments demonstrate quick learning and high accuracy in localization of motion using vibrotactile inputs on fingertips and successful audio-tactile integration in background noise. Subjective responses in some participants imply spatial experiences through visualization and perception of tactile "moving" sources beyond reach. We discuss our findings with respect to developing new skills in an adult brain, including combining a newly acquired "sense" with an existing one and computation-based brain organization., Competing Interests: As mentioned also in the STAR Methods section, we declare a patent has been filed based on the technology featured in the current manuscript. The author A.A. is a co-founder and a member of the scientific advisory board of Remepy and Davinci Neuroscience Inc., (© 2024 The Authors.)

Electrochemical CO 2 reduction reaction in aqueous electrolytes is a promising route to produce added-value chemicals and decrease carbon emissions. However, even in Gas-Diffusion Electrode devices, low aqueous CO 2 solubility limits catalysis rate and selectivity. Here, we demonstrate that when assembled over a heterogeneous electrocatalyst, a film of nitrile-modified Metal-Organic Framework (MOF) acts as a remarkable CO 2 -solvation layer that increases its local concentration by ~27-fold compared to bulk electrolyte, reaching 0.82 M. When mounted on a Bi catalyst in a Gas Diffusion Electrode, the MOF drastically improves CO 2 -to-HCOOH conversion, reaching above 90% selectivity and partial HCOOH currents of 166 mA/cm 2 (at -0.9 V vs RHE). The MOF also facilitates catalysis through stabilization of reaction intermediates, as identified by operando infrared spectroscopy and Density Functional Theory. Hence, the presented strategy provides new molecular means to enhance heterogeneous electrochemical CO 2 reduction reaction, leading it closer to the requirements for practical implementation., (© 2024. The Author(s).)

Most human emotion recognition methods largely depend on classifying stereotypical facial expressions that represent emotions. However, such facial expressions do not necessarily correspond to actual emotional states and may correspond to communicative intentions. In other cases, emotions are hidden, cannot be expressed, or may have lower arousal manifested by less pronounced facial expressions, as may occur during passive video viewing. This study improves an emotion classification approach developed in a previous study, which classifies emotions remotely without relying on stereotypical facial expressions or contact-based methods, using short facial video data. In this approach, we desire to remotely sense transdermal cardiovascular spatiotemporal facial patterns associated with different emotional states and analyze this data via machine learning. In this paper, we propose several improvements, which include a better remote heart rate estimation via a preliminary skin segmentation, improvement of the heartbeat peaks and troughs detection process, and obtaining a better emotion classification accuracy by employing an appropriate deep learning classifier using an RGB camera input only with data. We used the dataset obtained in the previous study, which contains facial videos of 110 participants who passively viewed 150 short videos that elicited the following five emotion types: amusement, disgust, fear, sexual arousal, and no emotion, while three cameras with different wavelength sensitivities (visible spectrum, near-infrared, and longwave infrared) recorded them simultaneously. From the short facial videos, we extracted unique high-resolution spatiotemporal, physiologically affected features and examined them as input features with different deep-learning approaches. An EfficientNet-B0 model type was able to classify participants' emotional states with an overall average accuracy of 47.36% using a single input spatiotemporal feature map obtained from a regular RGB camera.

Sterile alpha and TIR motif-containing 1 (SARM1) is a protein involved in programmed death of injured axons. Following axon injury or a drug-induced insult, the TIR domain of SARM1 degrades the essential molecule nicotinamide adenine dinucleotide (NAD+), leading to a form of axonal death called Wallerian degeneration. Degradation of NAD+ by SARM1 is essential for the Wallerian degeneration process, but accumulating evidence suggest that other activities of SARM1, beyond the mere degradation of NAD+, may be necessary for programmed axonal death. In this study we show that the TIR domains of both human and fruit fly SARM1 produce 1''-2' and 1''-3' glycocyclic ADP-ribose (gcADPR) molecules as minor products. As previously reported, we observed that SARM1 TIR domains mostly convert NAD+ to ADPR (for human SARM1) or cADPR (in the case of SARM1 from Drosophila melanogaster). However, we now show that human and Drosophila SARM1 additionally convert ~0.1-0.5% of NAD+ into gcADPR molecules. We find that SARM1 TIR domains produce gcADPR molecules both when purified in vitro and when expressed in bacterial cells. Given that gcADPR is a second messenger involved in programmed cell death in bacteria and likely in plants, we propose that gcADPR may play a role in SARM1-induced programmed axonal death in animals., Competing Interests: P.J.K, R.S, G.A and A.L. are inventors of a patent application related to the production and utility of gcADPR. R.S. is a scientific cofounder and advisor of BiomX and Ecophage. The rest of the authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Garb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose The purpose of this study is to comprehensively evaluate the role of different echocardiography parameters in breast cancer patients undergoing chemotherapy. While echocardiography examination with calculation of ejection fraction (EF), is pivotal for patient monitoring, its operator dependence and insensitivity to subtle changes in left ventricular (LV) contractility present challenges. Global longitudinal strain (GLS), derived from speckle tracking, is more sensitive and stable than EF. Our research aimed to delineate supplementary echocardiography measurements beneficial for the cardiological monitoring of breast cancer patients. Methods Patients were followed up with echocardiography at baseline, during, and after the chemotherapy. Conventional echocardiography and multiple speckle tracking imaging parameters including myocardial work index, atrial strain, twist, and automatic EF were investigated. Results A total of 25 patients were recruited. A subset (15/25) exhibited pronounced GLS reduction, associated with decreased EF and altered cardiac mechanics. Patients with unchanged GLS were often hypertensive and on specific medications, in particular angiotensin-converting enzyme inhibitors (ACE inhibitors)/angiotensin II receptor blockers (ARBs), potentially indicating protective effects. Despite stability in other parameters, GLS and EF sensitivity highlight their importance. A strong correlation between manual and automated EF measurement methods was also observed. Conclusion Despite the small sample size, across diverse echocardiography parameters, GLS and EF are primarily affected by chemotherapy. Hypertensive individuals exhibited lower susceptibility to chemotherapy-induced damage, likely attributed to the cardioprotective properties of ACE inhibitors and angiotensin II receptor blockers. A strong correlation between automatic and Simpson-based EF was found., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Leitman et al.)

Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast ( TNNI2 ) and TnI-slow ( TNNI1 ), are predominantly expressed in fast- and slow-twitch myofibers, respectively. TNNI2 variants are a rare cause of arthrogryposis, whereas TNNI1 variants have not been conclusively established to cause skeletal myopathy. We identified recessive loss-of-function TNNI1 variants as well as dominant gain-of-function TNNI1 variants as a cause of muscle disease, each with distinct physiological consequences and disease mechanisms. We identified three families with biallelic TNNI1 variants (F1: p.R14H/c.190-9G>A, F2 and F3: homozygous p.R14C), resulting in loss of function, manifesting with early-onset progressive muscle weakness and rod formation on histology. We also identified two families with a dominantly acting heterozygous TNNI1 variant (F4: p.R174Q and F5: p.K176del), resulting in gain of function, manifesting with muscle cramping, myalgias, and rod formation in F5. In zebrafish, TnI proteins with either of the missense variants (p.R14H; p.R174Q) incorporated into thin filaments. Molecular dynamics simulations suggested that the loss-of-function p.R14H variant decouples TnI from TnC, which was supported by functional studies showing a reduced force response of sarcomeres to submaximal [Ca 2+ ] in patient myofibers. This contractile deficit could be reversed by a slow skeletal muscle troponin activator. In contrast, patient myofibers with the gain-of-function p.R174Q variant showed an increased force to submaximal [Ca 2+ ], which was reversed by the small-molecule drug mavacamten. Our findings demonstrated that TNNI1 variants can cause muscle disease with variant-specific pathomechanisms, manifesting as either a hypo- or a hypercontractile phenotype, suggesting rational therapeutic strategies for each mechanism.

Study Question: Can the BlastAssist deep learning pipeline perform comparably to or outperform human experts and embryologists at measuring interpretable, clinically relevant features of human embryos in IVF?, Summary Answer: The BlastAssist pipeline can measure a comprehensive set of interpretable features of human embryos and either outperform or perform comparably to embryologists and human experts in measuring these features., What Is Known Already: Some studies have applied deep learning and developed 'black-box' algorithms to predict embryo viability directly from microscope images and videos but these lack interpretability and generalizability. Other studies have developed deep learning networks to measure individual features of embryos but fail to conduct careful comparisons to embryologists' performance, which are fundamental to demonstrate the network's effectiveness., Study Design, Size, Duration: We applied the BlastAssist pipeline to 67 043 973 images (32 939 embryos) recorded in the IVF lab from 2012 to 2017 in Tel Aviv Sourasky Medical Center. We first compared the pipeline measurements of individual images/embryos to manual measurements by human experts for sets of features, including: (i) fertilization status (n = 207 embryos), (ii) cell symmetry (n = 109 embryos), (iii) degree of fragmentation (n = 6664 images), and (iv) developmental timing (n = 21 036 images). We then conducted detailed comparisons between pipeline outputs and annotations made by embryologists during routine treatments for features, including: (i) fertilization status (n = 18 922 embryos), (ii) pronuclei (PN) fade time (n = 13 781 embryos), (iii) degree of fragmentation on Day 2 (n = 11 582 embryos), and (iv) time of blastulation (n = 3266 embryos). In addition, we compared the pipeline outputs to the implantation results of 723 single embryo transfer (SET) cycles, and to the live birth results of 3421 embryos transferred in 1801 cycles., Participants/materials, Setting, Methods: In addition to EmbryoScope™ image data, manual embryo grading and annotations, and electronic health record (EHR) data on treatment outcomes were also included. We integrated the deep learning networks we developed for individual features to construct the BlastAssist pipeline. Pearson's χ2 test was used to evaluate the statistical independence of individual features and implantation success. Bayesian statistics was used to evaluate the association of the probability of an embryo resulting in live birth to BlastAssist inputs., Main Results and the Role of Chance: The BlastAssist pipeline integrates five deep learning networks and measures comprehensive, interpretable, and quantitative features in clinical IVF. The pipeline performs similarly or better than manual measurements. For fertilization status, the network performs with very good parameters of specificity and sensitivity (area under the receiver operating characteristics (AUROC) 0.84-0.94). For symmetry score, the pipeline performs comparably to the human expert at both 2-cell (r = 0.71 ± 0.06) and 4-cell stages (r = 0.77 ± 0.07). For degree of fragmentation, the pipeline (acc = 69.4%) slightly under-performs compared to human experts (acc = 73.8%). For developmental timing, the pipeline (acc = 90.0%) performs similarly to human experts (acc = 91.4%). There is also strong agreement between pipeline outputs and annotations made by embryologists during routine treatments. For fertilization status, the pipeline and embryologists strongly agree (acc = 79.6%), and there is strong correlation between the two measurements (r = 0.683). For degree of fragmentation, the pipeline and embryologists mostly agree (acc = 55.4%), and there is also strong correlation between the two measurements (r = 0.648). For both PN fade time (r = 0.787) and time of blastulation (r = 0.887), there's strong correlation between the pipeline and embryologists. For SET cycles, 2-cell time (P < 0.01) and 2-cell symmetry (P < 0.03) are significantly correlated with implantation success rate, while other features showed correlations with implantation success without statistical significance. In addition, 2-cell time (P < 5 × 10-11), PN fade time (P < 5 × 10-10), degree of fragmentation on Day 3 (P < 5 × 10-4), and 2-cell symmetry (P < 5 × 10-3) showed statistically significant correlation with the probability of the transferred embryo resulting in live birth., Limitations, Reasons for Caution: We have not tested the BlastAssist pipeline on data from other clinics or other time-lapse microscopy (TLM) systems. The association study we conducted with live birth results do not take into account confounding variables, which will be necessary to construct an embryo selection algorithm. Randomized controlled trials (RCT) will be necessary to determine whether the pipeline can improve success rates in clinical IVF., Wider Implications of the Findings: BlastAssist provides a comprehensive and holistic means of evaluating human embryos. Instead of using a black-box algorithm, BlastAssist outputs meaningful measurements of embryos that can be interpreted and corroborated by embryologists, which is crucial in clinical decision making. Furthermore, the unprecedentedly large dataset generated by BlastAssist measurements can be used as a powerful resource for further research in human embryology and IVF., Study Funding/competing Interest(s): This work was supported by Harvard Quantitative Biology Initiative, the NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard (award number 1764269), the National Institute of Heath (award number R01HD104969), the Perelson Fund, and the Sagol fund for embryos and stem cells as part of the Sagol Network. The authors declare no competing interests., Trial Registration Number: Not applicable., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The article focuses on the professional quality of life of medical residents, and specifically on compassion fatigue and compassion satisfaction. Previous studies have indicated high levels of emotional stress among residents. Most of these studies were conducted within the positivistic paradigm. The qualitative study concentrates on pediatric residents during ER rotations in both routine and pandemic times., Aims: The research goal is to explore how compassion fatigue and compassion satisfaction are manifested among the residents., Methods: Conducted in the phenomenological genre, the study included 14 pediatric residents in a large Israeli hospital. The research tool was a semi-structured interview., Results: All residents reported substantial work overloads. About half of the participants indicated signs of compassion fatigue, manifested in negative emotions and diminished empathy and sensitivity, especially towards patients' families. Some exhibited a combination of compassion fatigue and compassion satisfaction. About half of the residents clearly expressed feelings of compassion satisfaction or empathy for patients (without direct expressions of compassion satisfaction)., Conclusions: The research gave pediatric residents a platform to express their voices, shedding light on the complexity of their work. While a substantial number of participants reported compassion fatigue, the findings are encouraging. Despite the reported work overload, most of them maintained their sense of commitment and compassion, which are crucial for their work. However, participants' senses of stress and burnout have negative consequences both individually and organizationally. The study suggests that residents might gain from systematic intervention and recommendations have been offered to hospital administrations.

Unconscious processing has been widely examined using diverse and well-controlled methodologies. However, the extent to which these findings are relevant to real-life instances of information processing without awareness is limited. Here, we present a novel inattentional blindness (IB) paradigm in virtual reality (VR). In three experiments, we managed to repeatedly induce IB while participants foveally viewed salient stimuli for prolonged durations. The effectiveness of this paradigm demonstrates the close relationship between top-down attention and subjective experience. Thus, this method provides an ecologically valid setup to examine processing without awareness., (© 2024. The Author(s).)

Background: This study challenges the prevalent belief that surgical roles demand masculine traits, potentially limiting women's suitability for such positions. Contrary to this stereotype, we explored the hypothesis that in sensitive surgical procedures, where communal traits are valued, women patients might favor women surgeons. Two experimental studies investigated women's preferences for a man versus a woman surgeon in a breast exam and breast surgery., Methods: In two studies we experimentally tested women's preferences for a man versus a woman surgeon for a breast exam (a noninvasive and non-complicated procedure), and breast surgery (an invasive and more complicated procedure). Study 2 delved into factors influencing these preferences, including patients' age, stereotypical perceptions of women surgeons as communal/warm, past negative experiences with men and women doctors, and previous body-related trauma., Results: Women consistently preferred a woman surgeon for both procedures and expressed increased willingness to wait for an appointment with a woman surgeon. However, this preference was less pronounced for surgery than for an exam. Study 2 identified the stereotypical perception of women surgeons as communal/warm as the strongest predictor for this preference, along with previous negative experiences with men doctors and age., Conclusions: While some gender bias persists, this study underscores a notable preference for women surgeons in intimate medical services like breast exams or surgery. This preference holds practical implications for healthcare providers encouraging women's preventive checkups and offers insights for women medical students making residency choices., (© 2024 The Authors. World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Participation restrictions following traumatic brain injury are associated with executive function (EF) deficits (EFDs). The subacute recovery phase's specific characteristics (enhanced brain plasticity and impaired self-awareness) and contextual factors (inpatient setting) warrant adjusting cognitive rehabilitation protocols. The Intervention of Participation and Executive Functions (I-PEX) was designed to improve EFDs during subacute inpatient rehabilitation., Objective: To investigate the I-PEX's preliminary efficacy to improve EFDs during the performance of complex daily activities and enhance self-awareness, cognitive self-efficacy, participation, and quality of life postdischarge., Methods: A pilot pre-, post-, and follow-up double-blind randomized controlled trial with 25 participants randomly allocated to the I-PEX (n = 13) or treatment-as-usual (n = 12) group. Cognitive assessments were administered pre- and postintervention, and quality of life and participation questionnaires 1-month postdischarge. Data analysis included repeated measures analysis of variance mixed design and independent t -tests, extracting effect sizes., Results: Significant group-by-time interaction effect with a medium effect size was found for the primary outcome measure; EFs manifested in complex daily activities, indicating a larger improvement for the experimental group. The group effect was not significant. The experimental group's mean delta score (pre-post improvement) was significantly higher (1.75 ± 2.89; t (23)  = 2.52, P  = .019), with a large effect size ( d  = 1.012, 95% confidence interval [0.166-1.840]). We found no significant group and interaction effects for EFs, self-awareness, and cognitive self-efficacy or no significant differences in participation or quality of life postdischarge., Conclusions: Results provide initial evidence for the I-PEX efficacy in treating EFDs in the subacute phase and could help determine effect size for future studies., Clinical Trial Registry Number: ClinicalTrial.gov NCT04292925., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the association between a topical hemostatic agent used at the time of cesarean delivery and uterine scar disruption (rupture or dehiscence) at the subsequent trial of labor after cesarean (TOLAC)., Methods: A multicenter retrospective cohort study was conducted (2005-2021). Parturients with a singleton pregnancy in whom a topical hemostatic agent was placed during the primary cesarean delivery were compared with patients in whom no such agent was placed. We assessed the uterine scar disruption rate after the subsequent TOLAC and the rate of adverse maternal outcomes. Univariate analyses were followed by multivariate analysis (adjusted odds ratio [aOR]; 95% confidence interval [CI])., Results: During the study period, 7199 women underwent a trial of labor and were eligible for the study; 430 (6.0%) had prior use of a hemostatic agent, 6769 (94.0%) did not. In univariate analysis, a history of topical hemostatic agent use was not found to be significantly associated with uterine scar rupture, dehiscence, or failed trial of labor. This was also confirmed on multivariate analysis for uterine rupture (aOR 1.91, 95% CI 0.66-5.54; P = 0.23), dehiscence of uterine scar (aOR 1.62, 95% CI 0.56-4.68; P = 0.37), and TOLAC failure (aOR 1.08, 95% CI 0.79-1.48; P = 0.61)., Conclusion: A history of hemostatic agent use is not associated with an increased risk for uterine scar disruption after subsequent TOLAC. Further prospective studies in other settings are needed to strengthen these findings., (© 2023 International Federation of Gynecology and Obstetrics.)

Electrocatalytic alcohol oxidation in acid offers a promising alternative to the kinetically sluggish water oxidation reaction toward low-energy H 2 generation. However, electrocatalysts driving active and selective acidic alcohol electrochemical transformation are still scarce. In this work, we demonstrate efficient alcohol-to-aldehyde conversion achieved by reticular chemistry-based modification of the catalyst's immediate environment. Specifically, coating a Bi-based electrocatalyst with a thin layer of metal-organic framework (MOF) substantially improves its performance toward benzyl alcohol electro-oxidation to benzaldehyde in a 0.1 M H 2 SO 4 electrolyte. Detailed analysis reveals that the MOF adlayer influences catalysis by increasing the reactivity of surface hydroxides as well as weakening the catalyst-benzaldehyde binding strength. In turn, low-potential (0.65 V) cathodic H 2 evolution was obtained through coupling it with anodic benzyl alcohol electro-oxidation. Consequently, the presented approach could be implemented in a wide range of electrocatalytic oxidation reactions for energy-conversion application., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Infants suffering from lower respiratory tract infections (LRTIs) have distinct nasopharyngeal (NP) microbiome profiles that correlate with severity of disease. Whether these profiles precede the infection or are a consequence of it, is unknown. In order to answer this question, longitudinal studies are needed., Methods: We conducted a retrospective analysis of NP samples collected in a longitudinal birth cohort study of Zambian mother-infant pairs. Samples were collected every two weeks from 1-week through 14-weeks of age. Ten of the infants in the cohort who developed LRTI were matched 1:3 with healthy comparators. We completed 16S rRNA gene sequencing on the samples each of these infants contributed and compared the NP microbiome of the healthy infants to infants who developed LRTI., Results: The infant NP microbiome maturation was characterized by transitioning from Staphylococcus dominant to respiratory-genera dominant profiles during the first three months of life, similar to what is described in the literature. Interestingly, infants who developed LRTI had distinct NP microbiome characteristics before infection, in most cases as early as the first week of life. Their NP microbiome was characterized by the presence of Novosphingobium, Delftia , high relative abundance of Anaerobacillus, Bacillus , and low relative abundance of Dolosigranulum, compared to the healthy controls. Mothers of infants with LRTI also had low relative abundance of Dolosigranulum in their baseline samples compared to mothers of infants that did not develop an LRTI., Conclusions: Our results suggest that specific characteristics of the NP microbiome precede LRTI in young infants and may be present in their mothers as well. Early dysbiosis may play a role in the causal pathway leading to LRTI or could be a marker of underlying immunological, environmental, or genetic characteristics that predispose to LRTI., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Lapidot R et al.)

The ability of an animal to effectively capture prey and defend against predators is pivotal for survival. Venom is often a mixture of many components including toxin proteins that shape predator-prey interactions. Here, we used the sea anemone Nematostella vectensis to test the impact of toxin genotypes on predator-prey interactions. We developed a genetic manipulation technique to demonstrate that both transgenically deficient and a native Nematostella strain lacking a major neurotoxin (Nv1) have a reduced ability to defend themselves against grass shrimp, a native predator. In addition, secreted Nv1 can act indirectly in defense by attracting mummichog fish, which prey on grass shrimp. Here, we provide evidence at the molecular level of an animal-specific tritrophic interaction between a prey, its antagonist, and a predator. Last, this study reveals an evolutionary trade-off, as the reduction of Nv1 levels allows for faster growth and increased reproductive rates.

Introduction Pre exposure prophylaxis with monoclonal antibodies (mAbs) were developed in addition to COVID19 vaccine for immunocompromised and those with insufficient immune response, among them patients with CLL. Omicron variant and its sublineages evolved mutations that escape mAbs neutralizing effect, yet the extent of which was not studied. Methods We evaluated anti-spike titters and neutralization activity of COVID-19 wild type (WT) , Delta , Omicron, BA2, BA4 and BA5 before and after tixagevimab-cilgavimab (TGM/CGM) dose of 150/150mg or 300/300mg in patients with CLL. Results 70 patients were tested 2 weeks before and 4 weeks after receiving TGM/CGM mAbs. After TGM/CGM anti-spike ab level increased 170 folds from 13.6 BAU/ml (IQR, 0.4-288) to 2328 BAU/ml (IQR, 1681-3500). Neutralization activity increased in all variants, and was 176 folds higher in WT and 55 folds higher in Delta compared to 10 folds higher in Omicron and its sublineages (BA2 x11, BA4 x4 , BA5 x18). Over follow-up period of 3 months, 20 patients (29%) with CLL acquired COVID-19 infection, all recovered uneventfully. In a multivariate analysis anti-spike antibody titer was found a significant predictor for post TGM/CGM COVID19 infection. Conclusion Efficacy of preexposure prophylaxis with TGM/CGM in patients with CLL is significantly reduced in era of Omicron and its sublineages BA2, BA4 and BA5., (The Author(s). Published by S. Karger AG, Basel.)

Endothelial microvascular dysfunction affects multi-organ pathologic processes that contribute to increased vascular tone and is at the base of impaired metabolic and cardiovascular diseases. The vascular dilation impaired by nitric oxide (NO) deficiency in such dysfunctional endothelium is often balanced by endothelial-derived hyperpolarizing factors (EDHFs), which play a critical role in managing vascular tone. Our latest research has uncovered a new group of lactone oxylipins produced in the polyunsaturated fatty acids (PUFAs) CYP450 epoxygenase pathway, significantly affecting vascular dilation. The lactone oxylipin, derived from arachidonic acid (5,6-diHET lactone, AA-L), has been previously shown to facilitate vasodilation dependent on the endothelium in isolated human microvessels. The administration of the lactone oxylipin derived from eicosapentaenoic acid (5,6-diHETE lactone, EPA-L) to hypertensive rats demonstrated a significant decrease in blood pressure and improvement in the relaxation of microvessels. However, the molecular signaling processes that underlie these observations were not fully understood. The current study delineates the molecular pathways through which EPA-L promotes endothelium-dependent vascular dilation. In microvessels from hypertensive individuals, it was found that EPA-L mediates endothelium-dependent vasodilation while the signaling pathway was not dependent on NO. In vitro studies on human endothelial cells showed that the hyperpolarization mediated by EPA-L relies on G-protein-coupled receptor (GPR)-phospholipase C (PLC)-IP3 signaling that further activates calcium-dependent potassium flux. The pathway was confirmed using a range of inhibitors and cells overexpressing GPR40, where a specific antagonist reduced the calcium levels and outward currents induced by EPA-L. The downstream AKT and endothelial NO synthase (eNOS) phosphorylations were non-significant. These findings show that the GPR-PLC-IP3 pathway is a key mediator in the EPA-L-triggered vasodilation of arterioles. Therefore, EPA-L is identified as a significant lactone-based PUFA metabolite that contributes to endothelial and vascular health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrea Szuchman Sapir reports financial support, equipment, drugs, or supplies, and travel were provided by Migal Galilee Technology Center. Andrea Szuchman Sapir has patent #5,6-DIHETE LACTONE FOR TREATMENT OF MICROVASCULAR DYSFUNCTION pending to 17/615,670. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Andrea Szuchman Sapir reports financial support, equipment, drugs, or supplies, and travel were provided by Migal Galilee Technology Center. Andrea Szuchman Sapir has patent #5,6-DIHETE LACTONE FOR TREATMENT OF MICROVASCULAR DYSFUNCTION pending to 17/615,670. If there are other authors, they 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 Inc. All rights reserved.)

Numerous studies have identified traveling waves in the cortex and suggested they play important roles in brain processing. These waves are most often measured using macroscopic methods that are unable to assess the local spiking activity underlying wave dynamics. Here, we investigated the possibility that waves may not be traveling at the single neuron scale. We first show that sequentially activating two discrete brain areas can appear as traveling waves in EEG simulations. We next reproduce these results using an analytical model of two sequentially activated regions. Using this model, we were able to generate wave-like activity with variable directions, velocities, and spatial patterns, and to map the discriminability limits between traveling waves and modular sequential activations. Finally, we investigated the link between field potentials and single neuron excitability using large-scale measurements from turtle cortex ex vivo. We found that while field potentials exhibit wave-like dynamics, the underlying spiking activity was better described by consecutively activated spatially adjacent groups of neurons. Taken together, this study suggests caution when interpreting phase delay measurements as continuously propagating wavefronts in two different spatial scales. A careful distinction between modular and wave excitability profiles across scales will be critical for understanding the nature of cortical computations., Competing Interests: YO, AR, RP, YL, PB, MS No competing interests declared, (© 2023, Orsher et al.)

Background: GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%-13% 5-year survival. Most human GBMs manifest as immunologically "cold" tumors or "immune deserts," yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate., Methods: We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by "digital cytometry." The FC-derived data were combined with the patients' demographic, clinical, molecular, histopathological, radiological, and survival data., Results: Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas' pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort)., Conclusions: The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We studied the extent of carbapenemase-producing Enterobacteriaceae (CPE) sink contamination and transmission to patients in a nonoutbreak setting., Methods: During 2017-2019, 592 patient-room sinks were sampled in 34 departments. Patient weekly rectal swab CPE surveillance was universally performed. Repeated sink sampling was conducted in 9 departments. Isolates from patients and sinks were characterized using pulsed-field gel electrophoresis (PFGE), and pairs of high resemblance were sequenced by Oxford Nanopore and Illumina. Hybrid assembly was used to fully assemble plasmids, which are shared between paired isolates., Results: In total, 144 (24%) of 592 CPE-contaminated sinks were detected in 25 of 34 departments. Repeated sampling (n = 7,123) revealed that 52%-100% were contaminated at least once during the sampling period. Persistent contamination for >1 year by a dominant strain was common. During the study period, 318 patients acquired CPE. The most common species were Klebsiella pneumoniae , Escherichia coli , and Enterobacter spp. In 127 (40%) patients, a contaminated sink was the suspected source of CPE acquisition. For 20 cases with an identical sink-patient strain, temporal relation suggested sink-to-patient transmission. Hybrid assembly of specific sink-patient isolates revealed that shared plasmids were structurally identical, and SNP differences between shared pairs, along with signatures for potential recombination events, suggests recent sharing of the plasmids., Conclusions: CPE-contaminated sinks are an important source of transmission to patients. Although traditionally person-to-person transmission has been considered the main route of CPE transmission, these data suggest a change in paradigm that may influence strategies of preventing CPE dissemination.

Background: Obliterative vaginal procedures may offer lower perioperative morbidity and equal success rates as reconstructive procedures for frail and elderly women who no longer desire future coital function. The combination of vaginal hysterectomy with either reconstructive or obliterative vaginal procedures has not yet been investigated., Objectives: To compare peri- and postoperative outcomes of vaginal hysterectomy with pelvic floor reconstruction (VHR) vs. vaginal hysterectomy with colpocleisis (VHC)., Methods: We conducted a retrospective study comparing medical and surgical data of patients undergoing either VHR or VHC between 2006 and 2015. Data were obtained from inpatient and outpatient medical records including peri- and postoperative course, as well as long-term (24 months) follow-up data., Results: We identified 172 patients who underwent VHR and 44 who underwent VHC. Patients in the VHC group were significantly older (71.3 ± 4.5 vs. 68.6 ± 6.5 years, P = 0.01), and more likely to have medical co-morbidities (P = 0.001 and P = 0.029, respectively). Patients in the VHC group experienced shorter operative time (2.3 ± 0.58 vs. 2.7 ± 1.02 hours, P = 0.007), lower perioperative blood loss (P < 0.0001), shorter hospital stay (P < 0.0001), and lower rates of postoperative urinary retention. Long-term pelvic organ prolapse (POP) recurrence rates were significantly higher among the VHR group. Postoperative resolution of both stress urinary incontinence and overactive bladder were common in both groups., Conclusions: VHC is associated with lower perioperative blood loss, shorter operative time, shorter hospital stay, shorter time with an indwelling catheter, and lower long-term objective POP recurrence rates.

Background: Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE., Methods: We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I 2  > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively., Results: Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I 2  = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I 2  = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I 2  = 50%; RR 0.58, 95% CI 0.50-0.67, I 2  = 7%; RR 0.64, 95% CI 0.59-0.70, I 2  = 0%, respectively)., Conclusions: Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aggressive behavior among adolescents has been identified as a serious worldwide problem, especially when combined with trait impulsivity. This study investigates the impact of an overlooked aspect of language, namely, metaphor comprehension, on impulsivity and aggression in adolescents. A total of 204 adolescents completed self-reported questionnaires assessing impulsivity and aggression and underwent tests assessing familiar and less familiar metaphor comprehension. The findings reveal inverse relationships between metaphor comprehension and both impulsivity and aggression. Regarding aggression, notable distinctions were observed in the correlations between familiar and less familiar metaphors with specific aggression types. Additionally, impulsivity was found to mediate the relationship between the comprehension of familiar metaphors and aggression. These results are elucidated in the context of cognitive and executive functions, emphasizing the significance of considering metaphor comprehension as a cognitive process capable of modulating aggressive behavior., Competing Interests: Declaration of competing interest The author(s) declare none., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)