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Background: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear. Objective: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status. Methods: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow‐up cognitive screening scores were analyzed. Results: GBA1 mutation carriers had a two‐fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly. Conclusion: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials. [ABSTRACT FROM AUTHOR]

High‐performance polycrystalline calcium cobaltite ceramic was synthesized via electrospinning of nanoribbons, followed by dual‐process compaction using spark plasma sintering and edge‐free spark plasma texturing. The combination of nanoribbon electrospinning and this multistage sintering technique was employed for the first time and resulted in exceptionally well‐textured thermoelectric ceramics. The textured ceramic had excellent thermoelectric properties. At 1073 K, the ceramic exhibited an electrical conductivity of 268 S cm−1, a Seebeck coefficient of 247 µV K−1 and a heat conductivity of 3.3 W m−1 K−1. In addition, the power factor and figure‐of‐merit reached enormously high values of 16.3 µW cm−1 K−2 and 0.53, respectively. This represents the highest thermoelectric performance reported to date not only for electrospun, polycrystalline calcium cobaltite fiber ceramics, but also for undoped polycrystalline calcium cobaltite ceramics. [ABSTRACT FROM AUTHOR]

This paper conceptualizes the phenomenon of historizing the present, defined as emphasizing the historical significance of present events and treating the present from the perspective of history. The authors identify four modes of historizing the present (emphasizing that: (1) the present will shape history; (2) the present is a unique moment in history; (3) the present will be remembered in history; (4) the present echoes history) and demonstrate how historizing can be employed by marketers of for‐profit and nonprofit organizations in a variety of contexts. The paper examines the psychological implications of appreciating the historical significance of the present and outlines a research agenda for studying the downstream behavioral consequences of historizing the present across diverse substantive consumer domains. It concludes with an examination of the broader societal implications of historizing the present as well as its implications for consumer well‐being. [ABSTRACT FROM AUTHOR]

Misfit‐layered calcium cobaltite [Ca2CoO3‐δ]0.62[CoO2] is an outstanding p‐type semiconducting thermoelectric with strong anisotropic properties. Texture engineering is crucial for enhancing its thermoelectric performance in polycrystalline ceramics. The in‐plane orientation of the grains improves the Seebeck coefficient and electrical conductivity, while the multi‐scale parallel interfaces scatter phonons and reduce thermal conductivity. Here, a tandem process of spark plasma sintering and edge‐free spark plasma texturing is used to produce dense and highly textured calcium cobaltite ceramics. The resulting ceramic shows a high degree of texturization, secondary phases, and enhanced electrical conductivity of 246 S cm−1 together with a strongly improved Seebeck coefficient of 224 µV K−1 at 1073 K. High grain ordering leads to carrier mobility of 0.49 cm2 V−1 s−1, which has a positive effect on both parameters. With a power factor of 12.4 µW cm−1 K−2 at 1073 K in air, previous thermoelectric performances of calcium cobaltite are surpassed, regardless of its form: pristine, doped, or composite. By combining the high power factor with a relatively low thermal conductivity, a remarkable figure‐of‐merit of 0.49 at 1073 K in air is obtained for the textured polycrystalline ceramic, which reaches 60 % of the figure‐of‐merit of a calcium cobaltite single crystal. [ABSTRACT FROM AUTHOR]

Summary Changes in chromosome numbers are a prominent driver of plant evolution, impacting ecological diversification, stress tolerance, and phenotypes. ChromEvol is a widely used software tool for deciphering patterns of chromosome‐number change along a phylogeny of interest. It evaluates the fit of alternative models to the data, estimates transition rates of different types of events, and infers the expected number of events along each branch of the phylogeny. We introduce ChromEvol v.3, featuring multiple novel methodological advancements that capture variation in the transition rates along a phylogeny. This version better allows researchers to identify how dysploidy and polyploidy rates change based on the number of chromosomes in the genome, with respect to a discrete trait, or at certain subclades of the phylogeny. We demonstrate the applicability of the new models on the Solanaceae phylogeny. Our analyses identify four chromosome‐number transition regimes that characterize distinct Solanaceae clades and demonstrate an association between self‐compatibility and altered dynamics of chromosome‐number evolution. ChromEvol v.3, available at https://github.com/anatshafir1/chromevol, offers researchers a more flexible, comprehensive, and accurate tool to investigate the evolution of chromosome numbers and the various processes affecting it. [ABSTRACT FROM AUTHOR]

Exposure to conflict‐related violence is one of the most harmful consequences of living amidst a violent intergroup conflict. While its potential significance is profound, the impact of exposure to conflict‐related violence on intergroup empathy remains largely unexplored. The current paper aims to address this gap by proposing political ideology as a potential moderator of the exposure‐empathy link. Three studies conducted among Jewish‐Israeli participants reveal an interactive effect of exposure to conflict‐related violence and political ideology on intergroup empathy. In Study 1, high (vs. low) exposure to conflict‐related violence was associated with decreased empathy among rightists—but increased empathy among leftists—towards individual outgroup members. In Study 2, political ideology also moderated the exposure‐empathy relationship: Bereaved (vs. non‐bereaved) rightists exhibited significantly less intergroup empathy towards both an individual bereaved outgroup member and the outgroup as a whole, an effect not found among leftists. Study 3 revealed a similar, albeit marginally significant, interactive effect of exposure to conflict‐related violence and political ideology on empathy towards individuals living in a different violent conflict. Finally, an internal meta‐analysis provided further, more robust evidence for these effects. We discuss theoretical and practical implications of the findings and suggest future directions for research on this important issue. [ABSTRACT FROM AUTHOR]

Summary: Obstructive sleep apnea is a prevalent sleep‐disordered breathing condition characterized by repetitive reduction in breathing during sleep. The current care standard for obstructive sleep apnea is continuous positive air pressure devices, often suffering from low tolerance due to limited adherence. Capitalizing on the unique neurocircuitry of olfactory perception and its retained function during sleep, we conducted a pilot study to test transient, respiration‐based olfactory stimulation as a treatment for obstructive sleep apnea markers. Thirty‐two patients with obstructive sleep apnea (apnea–hypopnea index ≥ 15 events per hr) underwent two polysomnography sessions, "Odour" and "Control", in random order. In "Odour" nights, patients were presented with transient respiratory‐based olfactory stimulation delivered via a computer‐controlled commercial olfactometer (Scentific). The olfactometer, equipped with a wireless monitoring, analysed respiratory patterns and presented odour upon detection of respiratory events. No odours were presented in "Control" nights. Following exclusions, 17 patients entered the analysis (four women, 47.4 (10.5) years, body mass index: 29.4 (6.3) kg m−2). We observed that olfactory stimulation during sleep reduced the apnea–hypopnea index ("Odour": 17.2 (20.9), "Control": 28.2 (18.6), z = −3.337, p = 0.000846, BF10 [Bayesian Factor 10]= 57.9), reflecting an average decrease of 31.3% in the number of events. Relatedly, stimulation reduced the oxygen desaturation index by 26.9% ("Odour": 12.5 (15.8), "Control": 25.7 (25.9), z = −3.337, p = 0.000846, BF10 = 9.522). This effect was not linked to the severity of baseline obstructive sleep apnea markers (ρ = −0.042, p = 0.87). Olfactory stimulation did not arouse from sleep or affect sleep structure, measured as time per sleep stage (F1,16 = 0.088, p = 0.77). In conclusion, olfactory stimulation during sleep was effective in reducing the severity of obstructive sleep apnea markers without inducing arousals, and may provide a novel treatment for obstructive sleep apnea, prompting continued research. [ABSTRACT FROM AUTHOR]

Background: Peripheral nodal B‐cell lymphomas (PNBCL) represent the most common presentation of lymphomas in dogs. Multiagent CHOP (C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone)‐based chemotherapy protocols have been widely accepted as gold standard 1st‐line treatment. CHOP‐25 and CHOP‐19 are most commonly prescribed but have never been directly compared. Objectives: Our primary aim was to compare outcomes of dogs diagnosed with PNBCL, treated using a 1st‐line CHOP‐19 or CHOP‐25 protocol. A secondary objective was to determine the impact of protocol‐related variables on outcomes. Animals: Five hundred two dogs from 16 European oncology referral centers. One hundred fifty‐five dogs were treated with CHOP‐19 and 347 dogs with CHOP‐25. Methods: Retrospective, multicentric cohort study of dogs diagnosed with PNBCL between 2014 and 2021. Results: The 6‐month, 1‐year, and median progression‐free survival (PFS) were 56.5% (95% confidence interval [CI], 49.2‐65.0), 14.1% (95% CI, 9.4‐21.0), and 196 days (95% CI, 176‐233) with CHOP‐19; and 56.4% (95% CI, 51.4‐61.9), 17% (95% CI, 13.4‐21.6), and 209 days (95% CI, 187‐224) with CHOP‐25. The 1‐year, 2‐year and median overall survival (OS) were 36.9% (95% CI, 29.7‐46.0), 13.5% (95% CI, 8.6‐21.1), and 302 days (95% CI, 249‐338) with CHOP‐19; and 42.8% (95% CI, 37.7‐48.7), 15.4% (95% CI, 11.7‐20.4), and 321 days (95% CI, 293‐357) with CHOP‐25. No significant difference in PFS and OS was found between the 2 protocols. Conclusions and Clinical Importance: Our study confirmed similar outcomes for dogs with PNBCL treated with 1st‐line CHOP‐19 or CHOP‐25. Both protocols therefore could be used as a standard of care in future trials. [ABSTRACT FROM AUTHOR]

Social participation in school, including schoolyard interactions, is considered important for all aspects of child development. Students with disabilities, such as those who are deaf and hard‐of‐hearing, are at risk of experiencing inaccessibility and social exclusion in mainstream classes, yet this has been hardly researched in the schoolyard context. We exploratively compared preadolescents (M = 10.48, SD =.93) with (N = 8) and without (N = 207) hearing loss in their continuous schoolyard interactions during 21 recess assessments, using proximity sensors and field observations, alongside measurements of peer acceptance, friendships and sense of connectedness, based on peer nominations and self‐reports. Deaf and hard‐of‐hearing preadolescents spent less time interacting in the schoolyard, a trend which was stable throughout recess. Deaf and hard‐of‐hearing students interacted with the same number of partners as their classmates, but posthoc analyses suggest that towards the end of long recess periods they had a sharper drop in the number of their interaction partners. Field observations suggest that deaf and hard‐of‐hearing preadolescents who were socially active became more isolated the longer the break lasted, and that physical proximity did not necessarily indicate positive interactions. Findings underscore the importance of using multimethod designs that assess various dimensions of social participation and account for the temporal dynamics of recess interactions. Proximity sensors, combined with qualitative observations, enabled to detect social difficulties not detected by more traditional measures, hence valuable for social inclusion research and interventions. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Conclusions Personal values and personality traits are both important aspects of personality, but much is still unknown about the fundamental differences between the constructs, including how their patterns of temporal stability compare. This paper investigated patterns of intra‐individual stability in both values and traits.Quantile correlations were estimated between each of the 20 refined personal values and the same values 2 years later in a large longitudinal sample of Australian adults (N = 2875). The same was done for each of the 15 Five‐Factor Model trait facets in a subsample of these participants (n = 2424).It was observed that more important values tended to remain more stable over time, while traits retained a similar stability regardless of trait strength, and frequently showed small decreases in stability at extreme levels.Findings indicate that highly prioritized values may be a more central aspect of the self, and a more reliable element for predicting future outcomes, than less highly prioritized values, but in contrast, traits do not function in a way that is dependent on trait strength. [ABSTRACT FROM AUTHOR]

Street‐level organizations (SLOs) play a key, but understudied, political role in democratic governance as they are responsible for the direct‐delivery of public services that are vital to the functioning of the state. To discuss the political role of SLOs in general, this study begins by identifying four SLO roles, which are conceptualized here by distinguishing policy‐sphere versus politics‐sphere and "SLOs‐as‐takers" versus "SLOs‐as‐makers." SLOs' political role in a democratic backsliding and populism context is specified by distinguishing whether SLOs converge to, or diverge from, illiberal policies, and distinguishing reactive and proactive responses. Each of the four responses is elaborated by referring to how SLOs both influence, and are influenced by, populism and democratic backsliding. Shifting attention to the specific context of democratic erosion allows a more nuanced distinction between policy sectors and countries, as well as identifying the ways through which public service provision facilitates or inhibits democratic backsliding. [ABSTRACT FROM AUTHOR]

Summary: Background: There is a scarcity of published studies evaluating transgender/gender‐diverse youth before initiating gender‐affirming hormones. Aim: To study the body composition, metabolic syndrome (MetS) components and lifestyle habits in treatment‐naïve transgender youth. Methods: Cross‐sectional study evaluating 153 transgender youth [median age 15.7 years, 94 transgender males] who attended The Israeli Children and Adolescents Gender Clinic between 6/2021–12/2022. Clinical, metabolic data and lifestyle habits (diet, physical activity and sleep patterns) were retrieved from the medical files. Body composition was determined by bioelectrical impedance analysis. Body mass index and muscle‐to‐fat ratio z‐scores were calculated by sex designated at birth. Results: Weight categories differed between genders, with a greater proportion of subjects classified as underweight among transgender females, and a greater proportion affected by overweight/obese/severe obese among transgender males (p = 0.035). The odds for MetS components were increased by 2.2 for every 1 standard deviation decrease in the muscle‐to‐fat ratio z‐score (95%CI: 1.45 to 3.26, p < 0.001). About one‐third of the cohort did not meet any of the three lifestyle recommendations. Transgender males had increased odds for MetS components by 3.49 (95%CI: 1.63 to 7.44, p = 0.001). Conclusions: Treatment‐naïve transgender‐male adolescents have an imbalance between muscle and adipose tissue, which places them at increased susceptibility for MetS components even prior to hormonal treatment. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate value change and stability longitudinally in middle childhood. Background: Values are the aspect of personality defining one's aspirations. Research identifies meaningful values in middle childhood, yet we know little about the process of their development within individual. Method: Children (N = 298; 53.7% girls, Mage = 7 years and 3 months, SD = 7.70 months, at the first time point) four times, annually. Results: Rank‐order stability increased with age and decreased with time‐span. We found value hierarchy consistency, with value hierarchy similar to adolescents in the priority given to openness to change versus conservation values, and to adults in the priority given to self‐transcendence values. Latent growth curve analyses indicated linear increase in openness to change, and curvilinear increase in self‐transcendence values, and linear decrease in conservation and self‐enhancement values, with some differences across ages. Value structure was better differentiated with age. Compatible values changed in similar, and conflicting values in opposite directions. Conclusions: This paper suggests that in middle childhood, children can already report stable values. Moreover, middle childhood is characterized by coherent change patterns, of increase in the importance of growth, and decrease in the focus on conflicting protection values. [ABSTRACT FROM AUTHOR]

Background: This study compares patient‐reported functional and aesthetic outcomes of split‐thickness skin graft (STSG) versus hatchet flap closure of radial forearm free flap (RFFF) donor site. Methods: Patients with RFFF (2015–2020) were retrospectively identified. Those willing to participate in patient‐reported outcomes (PRO) filled out Patient‐Observer Scar Assessment Scale (POSAS) and Michigan Hand Outcome Questionnaire (MHOQ). Results: 198 patients met our inclusion criteria and 81 participated in PRO. There was a higher rate of tendon exposure in STSG versus hatchet flap (11 vs. 1, p = 0.0019), but a lower rate of skin necrosis (5 vs. 16, p = 0.0190) and epidermolysis (1 vs. 12, p = 0.0028). Scar quality in STSG was superior to hatchet flap in all domains of POSAS. MHOQ scores were similar between both groups with no statistical difference in overall scores (p = 0.2165). Conclusions: STSG appeared to have less compromise in activities of daily living, better satisfaction and improved scar quality than hatchet flap, but a higher rate of tendon exposure. Level of Evidence: 3 Laryngoscope, 134:4266–4273, 2024 [ABSTRACT FROM AUTHOR]

Aim: To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D). Methods: In a 4‐week, randomized crossover‐controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%‐8.5%) from two sites in Israel. Participants were randomized to drink Mankai (200 mL of raw‐fresh‐aquatic plant + 100 mL of water, 40 kcal, ~10 g of dry matter equivalent) or water (300 mL) following dinner, for 2 weeks each, with a 4‐day washout interval, without dietary, physical activity or pharmacotherapy alterations. We used continuous glucose monitoring (CGM) devices. Results: Forty patients (adherence rate = 88.5%; 743 person‐intervention‐days, 68.9% men, age = 64 years, HbA1c = 6.8%) completed the study with a consistent diet and complete CGM reads. Only two‐thirds of the individuals responded beneficially to Mankai. Overall, Mankai significantly lowered the PG peak by 19.3% (∆peak = 24.3 ± 16.8 vs. 30.1 ± 18.5 mg/dL; P <.001) and delayed the time‐to‐peak by 20.0% (112.5 [interquartile range: 75‐135] vs. 90 [60‐105] min; P <.001) compared with water. The PG incline and decline slopes were shallower following postdinner Mankai (incline slope: 16.8 vs. water: 29.9 mg/[dL h]; P <.001; decline slope: −6.1 vs. water: −7.9 mg/[dL h]; P <.01). Mean postprandial net incremental area‐under‐the‐glucose‐curve was lowered by 20.1% with Mankai compared with water (P =.03). Results were consistent across several sensitivity and subgroup analyses, including across antidiabetic pharmacotherapy treatment groups. Within 2 weeks, the triglycerides/high‐density lipoprotein cholesterol ratio in the Mankai group (−0.5 ± 1.3) decreased versus water (+0.3 ± 1.5, P =.05). Conclusions: Mankai consumption may mitigate the PG response in people with T2D with an ~20% improvement in glycaemic values. These findings provide case‐study evidence for plant‐based treatments in T2D to complement a healthy lifestyle and pharmacotherapy. [ABSTRACT FROM AUTHOR]

Maltreatment during childhood has many long‐lasting effects. Victims often become parents who experience parenting difficulties, therefore contributing to the intergenerational cycle of maltreatment. This paper highlights the consequences of severe trauma during childhood on two processes critical for a sensitive response, namely the recognition of and the initial reaction to emotional signals. We argue that most interventions focus on the observed parental response to children's behaviors or on parental interpretation of children's signals, that is, the attribution of meaning or intent to the signal. Interventions should better integrate research indicating that a history of childhood maltreatment could impair the capacity to correctly identify the emotion and the immediate reaction to these signals. By failing to acknowledge these long‐lasting consequences of childhood maltreatment, scholars and practitioners might never achieve true success in intervening with families in the hope of breaking the intergenerational cycle of maltreatment. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of Brugada syndrome (BrS) may be established by exposing a Type 1 Brugada pattern using a sodium channel blocker. Data on the outcomes of different patient populations with drug‐induced Type 1 Brugada pattern are limited. The present study reports on the characteristics and outcome of subjects with ajmaline induced Type 1 Brugada pattern. Methods: A multicenter retrospective study including all consecutive cases of ajmaline‐induced Type 1 Brugada pattern from seven centers. Results: A total of 260 patients (69.9% males, mean age 43.4 ± 13.5) were included. Additional characteristics included history of syncope (n = 56, 21.5%), family history of BrS (n = 58, 22.3%) or sudden cardiac death (n = 47, 18.1%) and ventricular fibrillation (n = 3, 1.2%). Patients were divided into those meeting current diagnostic criteria for drug‐induced BrS (DIBrS) and compared to the drug‐induced Brugada pattern (DIBrECG). Females were significantly overrepresented in the DIBrS group (n = 50, 40% vs. n = 29, 21.5%, p =.001). A significantly higher prevalence of type 2/3 Brugada ECG at baseline was found in the DIBrECG group (n = 108, 80.8% vs. n = 75, 60% in the DIBrS, p =.026). During a median follow up of three (IQR 1.50–5.32) years, a single event of significant arrhythmia occurred in the DIBrS group. Conclusion: Less than half of subjects with ajmaline‐induced Brugada pattern met current criteria for BrS. These individuals had very low rate of adverse outcomes during a follow up of 3 years, irrespective of the indication for the test or eligibility for the BrS diagnosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Subtle executive dysfunction is common in people newly diagnosed with Parkinson disease (PD), even when general cognitive abilities are intact. This study examined the Short Weekly Calendar Planning Activity (WCPA‐10)'s known‐group construct validity, comparing persons with PD to healthy controls (HCs) and nonmanifesting carriers of LRRK2 and GBA gene mutations to HCs. Additionally, convergent and ecological validity was examined. Methods: The study included 73 participants: 22 with idiopathic PD (iPD) who do not carry any of the founder GBA mutations or LRRK2‐G2019S, 29 nonmanifesting carriers of the G2019S‐LRRK2 (n = 14) and GBA (n = 15) mutations, and 22 HCs. Known‐group validity was determined using the WCPA‐10, convergent validity by also using the Montreal Cognitive Assessment (MoCA) and Color Trails Test (CTT), and ecological validity by using the WCPA‐10, Schwab and England Activities of Daily Living Scale (SE ADL), and Physical Activity Scale for the Elderly (PASE). Results: Known‐group validity of the WCPA‐10 was established for the iPD group only; they followed fewer rules (p = 0.020), were slower (p = 0.003) and less efficient (p = 0.001), used more strategies (p = 0.017) on the WCPA‐10, and achieved significantly lower CTT scores (p < 0.001) than the HCs. The nonmanifesting carriers and HCs were similar on all cognitive tests. Convergent and ecological validity of the WCPA‐10 were partially established, with few correlations between WCPA‐10 outcome measures and the MoCA (r = 0.50, r = 0.41), CTT‐2 (r = 0.43), SE ADL (r = 0.41), and PASE (r = 0.54, r = 0.46, r = 0.31). Conclusions: This study affirms the known‐group validity for most (four) WCPA‐10 scores and partially confirms its convergent and ecological validity for PD. [ABSTRACT FROM AUTHOR]

Background: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2‐I) in patients with left ventricular assist devices (LVAD) are unknown. Methods: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2‐I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2‐I. Results: SGLT2‐I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2‐I initiation was 108 days, IQR (26–477). Following SGLT2‐I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2–38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7–4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23–11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2‐I initiation (p > 0.2 for all). No adverse events were recorded during median follow‐up of 354 days, IQR (206–786). Conclusion: SGLT2‐I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is recognized as an imminent and growing global health threat. New antimicrobial drugs are urgently needed due to the decreasing effectiveness of conventional small‐molecule antibiotics. Antimicrobial peptides (AMPs), a class of host defense peptides, are emerging as promising candidates to address this need. The potential sequence space of amino acids is combinatorially vast, making it possible to extend the current arsenal of antimicrobial agents with a practically infinite number of new peptide‐based candidates. However, mining naturally occurring AMPs, whether directly by wet lab screening methods or aided by bioinformatics prediction tools, has its theoretical limit regarding the number of samples or genomic/transcriptomic resources researchers have access to. Further, manually designing novel synthetic AMPs requires prior field knowledge, restricting its throughput. In silico sequence generation methods are gaining interest as a high‐throughput solution to the problem. Here, we introduce AMPd‐Up, a recurrent neural network based tool for de novo AMP design, and demonstrate its utility over existing methods. Validation of candidates designed by AMPd‐Up through antimicrobial susceptibility testing revealed that 40 of the 58 generated sequences possessed antimicrobial activity against Escherichia coli and/or Staphylococcus aureus. These results illustrate that AMPd‐Up can be used to design novel synthetic AMPs with potent activities. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore the effects of a green Mediterranean (green‐MED) diet, which is high in dietary polyphenols and green plant‐based protein and low in red/processed meat, on cardiovascular disease and inflammation‐related circulating proteins and their associations with cardiometabolic risk parameters. Methods: In the 18‐month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT‐PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green‐MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green‐MED diet group also consumed green tea (3–4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat. Proteome panels were measured at three time points using Olink CVDII. Results: At baseline, a dominant protein cluster was significantly related to higher phenotypic cardiometabolic risk parameters, with the strongest associations attributed to magnetic resonance imaging‐assessed visceral adiposity (false discovery rate of 5%). Overall, after 6 months of intervention, both the MED and green‐MED diets induced improvements in cardiovascular disease and proinflammatory risk proteins (p < 0.05, vs. healthy dietary guidelines), with the green‐MED diet leading to more pronounced beneficial changes, largely driven by dominant proinflammatory proteins (IL‐1 receptor antagonist protein, IL‐16, IL‐18, thrombospondin‐2, leptin, prostasin, galectin‐9, and fibroblast growth factor 21; adjusted for age, sex, and weight loss; p < 0.05). After 18 months, proteomics cluster changes presented the strongest correlations with visceral adiposity reduction. Conclusions: Proteomics clusters may enhance our understanding of the favorable effect of a green‐MED diet that is enriched with polyphenols and low in red/processed meat on visceral adiposity and cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Background: There is a need to develop biomarkers for diagnosis and prediction of treatment responses in depression and post‐traumatic stress disorder (PTSD). Methods: Cross‐sectional study examining correlations between tear inflammatory proteins, meibum and tear sphingolipids, and symptoms of depression and PTSD‐associated anxiety. Ninety individuals filled depression (Patient Health Questionnaire 9, PHQ‐9) and PTSD‐associated anxiety (PTSD Checklist‐Military Version, PCL‐M) questionnaires. In 40 patients, a multiplex assay system was used to quantify 23 inflammatory proteins in tears. In a separate group of 50 individuals, liquid chromatography‐mass spectrometry was performed on meibum and tears to quantify 34 species of sphingolipids, encompassing ceramides, monohexosyl ceramides and sphingomyelins. Results: The mean age of the population was 59.4 ± 11.0 years; 89.0% self‐identified as male, 34.4% as White, 64.4% as Black, and 16.7% as Hispanic. The mean PHQ‐9 score was 11.1 ± 7.6, and the mean PCL‐M score was 44.3 ± 19.1. Symptoms of depression and PTSD‐associated anxiety were highly correlated (ρ =0.75, p < 0.001). Both PHQ9 and PCL‐M scores negatively correlated with multiple sphingolipid species in meibum and tears. In multivariable models, meibum Monohexosyl Ceramide 26:0 (pmol), tear Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 16:0 (mol%), and tear Ceramide 26:1 (mol%) remained associated with depression and meibum Monohexosyl Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 26:0 (pmol), tear Sphingomyelin 20:0 (mol%), and tear Sphingosine‐1‐Phosphate (mol%) remained associated with PTSD‐associated anxiety. Conclusions: Certain meibum and tear sphingolipid species were related to mental health indices. These interactions present opportunities for innovative diagnostic and therapeutic approaches for mental health disorders. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a critical public health concern, necessitating the exploration of alternative treatments. While antimicrobial peptides (AMPs) show promise, assessing their toxicity using traditional wet lab methods is both time‐consuming and costly. We introduce tAMPer, a novel multi‐modal deep learning model designed to predict peptide toxicity by integrating the underlying amino acid sequence composition and the three‐dimensional structure of peptides. tAMPer adopts a graph‐based representation for peptides, encoding ColabFold‐predicted structures, where nodes represent amino acids and edges represent spatial interactions. Structural features are extracted using graph neural networks, and recurrent neural networks capture sequential dependencies. tAMPer's performance was assessed on a publicly available protein toxicity benchmark and an AMP hemolysis data we generated. On the latter, tAMPer achieves an F1‐score of 68.7%, outperforming the second‐best method by 23.4%. On the protein benchmark, tAMPer exhibited an improvement of over 3.0% in the F1‐score compared to current state‐of‐the‐art methods. We anticipate tAMPer to accelerate AMP discovery and development by reducing the reliance on laborious toxicity screening experiments. [ABSTRACT FROM AUTHOR]

Objectives Animals Procedures Results Conclusions In equine glaucoma, topical treatment with carbonic anhydrase inhibitors (CAIs) is recommended. Oral acetazolamide, a systemic CAI, is used in horses with hyperkalemic periodic paralysis. Information regarding its effect on equine intraocular pressure (IOP) is scarce. The aim of the study was to determine the effect of oral acetazolamide treatment on IOP in horses, in a case–control study.Ten healthy horses.Horses were treated with oral acetazolamide (4.4 mg/kg) BID for 1 week. Serum acetazolamide concentrations were determined by liquid chromatography/tandem mass spectrometry, and IOP were measured before treatment, daily during treatment, and at 48 and 72 h after treatment.Acetazolamide serum levels reached steady state at 72 h after the first oral dose. In a mixed effect model logistic regression, there was a significant decrease in IOP on the third treatment day, of 2.4 mmHg (p = .012) and 2.7 mmHg (p = .006) in the left (OS) and right eye (OD), respectively. On the seventh day, there was a decrease in 2.5 mmHg (p = .008) and 2.7 mmHg (p = .007) OS and OD, respectively. A significant increase occurred 48 h following treatment discontinuation (3.6 mmHg, p < .001 and 3.5 mmHg, p < .001 OS and OD, respectively). The area under the concentration versus time curve (AUC(0–10h)) was 1.1 ± 0.5 μg/mL*h, mean residence time 6.7 ± 4.3 h, peak plasma concentration (Cmax) 0.4 ± 0.4 μg/mL and time to reach Cmax 1.8 h. There was a significant increase in serum concentrations 1, 2, 48, 72, and 156 h following the first drug administration (p < .05).Further studies are required to determine whether acetazolamide is a potential treatment for equine glaucoma. [ABSTRACT FROM AUTHOR]

Objective: This study examined the long‐term effects of the COVID‐19 pandemic on adolescents' substance use, digital media use, and symptoms of internet, gaming, and social media addiction. Method: A nationally representative longitudinal cohort of 1665 Israeli teens and preteens, aged 9–16, completed questionnaires assessing substance use prevalence, daily screen time, symptoms of media addiction, and potential risk and protective factors. Data were collected before the pandemic (October 2019), after the second wave lockdown (November 2020), and after the fifth wave (April 2022) in Israel. Results: The analysis documented significant increases in substance use, daily screen time, and social media addiction indices over time. Gratitude, life satisfaction, positive emotions, future orientation, grit, and secure attachment emerged as significant protective factors. Sensation‐seeking, negative emotions, and mental health symptoms were identified as risk factors. Conclusions: These findings highlight the importance of educational and public mental health services in addressing the pandemic's long‐term impact on the mental health and addictive behaviors of adolescents. They also emphasize the significance of enhancing protective factors and reducing risk factors to effectively mitigate substance and digital media abuse among adolescents. [ABSTRACT FROM AUTHOR]

According to coercion theory (Patterson, 1982, 2016), children's aggression is developed and maintained through transactional processes between parents and their children that unfold over time. The theory provides a model of the behavioral contingencies that explain how parents and children mutually "train" each other to behave in ways that over time increase the likelihood of children's aggression and decrease parents' control over this aggression. Although the theory characterizes the interactions that often lead to dysfunctional family processes and children's aggression, its focus on observable, interpersonal negativity has resulted in research that largely overlooks intraindividual phenomena, such as the internal experiences that drive parents' expressed negativity. In this article, I present empirical and theoretical work that supports an expanded focus of coercion theory to include emotion as an internal mechanism of reinforcement that facilitates and maintains coercive family processes and children's antisocial development. [ABSTRACT FROM AUTHOR]

The present study explores the impact of nonviolent communication (NVC) intervention on advantaged group members' actual participation in collective action on behalf of disadvantaged outgroups, also known as solidarity‐based collective action (SBCA). It also examines the mediating role of hope and empathy in this process. Using an experimental longitudinal field study in the context of the Israeli–Palestinian conflict, Jewish Israelis (N = 220) were randomly assigned either to an NVC or to a control condition. Results indicated that, relative to the control, participants in the NVC condition showed an increased tendency to engage in activities that are considered part of SBCA 6 weeks after the intervention. Furthermore, the NVC intervention affected both hope and empathy by maintaining higher levels of hope 6 weeks after intervention and by increasing empathy immediately after intervention. Yet hope, but not empathy, mediated the effect of the NVC intervention on participation in SBCA. Theoretical and applicable implications are discussed. [ABSTRACT FROM AUTHOR]

Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme‐linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody‐mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA‐ to Luminex‐based testing. For this study, bio‐banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre‐existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow‐up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex‐based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA‐ to Luminex‐based HLA testing was associated with a significant decrease in AMR occurrence post‐transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex‐based testing has the added value of preventing low‐risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated heterogeneous adaptive outcomes across the autism spectrum; however, the current literature remains limited in elucidating turning points and associated factors for longitudinal variability (chronogeneity). To address these empirical gaps, we aimed to provide a finer‐grained characterization of trajectories of adaptive functioning from early childhood to adolescence in autism. Methods: Our sample (N = 406) was drawn from an inception cohort of children diagnosed Autistic at ages 2–5. Adaptive functioning was assessed with Vineland Adaptive Behavior Scales (VABS, 2nd Edition) across 6 visits from the time of diagnosis by age 18. Parallel‐process latent growth curve modeling were used to estimate domain‐level VABS trajectories, followed by latent class growth analysis to identify trajectory subgroups. Child characteristics at diagnosis, family demographics, and participation outcomes at adolescence were compared across subgroups. Results: Piecewise latent growth models best described VABS trajectories with two turning points identified at around ages 5‐6 and 9–10, respectively reflecting transitions into school age and early adolescence. We parsed four VABS trajectory subgroups that vary by level of functioning and change rate for certain domains and periods. Around 16% of the sample exhibited overall adequate functioning (standard score >85) with notable early growth and social adaptation during adolescence. About 21% showed low adaptive functioning (standard score ≤70), with decreasing slopes by age 6 followed by improvements in communication and daily‐living skills by age 10. The other two subgroups (63% in total) were characterized by adaptive functioning between low and adequate levels, with relatively stable trajectories entering school age. These subgroups differed most in their cognitive ability at diagnosis, household income, and social participation in adolescence. Conclusions: We identified key individual and family characteristics and time windows associated with distinct adaptive functioning trajectories, which have important implications for providing timely and tailored supports to Autistic people across developmental stages. [ABSTRACT FROM AUTHOR]

Objective: Data available at admission to delivery of nulliparous has rarely been investigated for prediction of obstetric anal sphincter injury (OASI). The aim of the present study was to study risk factors for OASI in nulliparous based on information available at admission. Methods: A retrospective study of all nulliparous women undergoing labor, during March 2011 to January 2021 was performed. We compared women with OASI following delivery to those without by univariate and multivariable regression. Results: A total of 30 262 deliveries were included and 4181 (13.4%) of those were delivered by an emergent cesarean delivery. OASI followed 453 (1.5%) deliveries. Women in the OASI group were younger 29 ± 4.4 versus 30 ± 4.8, P = 0.001. In a multivariable regression analysis, higher sonographic estimated fetal weight was positively associated with OASI occurrence (aOR, 95% CI: 1.13 [1.00–1.29]). Maternal age was inversely associated with OASI occurrence (adjusted odds ratio [aOR], 95% confidence interval [CI] 0.95 [0.92–0.97]). Conclusion: Sonographic fetal weight estimation is an independent risk factor for OASI occurrence that may be available at admission for delivery among nulliparous women. Synopsis: Younger maternal age and higher sonographic fetal weight estimation are risk factors for obstetric anal sphincter occurrence that can be available at admission for. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic underscored the crucial importance of enhanced indoor air quality control measures to mitigate the spread of respiratory pathogens. Far‐UVC is a type of germicidal ultraviolet technology, with wavelengths between 200 and 235 nm, that has emerged as a highly promising approach for indoor air disinfection. Due to its enhanced safety compared to conventional 254 nm upper‐room germicidal systems, far‐UVC allows for whole‐room direct exposure of occupied spaces, potentially offering greater efficacy, since the total room air is constantly treated. While current evidence supports using far‐UVC systems within existing guidelines, understanding the upper safety limit is critical to maximizing its effectiveness, particularly for the acute phase of a pandemic or epidemic when greater protection may be needed. This review article summarizes the substantial present knowledge on far‐UVC safety regarding skin and eye exposure and highlights research priorities to discern the maximum exposure levels that avoid adverse effects. We advocate for comprehensive safety studies that explore potential mechanisms of harm, generate action spectra for crucial biological effects and conduct high‐dose, long‐term exposure trials. Such rigorous scientific investigation will be key to determining safe and effective levels for far‐UVC deployment in indoor environments, contributing significantly to future pandemic preparedness and response. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of the changes in treatment patterns before, during and after the COVID‐19 pandemic on best‐corrected visual acuity (BCVA) in previously treated neovascular age‐related macular degeneration (nAMD) patients. Methods: A multi‐centre, retrospective, observational study of consecutive nAMD patients during 2019–2021. Data collected included demographics, BCVA, dates of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) injections and clinic visits. Results: A total of 1652 eyes of 1652 nAMD patients were included, out of which 850 eyes were assessed in 2019 (pre‐COVID‐19), 630 eyes were assessed in 2020 (COVID‐19) and 974 eyes were assessed in 2021 (post‐COVID‐19). During the COVID‐19 period, the mean number of anti‐VEGF injections was significantly lower than the corresponding pre‐COVID‐19 and post‐COVID‐19 periods (5.55 compared to 6.13 and 6.60, respectively p < 0.01). A constant lower ratio of injections per patient/month was observed during COVID‐19 compared to previous and following years, with a notable decline during March–April, reaching a ratio of 0.4 in 2020 versus 0.65 in 2019 and 0.62 in 2021 (p < 0.01). Baseline BCVA (0.825, p < 0.001), number of injections (−0.007, p < 0.001), gender (−0.027, p = 0.037) and age (0.004, p < 0.001) were shown to be significant predictors of final BCVA. Conclusion: During the COVID‐19 period, patients were treated with significantly less intravitreal anti‐VEGF injection compared to the previous year with compensation in the following year. These changes in treatment patterns did not have a significant impact on BCVA outcomes. Age, gender, baseline BCVA and number of injections are predictors of final visual outcomes. [ABSTRACT FROM AUTHOR]

Prolonging the lifespan of transplanted organs is critical to combat the shortage of this life‐saving resource. Chronic rejection, with irreversible demise of the allograft, is often caused by the development of donor‐specific HLA antibodies. Currently, enumerating molecular (amino acid) mismatches between recipient and donor is promoted to identify patients at higher risk of developing HLA antibodies, for use in organ allocation, and immunosuppression‐minimization strategies. We have counseled against the incorporation of such approaches into clinical use and hypothesized that not all molecular mismatches equally contribute to generation of donor‐specific immune responses. Herein, we document statistical shortcomings in previous study design: for example, use of individuals who lack the ability to generate donor‐specific‐antibodies (HLA identical) as part of the negative cohort. We provide experimental evidence, using CRISPR‐Cas9‐edited cells, to rebut the claim that the HLAMatchmaker eplets represent "functional epitopes." We further used unique sub‐cohorts of patients, those receiving an allograft with two HLA‐DQ mismatches yet developing antibodies only to one mismatch (2MM1DSA), to interrogate differential immunogenicity. Our results demonstrate that mismatches of DQα05‐heterodimers exhibit the highest immunogenicity. Additionally, we demonstrate that the DQα chain critically contributes to the overall qualities of DQ molecules. Lastly, our data proposes that an augmented risk to develop donor‐specific HLA‐DQ antibodies is dependent on qualitative (evolutionary and functional) divergence between recipient and donor, rather than the mere number of molecular mismatches. Overall, we propose an immunological mechanistic rationale to explain differential HLA‐DQ immunogenicity, with potential ramifications for other pathological processes such as autoimmunity and infections. [ABSTRACT FROM AUTHOR]

Huntington’s disease (HD) is an incurable inherited disorder caused by a repeated expansion of glutamines in the huntingtin gene (Htt). The mutant protein causes neuronal degeneration leading to severe motor and psychological symptoms. Selective downregulation of the mutant Htt gene expression is considered the most promising therapeutic approach for HD. We report the identification of small molecule inhibitors of Spt5-Pol II, SPI-24 and SPI-77, which selectively lower mutant Htt mRNA and protein levels in HD cells. In the BACHD mouse model, their direct delivery to the striatum diminished mutant Htt levels, ameliorated mitochondrial dysfunction, restored BDNF expression, and improved motor and anxiety-like phenotypes. Pharmacokinetic studies revealed that these SPIs pass the blood-brain-barrier. Prolonged subcutaneous injection or oral administration to early-stage mice significantly delayed disease deterioration. SPI-24 long-term treatment had no side effects or global changes in gene expression. Thus, lowering mutant Htt levels by small molecules can be an effective therapeutic strategy for HD. [ABSTRACT FROM AUTHOR]

Introduction. Falls among hospitalized patients continue to pose a serious threat to patient safety worldwide. Effective fall-prevention education is considered vital for fall prevention. Nurses' resilience and proactivity may improve the fall-prevention education nurses provide to patients, but how to motivate nurses' proactivity remains unsolved. This study aimed to examine whether (1) nurse's resilience and social capital are jointly associated with nurse proactivity and (2) adherence to procedures further moderates the relationships between nurse proactivity and the fall prevention education provided to patients by the nurse. Methods. A nested (∼3 patients per nurse) cross-sectional observational design has been employed in this study. 101 bedside registered nurses were recruited from fourteen internal and surgical wards at a medium-size hospital. For each nurse, ∼3 of their newly admitted patients were recruited (total of 271 patients). Nurses completed validated questionnaires on personal resilience, social capital, following procedures, and sociodemographic data. Fall-prevention education was assessed via a short-structured interview with patients. Hypotheses were analyzed using the Hayes PROCESS macro. Results. Social capital, nurse resilience, and their interaction were associated with proactive behavior. Proactive behavior, adherence to procedures, and their interaction (β = −0.57, p < 0.01) were associated with patient education for fall prevention given by nurses. The moderated-mediation model was significant under medium and high levels of social capital and low levels of adherence to procedures. Conclusion. The study highlights the importance of nurse proactivity in educating patients about fall prevention, especially when adherence to procedures in the ward is perceived as low. Furthermore, nurses' proactivity can be promoted by nurturing both their resilience and their social capital. Nursing managers should nurture proactivity at the work environment of the 21-century, by fostering resilience and enculturing social capital. Concomitantly, employees should be educated at ways to promote personal resilience and engage in wise proactivity. [ABSTRACT FROM AUTHOR]

Background: Patients with severe B‐cell depletion related to hematological malignancies or B‐cell targeted therapy suffer from impaired antibody responses to SARS‐CoV‐2 and are at risk for prolonged COVID‐19. In this population, COVID‐19 convalescent plasma (CCP) may provide passive immunity, enhance immune response, and promote virus neutralization. This study evaluated outcomes of B‐cell depleted patients with persistent COVID‐19 treated with CCP. Study Design and Methods: This analysis included all consecutive severely B‐cell depleted patients with persistent COVID‐19, receiving CCP at Rambam between 01.2022–02.2023. Persistent COVID‐19 was defined as the presence of symptoms for ≥14 days in patients with negative SARS‐CoV‐2 nucleocapsid antibody test results. Results: Twenty patients met inclusion criteria, 17 of whom had hematological malignancies, two suffered from rheumatoid arthritis and one had both. Twelve patients received anti‐CD‐20 treatment, one ‐ CAR‐T cells and three underwent stem cell transplantation. The median duration of COVID‐19 symptoms was 27.5 days (range 14–97); 12 patients had mild‐to‐moderate COVID‐19 and 8 had severe infection. Sixteen patients required hospitalization. The majority of patients received other COVID‐19 therapies before CCP. Within a median of two days (range 1–16) post‐infusion, 19/20 patients clinically improved. No CCP‐associated adverse events were documented. COVID‐19 symptoms recurred in 3 of the improved patients. Two patients died from COVID‐19 on days 1 and 90 following the first CCP infusion. Discussion: In severely B‐cell depleted patients with persistent COVID‐19, CCP is safe and associated with rapid clinical improvement. This subset of immunocompromised patients could particularly benefit from CCP administration. [ABSTRACT FROM AUTHOR]

Graft‐versus‐host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments. [ABSTRACT FROM AUTHOR]

Aim: To quantify the future risk of type 2 diabetes (T2D) in women with gestational diabetes (GD) based on baseline metabolic characteristics and the number of abnormal values during a 3‐hour 100‐g oral glucose tolerance test (OGTT). Materials and Methods: We conducted a population‐based retrospective cohort study of 10 023 pregnant women who underwent testing for GD in a large health maintenance organization in Israel using a 100‐g OGTT. Glucose values were obtained at four time points, 0, 60, 120 and 180 minutes. Results: We identified 9939 women who met the study criteria. Median follow‐up was 3.25 (interquartile range 1.5‐5.1; maximum 10.1) years. Using women without GD as reference, women with GD were at an increased risk of future T2D (hazard ratio [HR] 5.33 [95% confidence interval {CI} 3.86‐7.34]). This risk increased with a greater number of abnormal OGTT values, with the highest risk seen in women with four abnormal values (HR 16.67 [95% CI 7.94‐35.01]). In a multivariate model, a higher number of abnormal values, Arab ethnicity, higher body mass index, triglycerides and prepregnancy glucose were significantly associated with increased risk. Future T2D risk was also affected by the type of OGTT abnormality; an abnormal fasting value had the greatest risk, whereas an abnormal 3‐hour value had the lowest risk (HR 3.61 [95% CI 2.42‐5.38] vs. 1.50 [95% CI 0.93‐2.43], respectively). Conclusions: GD is a heterogenous disease, with varying degrees of glucose intolerance and subsequent T2D risk. Targeting interventions to women at the highest risk may help to improve postpartum adherence and effective long‐term follow‐up strategies. [ABSTRACT FROM AUTHOR]

This article discusses a case of cytomegalovirus (CMV) colitis in a 47-year-old female patient who was undergoing chimeric antigen receptor-T cell (CAR-T) therapy for double-hit large B-cell lymphoma. The patient developed lower gastrointestinal bleeding and was found to have active arterial bleeding in the right colon. Colonoscopy revealed ulcers and a visible vessel with active bleeding, and pathology confirmed the presence of CMV. The patient was treated with ganciclovir and showed a good clinical response. The article emphasizes the importance of screening for CMV reactivation in CAR-T patients and promptly initiating antiviral therapy for a favorable outcome. [Extracted from the article]

Obesity is associated with negative effects on the brain. We exploit Artificial Intelligence (AI) tools to explore whether differences in clinical measurements following lifestyle interventions in overweight population could be reflected in brain morphology. In the DIRECT‐PLUS clinical trial, participants with criterion for metabolic syndrome underwent an 18‐month lifestyle intervention. Structural brain MRIs were acquired before and after the intervention. We utilized an ensemble learning framework to predict Body‐Mass Index (BMI) scores, which correspond to adiposity‐related clinical measurements from brain MRIs. We revealed that patient‐specific reduction in BMI predictions was associated with actual weight loss and was significantly higher in active diet groups compared to a control group. Moreover, explainable AI (XAI) maps highlighted brain regions contributing to BMI predictions that were distinct from regions associated with age prediction. Our DIRECT‐PLUS analysis results imply that predicted BMI and its reduction are unique neural biomarkers for obesity‐related brain modifications and weight loss. [ABSTRACT FROM AUTHOR]

The E. coli transcriptome at the cell's poles (polar transcriptome) is unique compared to the membrane and cytosol. Several factors have been suggested to mediate mRNA localization to the membrane, but the mechanism underlying polar localization of mRNAs remains unknown. Here, we combined a candidate system approach with proteomics to identify factors that mediate mRNAs localization to the cell poles. We identified the pole-to-pole oscillating protein MinD as an essential factor regulating polar mRNA localization, although it is not able to bind RNA directly. We demonstrate that RNase E, previously shown to interact with MinD, is required for proper localization of polar mRNAs. Using in silico modeling followed by experimental validation, the membrane-binding site in RNase E was found to mediate binding to MinD. Intriguingly, not only does MinD affect RNase E interaction with the membrane, but it also affects its mode of action and dynamics. Polar accumulation of RNase E in ΔminCDE cells resulted in destabilization and depletion of mRNAs from poles. Finally, we show that mislocalization of polar mRNAs may prevent polar localization of their protein products. Taken together, our findings show that the interplay between MinD and RNase E determines the composition of the polar transcriptome, thus assigning previously unknown roles for both proteins. Synopsis: A subset of E. coli transcripts localizes to the cell poles via an unknown mechanism. Here, the interaction of MinD and RNase E is shown to prevent site-specific degradation of polar mRNAs, thus favoring their enrichment in the cell poles. Candidate approach and proteomic analysis identify MinD and RNase E as regulators of polar mRNA localization. MinD interacts with a short peptide within the membrane-targeting sequence of RNase E. In the absence of MinD, RNase E transiently accumulates at cell poles. Polar accumulation of RNase E in ΔminCDE cells destabilizes polar mRNAs, resulting in their elimination from the poles and potentially affecting localization of the encoded proteins. The polar transcriptome of E. coli is regulated by MinD-dependent inhibition of RNase E recruitment to the cell pole. [ABSTRACT FROM AUTHOR]