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Abstract Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We performed comprehensive molecular, immune, microbiome, and metabolic profiling on samples of trial patients. Here, we show increased T and B cell clusters and distinct microbial patterns with amino acid and lipid metabolism are linked to exceptional clinical responses. This study suggests the immune milieu and host-microbiome can be leveraged to improve antitumor response in future immunotherapy trials.

This study aimed to develop a compensatory growth model using growing beef cattle by changing dietary protein and to investigate the underlying mechanisms of compensatory protein deposition in muscle tissue. Twelve Charolais bulls were randomly assigned to one of two groups with two periods: 1) a control group (CON) fed a 13% crude protein (CP) diet for 6 weeks; 2) a treatment group (REC) fed a 7% CP diet for 4 weeks (restriction period) and fed a 13% CP diet in the following 2 weeks (re-alimentation period). Growth performance, digestibility, nitrogen balance, targeted metabolomics of amino acids (AA) in plasma, and transcriptional profiling in muscle tissue were analyzed. Protein restriction decreased average daily gain (ADG; P

Abstract Tidal marshes are threatened coastal ecosystems known for their capacity to store large amounts of carbon in their water-logged soils. Accurate quantification and mapping of global tidal marshes soil organic carbon (SOC) stocks is of considerable value to conservation efforts. Here, we used training data from 3710 unique locations, landscape-level environmental drivers and a global tidal marsh extent map to produce a global, spatially explicit map of SOC storage in tidal marshes at 30 m resolution. Here we show the total global SOC stock to 1 m to be 1.44 Pg C, with a third of this value stored in the United States of America. On average, SOC in tidal marshes’ 0–30 and 30–100 cm soil layers are estimated at 83.1 Mg C ha−1 (average predicted error 44.8 Mg C ha−1) and 185.3 Mg C ha−1 (average predicted error 105.7 Mg C ha−1), respectively.

Abstract Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex genetic alterations. The basic-helix-loop-helix (bHLH) transcription factors ASCL1 and OLIG2 are dynamically co-expressed in GBMs; however, their combinatorial roles in regulating the plasticity and heterogeneity of GBM cells are unclear. Here, we show that induction of somatic mutations in subventricular zone (SVZ) progenitor cells leads to the dysregulation of ASCL1 and OLIG2, which then function redundantly and are required for brain tumor formation in a mouse model of GBM. Subsequently, the binding of ASCL1 and OLIG2 to each other’s loci and to downstream target genes then determines the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in specifying highly migratory neural stem cell (NSC)/astrocyte-like tumor cell types, which are marked by upregulation of ribosomal protein, oxidative phosphorylation, cancer metastasis, and therapeutic resistance genes.

Abstract The most recent searches by the ATLAS and CMS Collaborations in final states with soft leptons and missing transverse energy show mild excesses predominantly associated with dilepton invariant masses of about $$10{-}20$$ 10 - 20 GeV, which can result from decays of electroweakinos that are heavier than the lightest neutralino by $$\mathcal {O}(10)$$ O ( 10 ) GeV. On the other hand, these analyses are insensitive to electroweakino mass splittings smaller than about 5 GeV. In previous work, we demonstrated that while recent searches in the monojet channel can exclude some of the smallest $$\mathcal {O}(1)$$ O ( 1 ) GeV mass splitting configurations for electroweakinos, they also exhibit excesses that can overlap with the soft-lepton excesses in certain models, including a simplified scenario with pure higgsinos. In this work we dive deeper into these excesses, studying the analyses in detail and exploring an array of models that go beyond the simplified scenarios considered by the experimental collaborations. We show that, in the Minimal Supersymmetric Standard Model, the overlapping excesses are not unique to the pure-higgsino limit, instead persisting in realistic parameter space featuring a bino-like lightest supersymmetric particle with some wino admixture. On the other hand, for the Next-to-Minimal Supersymmetric Standard Model with a singlino-like lightest supersymmetric particle and higgsino-like next-to-lightest supersymmetric particle(s), the excess in the two-lepton channel fits rather well with the parameter space predicting the correct relic abundance through freeze out, but the monojet fit is much poorer. Interestingly, the excesses either do not overlap or do not exist at all for two non-supersymmetric models seemingly capable of producing the correct final states.

Abstract The present study examined the psychometric properties of the Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS). A total of 742 Italian participants (84.6% female), with a mean age of 33.08 years (SD = 12.44) took part in a cross-sectional survey study. Confirmatory factor analysis and Rasch analysis were used to examine the psychometric properties. The CFA showed that the SWEMWBS had a unidimensional structure with robust psychometric properties and showed good internal consistencies (Cronbach’s alpha 0.88; McDonald’s omega 0.91). Overall, most items showed no substantial differential item functioning in the Rasch analysis, except for Item 7, indicating that female participants reported more difficulty with this item than the male participants. The SWEMWBS was positively associated with life satisfaction and negativity associated with general psychological distress (i.e., anxiety, stress, and depression). In sum, the SWEMWBS showed robust psychometric properties capable of assessing positive aspects of mental health and well-being among Italian-speaking adults.

Abstract While racial inequities in dementia risk are well-documented in the United States, research has paid less attention to role of US Southern context in shaping dementia risk through life course exposures. In this study, we examine how Southern birth and Southern residence in adulthood are linked to dementia incidence for Black and White older adults in the United States. Using the Health and Retirement Study (N = 15,613), we estimate a series of hazard models to evaluate how life course risk factors such as childhood health and social disadvantage, education, adult socioeconomic status, health behaviors, and cardiometabolic conditions impact the association between Southern life course residency and dementia risk. We find different patterns in how Southern life course context shapes dementia risk among Black and White adults, with dementia risk among Blacks especially sensitive to combinations of Southern life course context. These findings demonstrate the importance of considering potential heterogenous life course pathways to cognitive aging and health that may be shaped by larger socio-historical experiences.

Abstract Background Hypertension is the most common cardiovascular disease in Peru despite the availability of cost-effective, evidence-based treatment. Here we describe the rationale and study design for a hybrid type 2 randomized controlled trial to test the implementation and effectiveness of a community health worker (CHW)-led hypertension control program within the national primary care system in Puno, Peru. Methods We will recruit 1068 adult participants with hypertension aged ≥ 18 years in Puno, Peru, via facility-based enrollment and community health fairs. Participants will be individually randomized (1:1) to either continue with usual care or participate in a 12-month CHW-led home-based hypertension control program consisting of blood pressure monitoring, medication adherence support, and healthy lifestyle counseling. Outcome development and reporting are guided by the Consolidated Framework for Implementation Research (CFIR), the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, and the Proctor et al. framework. Clinical effectiveness outcomes include mean change in systolic blood pressure (primary outcome), diastolic blood pressure, and HbA1C. Implementation outcomes include fidelity (i.e., CHW protocol adherence and dose), reach, adoption, sustainability, acceptability, and cost-effectiveness. Discussion The ANDES trial is testing the first CHW-led multicomponent strategy for hypertension and type 2 diabetes management in Peru. This type 2 hybrid trial will provide critical insights into the individual, community, and system-level factors necessary for successful implementation and effectiveness. These data can inform the future adaptation and scaling of the ANDES strategy in Peru and other LMICs, as well as influence policies at the system level to support this transition. Furthermore, by addressing both hypertension and diabetes, the ANDES strategy supports integrated care approaches advocated by the WHO HEARTS technical package, ultimately enhancing health outcomes and reducing morbidity and mortality in the region. Trial registration ClinicalTrials.gov, ID: NCT05524987 , Addressing Hypertension and Diabetes through Community-Engaged Systems in Puno, Peru (ANDES study), prospectively registered on September 1, 2021.

Abstract Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomic resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomic resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, anti-predator strategies, and resilience and adaptive responses. They also serve as essential models for studying broad genomic traits, such as evolutionary genome expansions and contractions, as they exhibit the widest range of genome sizes among all animal taxa and possess multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The emergence of long-read sequencing technologies, combined with advanced molecular and computational techniques that improve scaffolding and reduce computational workloads, is now making it possible to address some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC, https://mvs.unimelb.edu.au/amphibian-genomics-consortium ) in early 2023. This burgeoning community already has more than 282 members from 41 countries. The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and call on the research and conservation communities to unite as part of the AGC to enable amphibian genomics research to “leap” to the next level.

Abstract Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5’ untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS.

Abstract Objectives The study of comprehensive satisfaction with healthcare is still limited due to nonstandard measurement tools of patient satisfaction for the Chinese population. Therefore, the present study aimed to verify the validity, reliability, and measurement invariance of the revised Patient Satisfaction Questionnaire (PSQ-R) and conducted network analysis among a sample of the Chinese population. Methods A cross-sectional study using telephone surveys was conducted from April 2022 to August 2022. A total of 1377 participants who had been hospitalized completed the survey (481 males [34.9%], mean age = 49.4 years [SD ± 19.0]). Results Four factors (‘satisfaction with medical staff’, ‘satisfaction with hospital’, ‘satisfaction with medical costs’, and ‘satisfaction with medical insurance premiums’), were verified through confirmatory factor analysis (CFA) and had good equivalence across genders. The ‘satisfaction with medical staff’ and ‘satisfaction with hospital’ factors had the strongest edge intensity in the factor-level network. Conclusions The 18-item (four-factor) PSQ-R has good validity, reliability, and measurement invariance. The four dimensions appear to describe patient satisfaction well among the Chinese population who had been hospitalized. To effectively enhance patient satisfaction, the quality of healthcare service and medical staff skills should both be improved, medical insurance premiums should be increased, and medical costs should be decreased.

Objective: After Fontan palliation, patients with single-ventricle physiology are committed to chronic circulatory inefficiency for the duration of their lives. This is due in large part to the lack of a subpulmonary ventricle. A low-pressure rise cavopulmonary assist device can address the subpulmonary deficit and offset the Fontan paradox. We investigated the feasibility of a Fontan pump that is self-powered by tapping reserve pressure energy in the systemic arterial circulation. Methods: A double-inlet, double-outlet rotary pump was designed to augment Fontan flow through the total cavopulmonary connection. Pump power is supplied by a systemic arterial shunt and radial turbine, with a closed-loop shunt return to the common atrium (QP:QS 1:1). Computational fluid dynamic analysis and lumped parameter modeling of pump impact on the Fontan circulation was performed. Results: Findings indicate that a pump that can augment all 4 limbs of total cavopulmonary connection flow (superior vena cava/inferior vena cava inflow; left pulmonary artery/right pulmonary artery outflow) using a systemic arterial shunt powered turbine at a predicted cavopulmonary pressure rise of +2.5 mm Hg. Systemic shunt flow is 1.43 lumped parameter model, 22% cardiac output. Systemic venous pressure is reduced by 1.4 mm Hg with improved ventricular preload and cardiac output. Conclusions: It may be possible to tap reserve pressure energy in the systemic circulation to improve Fontan circulatory efficiency. Further studies are warranted to optimize, fabricate, and test pump designs for hydraulic performance and hemocompatibility. Potential benefits of an autonomous Fontan pump include durable physiologic shift toward biventricular health, freedom from external power, autoregulating function and exercise responsiveness, and improved quality and duration of life.

Abstract Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.

Abstract Background Previous studies have shown that the Gaming Disorder Test (GDT) and Gaming Disorder Scale for Adolescents (GADIS-A) have promising validity and reliability when assessing symptoms of gaming disorder among young adults. However, validity and reliability properties of the two scales have not been established among a Vietnamese population. Objective The present study translated the GDT and GADIS-A into Vietnamese and examined their factor structures, measurement invariance, convergent validity, concurrent validity, and divergent validity among university students. Methods A total of 610 young adults (mean age = 21.09 years; 63.4% females) were recruited using convenience sampling and who completed a paper-and-pencil survey between April and June 2023. All participants completed a demographic questionnaire, GDT, GADIS-A, and six standardized scales related to gaming disorder, social media addiction, smartphone addiction, and psychological distress. Confirmatory factor analysis (CFA), internal consistency testing, and Pearson’s correlations were performed. Results CFA showed that the GDT had a one-factor structure and the GADIS-A had a two-factor structure. The internal consistency was excellent for both scales among this population. Moreover, both GDT and GADIS-A showed convergent, concurrent, and divergent validity with other standardized scales. Conclusion The Vietnamese versions of the GDT and GADIS-A have good psychometrics, which may be utilized in future research regarding gaming disorder among Vietnamese populations.

Abstract The Malagasy stream-breeding treefrog species Boophis marojezensis contains bioacoustically and genetically highly divergent populations. Some of these populations have been defined as candidate species and emit somewhat bizarre advertisement calls consisting of multiple whistle-notes. We here enable a long-overdue taxonomic revision of this species complex by applying a museomics approach to sequence DNA from the holotype of B. marojezensis. Based on an integrative approach that combines divergence levels in mitochondrial DNA and in three nuclear-encoded genes, morphological data, and bioacoustic comparisons, we conclude that eight different species exist in this complex, seven of which are formally described herein as new. Although morphological differences between species are small and mainly separate small-sized from larger-sized species, conclusive evidence for the new species comes from their sympatric and sometimes syntopic occurrence without haplotype sharing in three nuclear genes and under maintenance of bioacoustic differences. Uncorrected genetic divergences in the mitochondrial 16S rRNA gene are >3% in almost all cases, and in some cases up to 8%. In reference to the otherworldly sounds by which these frogs fill Malagasy rainforests, some of them reminiscent of sounds of technical equipment in the fictional “Star Trek” universe, we here name and describe the seven new species in honor of fictional captains of starships, namely B. kirki sp. nov., B. picardi sp. nov., B. siskoi sp. nov., B. janewayae sp. nov., B. archeri sp. nov., B. pikei sp. nov., and B. burnhamae sp. nov. The majority of these species occur in northern Madagascar, where up to three species can occur in immediate geographical proximity, e.g., B. marojezensis, B. burnhamae sp. nov. and B. pikei sp. nov. at different elevations in the Marojejy Massif. South of 16°S latitude, only B. janewayae sp. nov., B. picardi sp. nov., and B. kirki sp. nov. are found, with the latter extending southwards to Ranomafana National Park. Our study confirms the existence of numerous morphologically cryptic and microendemic species among Madagascar’s amphibians, some of which are known only from unprotected sites and require adequate conservation management.

Abstract Background One of the most significant events in recent Afghan history is the rise of the Taliban and the war that followed, which had profound impacts on the lives of Afghans. The present study examined the mental health of Afghans living under the Taliban government. Methods Between June 5, 2023 and February 12, 2024, a cross-sectional study was conducted among the Afghan population in three key regions of Afghanistan. Data were collected using a pre-tested structured questionnaire. The 21-item Depression, Anxiety and Stress scale (DASS-21) was utilized to assess depression, anxiety and stress of the Afghan population. Ethical permission for this study was granted by the Afghanistan Center for Epidemiological Studies (ACES). Logistic regression models were employed to explore the relationship between socio-demographic characteristics and depression, anxiety, and stress among 2,698 participants. Results The prevalence of depression was 72.05%, anxiety was 71.94%, and stress was 66.49%. Multiple regression analysis indicated that gender (being female), economic status (being poor), residency (living in rural areas), education level (being illiterate), being a cigarette smoker, and having experienced a bad event during the past month were significantly associated with depression, anxiety and stress. Conclusion The findings of the present study show very high levels of anxiety, depression, and stress, most likely reflecting the profound impact of recent political, social, and economic changes. Notably, a significant majority of participants, particularly females and individuals above 35 years of age, reported severe to extremely severe mental health symptoms. The mental health crisis in Afghanistan is a complex and urgent issue that requires a comprehensive and compassionate response.

Abstract Background In line with the WHO Global Action Plan’s objective to achieve a 30% relative reduction in the mean population intake of sodium by 2025, the Nigeria Sodium Study (NaSS) team, which aimed to evaluate the implementation and scale-up of national sodium reduction programme, hosted a policy meeting May 22, 2023, in Abuja, the Federal Capital Territory of Nigeria. The aim was to deliberate on strategies for translating data on salt levels in food and dietary patterns, intending to strengthen sodium policies in Nigeria, with the ultimate goal of producing evidence-based information that can effectively guide strategies and policies for sodium reduction. Methods Policymakers from federal, state, and local government levels attended, as well as representatives from national and international universities and non-governmental organizations. Topics presented and discussed included retail survey data from the NaSS to inform front-of-package labeling, salt targets for packaged food, and best practices for supporting stakeholders in implementing best-practice evidence-informed policymaking. Results The meeting brought together 72 participants from 38 organizations, including government ministries and agencies (n = 21), international and non-governmental organizations (n = 6), and international health organizations and institutes (n = 2). Participants took decisive policy actions, including stringent national-level food system monitoring by relevant government agencies, implementing front-of-package labeling for healthier choices, establishing mandatory sodium limits for both packaged and unpackaged foods and school meals, launching diverse sector-wide educational campaigns to reduce salt use, conducting mass mobilization campaigns for awareness, and advocating for salt reduction in fast food outlets. Salt substitutes were also recognized as integral to the comprehensive sodium reduction approach. Conclusion To advance policy action, stakeholders should prioritize establishing robust monitoring systems, engage in public awareness campaigns, and collaborate with international organizations for insights. Exploring partnerships, addressing funding challenges, and implementing innovative strategies like low-sodium substitutes are crucial steps toward effective sodium reduction policies in Nigeria.

Abstract The muskox (Ovibos moschatus), an integral component and iconic symbol of arctic biocultural diversity, is under threat by rapid environmental disruptions from climate change. We report a chromosomal-level haploid genome assembly of a muskox from Banks Island in the Canadian Arctic Archipelago. The assembly has a contig N50 of 44.7 Mbp, a scaffold N50 of 112.3 Mbp, a complete representation (100%) of the BUSCO v5.2.2 set of 9225 mammalian marker genes and is anchored to the 24 chromosomes of the muskox. Tabulation of heterozygous single nucleotide variants in our specimen revealed a very low level of genetic diversity, which is consistent with recent reports of the muskox having the lowest genome-wide heterozygosity among the ungulates. While muskox populations are currently showing no overt signs of inbreeding depression, environmental disruptions are expected to strain the genomic resilience of the species. One notable impact of rapid climate change in the Arctic is the spread of emerging infectious and parasitic diseases in the muskox, as exemplified by the range expansion of muskox lungworms, and the recent fatal outbreaks of Erysipelothrix rhusiopathiae, a pathogen normally associated with domestic swine and poultry. As a genomics resource for conservation management of the muskox against existing and emerging disease modalities, we annotated the genes of the major histocompatibility complex on chromosome 2 and performed an initial assessment of the genetic diversity of this complex. This resource is further supported by the annotation of the principal genes of the innate immunity system, genes that are rapidly evolving and under positive selection in the muskox, genes associated with environmental adaptations, and the genes associated with socioeconomic benefits for Arctic communities such as wool (qiviut) attributes. These annotations will benefit muskox management and conservation.

Abstract Background Perceived weight stigma (PWS) and internalized weight stigma (IWS) are both associated with psychological distress and food addiction (FA). Using the previously proposed ‘cyclic obesity/weight-based stigma’ (COBWEBS) model, the present study extended the framework to investigate the mediating effects of IWS and psychological distress in the association between PWS and FA among young adults. Given that individuals who are overweight/have obesity have different vulnerabilities, this population was separately analyzed alongside the total study population. Methods An online survey comprising the Perceived Weight Stigma Scale, Weight Bias Internalization Scale (WBIS), Depression, Anxiety and Stress Scale-21 (DASS-21), and modified Yale Food Addiction Scale Version 2 was completed by 601 participants (59.6% females; mean age 29.3 years [SD = 6.07]). A total of 219 participants were categorized as being overweight/having obesity. Results A direct correlation was found between PWS and FA (standardized coefficient [β] = 0.28, p

The field of cardio-oncology is an expanding frontier within cardiovascular medicine, and the need for evidence-based guidelines is apparent. One of the emerging focuses within cardio-oncology is the concomitant use of medications for cardioprotection in the setting of chemotherapy regimens that have known cardiovascular toxicity. While clinical trials focusing on cardioprotection during chemotherapy are sparse, an inaugural trial exploring the prophylactic potential of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) for anthracycline (ANT)-induced cardiotoxicity has recently commenced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, though less studied in this oncology demographic, have exhibited promise in preclinical studies for conferring cardiac protection during non-ischemic toxic insults. While primarily used to reduce low-density lipoprotein, PCSK9 inhibitors exhibit pleiotropic effects, including the attenuation of inflammation, reactive oxygen species, and endothelial dysfunction. In ANT-induced cardiotoxicity, these same processes are accelerated, resulting in premature termination of treatment, chronic cardiovascular sequelae, heart failure, and/or death. This review serves a dual purpose: firstly, to provide a concise overview of the mechanisms implicated in ANT-induced cardiotoxicity, and, finally, to summarize the existing preclinical data supporting the theoretical possibility of the cardioprotective effects of PCSK9 inhibition in ANT-induced cardiotoxicity.

Abstract Background Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS. Methods We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants. Results Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric. Limitations. The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries. Conclusions We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits.

Abstract Background Hip fracture surgery under general or spinal anesthesia is a common procedure for older adults in the United States (US). Although spinal or general anesthesia can be appropriate for many patients, and the choice between anesthesia types is preference-sensitive, shared decision-making is not consistently used by anesthesiologists counseling patients on anesthesia for this procedure. We designed an Option Grid™-style conversation aid, My Anesthesia Choice─Hip Fracture, to promote shared decision making in this interaction. This study will refine the aid and evaluate its implementation and effectiveness in clinical practice. Methods The study will be conducted over 2 phases: qualitative interviews with relevant clinicians and patients to refine the aid, followed by a stepped wedge cluster randomized trial of the intervention at 6 settings in the US. Primary outcomes will include the percentage of eligible patients who receive the intervention (intervention reach) and the change in quality of patient/clinician communication (intervention effectiveness). Secondary outcomes addressing other RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) domains will also be collected. Outcomes will be compared between baseline data and an active implementation period and then compared between the active implementation period and a sustainment period. Implementation strategies are guided by three constructs from the Practical, Robust Implementation and Sustainability Model (PRISM): intervention, recipients, and implementation and sustainability infrastructure. Discussion This is a novel, large-scale trial evaluating and implementing a shared decision-making conversation aid for anesthesia choices. Strong buy-in from site leads and expert advisors will support both the success of implementation and the future dissemination of results and the intervention. Results from this study will inform the broader implementation of this aid for patients with hip fractures and can lead to the development and implementation of similar conversation aids for other anesthesia choices. Trial registration ClinicalTrials.gov, NCT06438640

Abstract Background Given that social media use (SMU) is an increasingly widespread activity among university students, more information is needed to evaluate its relationship with students’ mental health, particularly medical students. Objective The present study assessed the relationships between SMU and coping style with psychological distress and academic performance of medical students. Methods An offline cross-sectional survey conducted with 398 undergraduate medical students. The survey collected data on demographics, psychological distress (DASS-21), coping strategies (Brief COPE Scale), academic performance (grade point average) and estimated average time spent on social media per day. Structural equation modeling was used to clarify relationships between the main study variables. The study also examined the mediating effect of maladaptive coping between SMU and psychological distress. Results Students with higher levels of psychological distress were more likely to be engaged in frequent social media use. Spending more than two hours a day on social media use had a positive association with maladaptive coping (p

Abstract Much of what we know about terrestrial life during the Carboniferous Period comes from Middle Pennsylvanian (~315–307 Mya) Coal Measures deposited in low-lying wetland environments1–5. We know relatively little about terrestrial ecosystems from the Early Pennsylvanian, which was a critical interval for the diversification of insects, arachnids, tetrapods, and seed plants6–10. Here we report a diverse Early Pennsylvanian trace and body fossil Lagerstätte (~320–318 Mya) from the Wamsutta Formation of eastern North America, distinct from coal-bearing deposits, preserved in clastic substrates within basin margin conglomerates. The exceptionally preserved trace fossils and body fossils document a range of vertebrates, invertebrates and plant taxa (n = 131), with 83 distinct foliage morphotypes. Plant-insect interactions include what may be the earliest evidence of insect oviposition. This site expands our knowledge of early terrestrial ecosystems and organismal interactions and provides ground truth for future phylogenetic reconstructions of key plant, arthropod, and vertebrate groups.

Abstract Background The nursing workforce comprises multiple generations, each with unique values, beliefs, and expectations that can influence communication, work ethic, and professional relationships. In Qatar, the generational gap between nurses and nurse managers poses challenges to effective communication and teamwork, impacting job satisfaction and patient outcomes. Aim This study investigates the generational gap between nurses and nurse managers in Qatar, aiming to identify strategies to enhance collaboration and create a positive work environment. Methods A qualitative research design was used, involving semi-structured interviews with 20 participants, including frontline nurses and senior nurse managers. Participants were purposively sampled to represent different generations. Data were collected through face-to-face and virtual interviews, then transcribed and thematically analyzed. Findings Four key themes emerged: Optimizing the Work Environment: Older generations preferred transformational and situational leadership, while younger nurses valued respect, teamwork, accountability, and professionalism. Strengthening Work Atmosphere through Communication and values: Older nurses favored face-to-face communication, while younger nurses preferred digital tools. Cultivating Respect and Empathy: Younger nurses emphasized fairness in assignments and promotions, while older nurses focused on empathy and understanding. Dynamic Enhancement of Healthcare Systems: Younger nurses were more adaptable to technology and professional development, while older nurses prioritized clinical care and patient outcomes. Conclusion The study reveals significant generational differences in leadership preferences, communication styles, and adaptability to technology. Addressing these gaps through effective leadership, ongoing education, and open communication can improve job satisfaction and patient care.

Abstract Background Healthcare workers (HCWs) including community health extension workers (CHEWs) in the Federal Capital Territory, Nigeria participated in a hypertension training series following the Extension for Community Healthcare Outcomes (ECHO) model which leverages technology and a practical peer-to-peer learning framework to virtually train healthcare practitioners. We sought to evaluate the patient-level effects of the hypertension ECHO series. Methods HCWs from 12 of 33 eligible primary healthcare centers (PHCs) in the Hypertension Treatment in Nigeria Program (NCT04158154) were selected to participate in a seven-part hypertension ECHO series from August 2022 to April 2023. Concurrent Hypertension Treatment in Nigeria Program patient data were used to evaluate changes in hypertension treatment and control rates, and adherence to Nigeria’s hypertension treatment protocol. Outcomes were compared between the 12 PHCs in the ECHO program and the 21 which were not. Results Between July 2022 and June 2023, 16,691 PHC visits were documented among 4340 individuals (ECHO: n = 1428 [33%], non-ECHO: n = 2912 [67%]). Patients were on average (SD) 51.5 (12.0) years old, and one-third were male (n = 1372, 32%) with no differences between cohorts in either characteristic (p ≥ 0.05 for both). Blood pressures at enrollment were higher in the ECHO cohort compared to the non-ECHO cohort (systolic p

Abstract Background Prominent product placement is a core promotional tactic in retail food environments. How this practice has been adapted for online supermarkets, and the extent to which it is applied to healthier and less healthy food products in this setting, is largely unknown. We aimed to investigate placement-type promotions of food products in Australian online supermarkets. Methods We developed a new method to assess placement promotions and applied it to the online stores of the two largest supermarket retailers in Australia. Each online store was audited across six ‘locations’ (input prior to data collection), including a randomly selected high socio-economic position area and low socio-economic position area from each of the three largest Australian cities. The names, page locations and type of placement strategy of promoted food products were captured, with product healthiness assessed using the Health Star Rating (HSR) nutrient profiling system. Descriptive statistics summarised the page locations of promoted products and the placement strategies used to promote them, and chi-squared tests applied to compare product healthiness by retailer and socio-economic position. Results We recorded 12,152 food products promoted through placement strategies, 99% of which were eligible for a HSR. Overall, 44% of products promoted through placement strategies were unhealthy. Cross-promotions and recommendations was the most common strategy recorded overall (55.9% of all strategies), and advertisements and site content was the strategy most likely to promote unhealthy products (53.7% of products unhealthy). One retailer was more likely to promote unhealthy products (46% v 43%, p = 0.004) and unhealthy products were more likely to be promoted in more disadvantaged than less disadvantaged locations (45% vs 43%, p = 0.05), though the magnitudes of difference were small. Conclusions A considerable number of unhealthy products are likely presented to online grocery shoppers in Australia. Public health policies targeting unhealthy food promotions may need to be updated, including with consideration of the different ways that products can be prominently displayed online, to avoid exacerbating risks of diet-related disease and health inequalities. Our novel methodology could be used for ongoing monitoring of online supermarkets in Australia and elsewhere to inform such policies.

Abstract Integrated STEM education (iSTEM) is recognized for its potential to improve students’ scientific and mathematical knowledge, as well as to nurture positive attitudes toward STEM, which are essential for motivating students to consider STEM-related careers. While prior studies have examined the relationship between specific iSTEM activities or curricula and changes in student attitudes, research is lacking on how the aspects of iSTEM are operationalized and their influence on shifts in student attitudes towards STEM, especially when considering the role of demographic factors. Addressing this gap, our study applied multilevel modeling to analyze how different iSTEM aspects and demographic variables predict changes in student attitudes. Drawing on data from two five-year NSF-funded projects, we evaluated pre- and post-attitude survey responses from 948 students. Our analysis identified two key iSTEM aspects—relating content to students’ lives and engagement in engineering design—that significantly influence positive attitude change. The results highlight the importance of curriculum relevance and hands-on, problem-solving activities in shaping student attitudes. However, the impact of these instructional strategies varies across demographic groups. The study’s insights into the differential impact of iSTEM aspects on diverse student groups provide actionable guidance for educators, curriculum developers, and policymakers aiming to enhance STEM learning experiences and outcomes.

Abstract Introduction Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2. Methods This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample. Results 10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00–1.00) when candidemia was defined according to both methods. Conclusion Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.

Abstract Background Emerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life. We investigated the perspectives of parents about the anticipated utility and impact of predicting later autism diagnosis from a biomarker-based test in infancy. Methods Parents of infants were interviewed to ascertain receptiveness and perspectives on early (6-12 months) prediction of autism using emerging biomarker technologies. One group had experience parenting an older autistic child (n=30), and the other had no prior autism parenting experience (n=25). Parent responses were analyzed using inductive qualitative coding methods. Results Almost all parents in both groups were interested in predictive testing for autism, with some stating they would seek testing only if concerned about their infant’s development. The primary anticipated advantage of testing was to enable access to earlier intervention. Parents also described the anticipated emotions they would feel in response to test results, actions they might take upon learning their infant was likely to develop autism, attitudes towards predicting a child’s future support needs, and the potential impacts of inaccurate prediction. Conclusion In qualitative interviews, parents of infants with and without prior autism experience shared their anticipated motivations and concerns about predictive testing for autism in the first year of life. The primary reported motivators for testing—to have more time to prepare and intervene early—could be constrained by familial resources and service availability. Implications for ethical communication of results, equitable early intervention, and future research are discussed.

Abstract Background Single-cell chromatin accessibility assays, such as scATAC-seq, are increasingly employed in individual and joint multi-omic profiling of single cells. As the accumulation of scATAC-seq and multi-omics datasets continue, challenges in analyzing such sparse, noisy, and high-dimensional data become pressing. Specifically, one challenge relates to optimizing the processing of chromatin-level measurements and efficiently extracting information to discern cellular heterogeneity. This is of critical importance, since the identification of cell types is a fundamental step in current single-cell data analysis practices. Results We benchmark 8 feature engineering pipelines derived from 5 recent methods to assess their ability to discover and discriminate cell types. By using 10 metrics calculated at the cell embedding, shared nearest neighbor graph, or partition levels, we evaluate the performance of each method at different data processing stages. This comprehensive approach allows us to thoroughly understand the strengths and weaknesses of each method and the influence of parameter selection. Conclusions Our analysis provides guidelines for choosing analysis methods for different datasets. Overall, feature aggregation, SnapATAC, and SnapATAC2 outperform latent semantic indexing-based methods. For datasets with complex cell-type structures, SnapATAC and SnapATAC2 are preferred. With large datasets, SnapATAC2 and ArchR are most scalable.

Abstract Objectives Older adults are more likely to have poor sleep quality and be socially isolated. The present study examined the potential benefits and disadvantages of social media use (SMU) with respect to sleep quality and perceived social isolation among Iranian late-middle-aged and older adults with focus a on both the mediating and moderating role of psychological distress. Methods A population-based cross-sectional study was conducted among 900 older community-dwellers living in Shiraz using a structured questionnaire. Social media use was assessed by estimating the frequency of social networking site visits per week. Data concerning self-rated physical health, chronic medical and mental health conditions, perceived social isolation, sleep quality, and psychological distress were also collected. Multiple linear regression was used to identify independent variables associated with outcomes. Then, mediation and moderation models were used to examine the potential mediating and moderating effects of psychological distress and SMU on their relationships with the study variables. Results Higher social media use was associated with better sleep quality and less perceived social isolation. Nevertheless, the relationships between SMU and participants’ sleep quality and perceived social isolation were largely mediated by their level of psychological distress. Furthermore, SMU had a significant moderating effect in the relationship between the psychological distress and the levels of perceived social isolation, so that participants with higher frequency of SMU per week felt less loneliness. Conclusions The study findings suggest that SMU has a positive buffering effect regarding late middle-aged and older adults’ mental health mainly through moderation of their perceived social isolation. The mediating role of psychological distress in research examining the relationship between SMU and older adults’ mental health outcomes should be considered in future research.

Abstract Elucidating physical transport phenologies in large lakes can aid understanding of larval recruitment dynamics. Here, we integrate a series of climate, hydrodynamic, biogeochemical, and Lagrangian particle dispersion models to: (1) simulate hatch and transport of fish larvae throughout an illustrative large lake, (2) evaluate patterns of historic and potential future climate‐induced larval transport, and (3) consider consequences for overlap with suitable temperatures and prey. Simulations demonstrate that relative offshore transport increases seasonally, with shifts toward offshore transport occurring earlier during relatively warm historic and future simulations. Intra‐ and inter‐annual trends in transport were robust to assumed pelagic larval duration and precise location and timing of hatching. Larvae retained nearshore generally encountered more favorable temperatures and zooplankton densities compared to larvae transported offshore. Larval exploitation of nearshore resources under climate change may depend on a concomitant shift to earlier spawning and hatch times in advance of earlier offshore transport.

Abstract The cellular response to cisplatin was assessed in human osteosarcoma cells, using synchrotron-based (SR) Fourier Transform InfraRed nanospectroscopy (nano-FTIR) at the MIRIAM beamline B22 of Diamond Light Source (UK). This label-free mapping method delivered simultaneous morphological and biochemical information on a subcellular level (i.e. 100 s nanometer or better). Based on specific spectral biomarkers, the main biochemical constituents affected by the drug were identified at distinct locations within the cell´s inner body. Cisplatin was shown to have a noteworthy effect on proteins, mostly within the cytoplasm. A clear drug impact on cellular lipids was also observed. Within current literature on s-SNOM, this nanospectroscopy work represents a first successful application in life sciences providing full fingerprint nano-FTIR spectra across intact human cancer cells.

Abstract Hypertension poses a significant health burden globally. In Nigeria, hypertension prevalence is on the rise, with low rates of awareness, treatment, and control. This policy brief explores the critical gaps addressed by the Hypertension Treatment in Nigeria (HTN) Program, highlighting its strengths, initial outcomes, and scalability in primary care settings. The HTN Program employs an integrated, multilevel care model based on the World Health Organization’s HEARTS technical package, including patient registration and empanelment, team-based care, training and supervision, a standardized treatment protocol, a health information management system, and a drug revolving fund to improve medication accessibility. By December 2023, hypertension treatment and control rates reached surpassing 90% and 50%, respectively, thus underscoring the program’s impact. The HTN Program serves as a model for delivering integrated hypertension care in primary care. Results should be leveraged for political commitment and financing to evaluate and manage non-communicable diseases such as hypertension in primary care through federal and state primary health development agencies. Furthermore, incorporating metrics related to hypertension control and treatment into the Integrated Supportive Management Information System can enhance routine monitoring and evaluation.

Abstract Houseflies provide a good experimental model to study the initial evolutionary stages of a primary sex-determining locus because they possess different recently evolved proto-Y chromosomes that contain male-determining loci (M) with the same male-determining gene, Mdmd. We investigate M-loci genomically and cytogenetically revealing distinct molecular architectures among M-loci. M on chromosome V (M V ) has two intact Mdmd copies in a palindrome. M on chromosome III (M III ) has tandem duplications containing 88 Mdmd copies (only one intact) and various repeats, including repeats that are XY-prevalent. M on chromosome II (M II ) and the Y (M Y ) share M III -like architecture, but with fewer repeats. M Y additionally shares M V -specific sequence arrangements. Based on these data and karyograms using two probes, one derives from M III and one Mdmd-specific, we infer evolutionary histories of polymorphic M-loci, which have arisen from unique translocations of Mdmd, embedded in larger DNA fragments, and diverged independently into regions of varying complexity.

Abstract In everyday life, people need to respond appropriately to many types of emotional stimuli. Here, we investigate whether human occipital-temporal cortex (OTC) shows co-representation of the semantic category and affective content of visual stimuli. We also explore whether OTC transformation of semantic and affective features extracts information of value for guiding behavior. Participants viewed 1620 emotional natural images while functional magnetic resonance imaging data were acquired. Using voxel-wise modeling we show widespread tuning to semantic and affective image features across OTC. The top three principal components underlying OTC voxel-wise responses to image features encoded stimulus animacy, stimulus arousal and interactions of animacy with stimulus valence and arousal. At low to moderate dimensionality, OTC tuning patterns predicted behavioral responses linked to each image better than regressors directly based on image features. This is consistent with OTC representing stimulus semantic category and affective content in a manner suited to guiding behavior.

Abstract Recent advances in haptic technology could allow haptic hearing aids, which convert audio to tactile stimulation, to become viable for supporting people with hearing loss. A tactile vocoder strategy for audio-to-tactile conversion, which exploits these advances, has recently shown significant promise. In this strategy, the amplitude envelope is extracted from several audio frequency bands and used to modulate the amplitude of a set of vibro-tactile tones. The vocoder strategy allows good consonant discrimination, but vowel discrimination is poor and the strategy is susceptible to background noise. In the current study, we assessed whether multi-band amplitude envelope expansion can effectively enhance critical vowel features, such as formants, and improve speech extraction from noise. In 32 participants with normal touch perception, tactile-only phoneme discrimination with and without envelope expansion was assessed both in quiet and in background noise. Envelope expansion improved performance in quiet by 10.3% for vowels and by 5.9% for consonants. In noise, envelope expansion improved overall phoneme discrimination by 9.6%, with no difference in benefit between consonants and vowels. The tactile vocoder with envelope expansion can be deployed in real-time on a compact device and could substantially improve clinical outcomes for a new generation of haptic hearing aids.

Abstract Introduction Noncommunicable diseases (NCDs) are associated with high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of National policy, Nigeria has committed to implement the World Health Organization (WHO) Package of Essential Non-communicable Disease interventions for primary care. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems (HMIS), equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the DM component of the WHO package, and the readiness of the health workers in these PHCs to implement a DM screening, evaluation, and management program to inform future adoption and implementation. Methods This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August and October 2021. The SARA tool was adapted to focus on DM services and the availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. Results All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] = 5 [4–9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1–4]. At least one staff member was recently trained in DM care in 11 PHCs (36%). The study also reported high availability of paper-based HMIS (100%), and DM screening services using a glucometer (87%), but low availability of DM job aids (27%), treatment (23%), and national guidelines/protocols (0%). Conclusion This formative assessment of PHCs’ readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs regarding equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and supply essential DM medications.

Assessing the pathogenicity of a disease-associated genetic variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect inclusion or exclusion of animals and compromise the long-term health of a population, and at the level of the individual animal, lead to incorrect treatment and even life-ending decisions. Criteria to determine pathogenicity are not standardized, i.e., no guidelines for animal variants are available. Here, we aimed to develop and validate guidelines to be used by the community for Mendelian disorders in domestic animals to classify variants in categories based on standardized criteria. These so-called animal variant classification guidelines (AVCG) were based on those developed for humans by The American College of Medical Genetics and Genomics (ACMG). In a direct comparison, 83% of the pathogenic variants were correctly classified with ACMG, while this increased to 92% with AVCG. We described methods to develop datasets for benchmarking the criteria and identified the most optimal in silico variant effect predictor tools. As the reproducibility was high, we classified 72 known disease-associated variants in cats and 40 other disease-associated variants in eight additional species.

During the COVID-19 pandemic, the fear of COVID-19 increased, especially among nurses. The present study investigated the effect of in-person and virtual methods of Eye Movement Desensitization and Reprocessing (EMDR) on the fear of COVID-19 among nurses. In a three-armed randomized control trial, the sample comprised 141 nurses working in hospitals affiliated to Qazvin University of Medical Sciences, Qazvin, Iran. Eligible individuals were randomly assigned in study groups (virtual EMDR, in-person EMDR, and control) using balanced block method with a block size of six. The main outcome of the study was the fear of COVID-19 assessed before, immediately after, and three months after intervention. The secondary outcomes assessed included anxiety, depression and work-related quality of life assessed before and three months after the intervention. The results of variance-covariance analysis for repeated measures showed a significant reduction in the mean score fear of COVID-19 immediately after and three months after the intervention in the in-person EMDR intervention group compared to the virtual group (mean difference equal to -3.48 and -3.57) and the control group (mean difference equal to -5.45 and -5.57). Considering the minimum clinically significant difference was equal to 2.54 on the Fear of COVID-19 Scale, this reduction was also clinically significant. The average number of intervention sessions was two. No significant difference was observed regarding anxiety, depression and work-related quality of life after intervention between all three groups. In-person EMDR is more effective than the virtual EMDR as a non-pharmacological method in the treatment of fear of COVID-19 among nurses. In-person EMDR should be conducted in preference to virtual EMDR. However, in situations where in-person EMDR cannot be conducted, virtual EMDR could be considered as a potential alternative.

Summary: Background: Between 1% and 4% of febrile infants, aged from birth to 90 days of age, presenting to hospital will be diagnosed with an invasive bacterial infection (IBI). Traditional teaching has advocated a treat all approach but more recently a number of clinical decision aids (CDA) have been developed to classify febrile infants into lower and higher risk cohorts, with lower risk infants suitable for management without immediate parenteral antibiotics and lumbar puncture. The aim of this study was to apply these CDA to a UK and Irish cohort. Methods: This was a prospective multicentre cohort study of febrile infants presenting to 35 Paediatric Emergency Research in the UK and Ireland (PERUKI) sites between the 6th July 2022 and the 31st August 2023. All infants received standard care as per local policy. IBI was defined as growth of bacterial pathogen in blood or cerebrospinal fluid. The performance of the following CDAs were assessed, National Institute for Health and Care Excellence (NICE) guidelines NG143 (Fever under 5 years), British Society Antimicrobial Chemotherapy (BSAC), Aronson rule and American Academy of Pediatrics (AAP) CDA. A cost comparison of each CDA against a treat all approach was conducted. Trial registration: NCT05259683. Findings: 1821 were included in the final analysis. The median age was 46 days (IQR: 30–64 days), with 1108 (61%) being male. Of the 1821 infants, 67 (3.7%) had IBI. The AAP and BSAC CDAs were the most sensitive at 0.99 (95% CI 0.92–1.0) for both with specificities of 0.23 (95% CI 0.21–0.25) and 0.20 (95% CI 0.18–0.22) respectively. The NICE NG143 and Aronson CDA were the most specific CDAs with values of 0.27 (95% CI 0.25–0.30) and 0.30 (95% CI 0.28–0.32) respectively, but their sensitivity was lower. The AAP CDA performed equally well with either procalcitonin (PCT) or C-reactive protein (CRP) as the biomarker of choice. Of the 1821 infants, 77% were admitted, 14% were discharged and 9% were ambulated. All CDAs were cost saving for hospital services when compared to a treat all approach, with the lowest mean cost per patient estimated for Aronson (£1171; bootstrap 95% CI £1129–£1214) and NICE NG143 CDA (£1218; bootstrap 95% CI £1174–£1263). Interpretation: The AAP and BSAC CDAs are highly sensitive at excluding IBI, with a cost saving to hospital services when compared to a treat all approach. The substitution of CRP for PCT made no difference to the performance of the AAP CDA in this cohort and was more costly. Funding: The Febrile Infant Diagnostic Assessment and Outcome (FIDO) study is funded by Royal College of Emergency Medicine Doctoral Fellowship (RCEM 02/03/2021). Procalcitonin analysis was supported by the Public Health Agency Northen Ireland Grant (HSC R&D-COM/5745/22). The funders played no part in the conception or design of this study.

An outbreak of monkeypox (Mpox) appeared suddenly and rapidly spread worldwide during 2022. Men who have sex with men (MSM) are at a high risk of contracting Mpox compared to other cohorts. The present study examined the psychometric properties of a newly developed scale among MSM: the Motors of Mpox Vaccination Acceptance Scale (MoMVA) assessing cognitive components of the motivation to receive an Mpox vaccination. In total, 389 MSM participated in an online survey study. The factor structures of the MoMVA were first examined using exploratory factor analysis. After determining the factor structures, the MoMVA was further examined for: (i) internal consistency using Cronbach’s α; (ii) concurrent validity using correlations with risk perception of contracting Mpox and intention to receive an Mpox vaccination; and (iii) known-group validity by comparing the scores of the MoMVA between MSM who vaccinated and those who did not. The results indicated that the MoMVA had a two-factor structure (positive and negative motors). The MoMVA had acceptable internal consistency (α = 0.793 to 0.914), concurrent validity (associated with intention to receive an Mpox vaccination), and known-group validity (participants who vaccinated had higher MoMVA scores than those who did not). The results of the present study indicated that the psychometric properties of the MoMVA were good and that they can be used for assessing cognitive components of the motivation to receive an Mpox vaccination among MSM.

Background: Anxiety is a common psychological disorder in school-aged children and adolescents. The present study aimed to assess the prevalence of anxiety symptoms and sleep disturbances and their relationship with academic achievement among female students in Herat, Afghanistan. Methods: A cross-sectional survey of 737 female students (mean age 11.8 years old) was conducted across 10 randomly selected schools in Herat, Afghanistan, covering Grades 1 to 6. Students were randomly chosen within these schools. The Depression Anxiety Stress Scale for Youth (DASS-Y) and Pittsburgh Sleep Quality Index (PSQI) assessed anxiety and sleep disturbance, while academic achievement ratings were provided by schoolteachers. Results: Using the DASS-Y and the PSQI, 65.5% reported anxiety symptoms and 46.4% reported sleep disturbance. Low academic achievement correlated significantly with anxiety (r = 0.228) and sleep issues (r = 0.161). Multiple logistic regression analysis identified predictors for anxiety and sleep disturbance. Predictors for anxiety included being aged 13–16 years, having lower class grade, being of low economic status, and having unemployed parents. Predictors for sleep disturbance included being aged 13–16 years, having lower class grade, having an uneducated father, being of low economic status, and having unemployed parents. Conclusion: There is a high prevalence of anxiety symptoms and sleep disturbances among female school students in Herat, Afghanistan. Significant correlations exist between students' academic achievement, anxiety, and sleep disturbances. Addressing anxiety and sleep disturbances among Afghan female school students could be facilitated by revising current government policies concerning students' health. Educational campaigns focused on sleep hygiene and anxiety management for both students and their parents may also prove beneficial.

Numerous studies suggest a negative impact of problematic internet use (PIU) not only on mental health but also on somatic components of adolescent health. The present study aimed to identify the associations between different types of PIU – generalized PIU (GPIU), problematic video game use (PVGU), and problematic social media use (PSMU) – and recurrent pain symptoms (headache, abdominal pain, and back pain), as well as to determine the role of psychosocial factors in these associations. In a cross-sectional school-based study, 4411 urban Siberian adolescents were asked about the presence, frequency, and intensity of pain symptoms in the past three months. Standardized psychometric scales were used to assess GPIU, PSMU and PVGU. Given the presence of psychosocial problems as a major confounder, direct associations of PSMU and GPIU with recurrent pain symptoms (headache, abdominal pain, and back pain) were found. PVGU was weakly associated only with abdominal pain. Further analysis indicated that the positive associations were largely mediated by comorbid psychosocial problems. These findings highlight the importance of addressing both problematic internet use and comorbid psychosocial problems to effectively reduce PIU-associated recurrent headaches, abdominal pain, and back pain among adolescents.

Objective Emotional labour is expected, especially from service sector employees, to ensure customer satisfaction and meet corporate expectations. Previous studies have mainly focused on the effects of emotional labour on employees. Few studies have examined its predictors in terms of personality traits. In the present study, the predictive levels of the Big Five and dark triad traits on emotional labour were examined possibly for the first time.Method Four hundred and seventy-three service sector employees participated in the research. Data were collected using an online survey comprising questions relating to the Big Five personality traits, dark triad personality traits, emotional labour and personal (demographic) information. Descriptive statistics, internal consistency test, Pearson’s correlation and hierarchical regression were used to analyse the data.Results According to the findings, Machiavellianism was the strongest predictor of surface acting, and agreeableness was the strongest predictor of deep acting and naturally felt emotions. Narcissism was found to be a predictor of surface acting.Conclusions As a result of examining the Big Five and dark triad traits in predicting emotional labour styles, the fact that agreeableness predicted deep acting and naturally felt emotions suggests that agreeableness should be given closer attention in recruitment and promotion decisions, especially in the service sector.

This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.

Mukbang watching (i.e., watching eating broadcasts) is an emerging online behaviour that has recently gained popularity. Although, there are a number of positive impacts of recreational mukbang watching (e.g., helping overcome loneliness), for a minority of individuals, excessive mukbang watching may turn into problematic (i.e., addictive) mukbang watching and lead to negative consequences. The present study investigated the addictive symptoms of mukbang watching using a qualitative design. The study attempted to determine the addictive symptoms of mukbang watching through semi-structured interviews with a sample of eight mukbang viewers who frequently watched mukbang. Directed content analysis was used to analyse the data. Nine key themes were explored comprising preoccupation, withdrawal, tolerance, inability to stop, loss of interest, continuing despite problems, deceiving family/friends, relieving negative mood, and risking relationships. Findings of the present study concur with those of previous survey research suggesting that mukbang watching may be another online addictive behaviour that can result in adverse consequences for individuals’ mental, social, and physical health.

Background: Teachers in demanding work environments are prone to anxiety, depression, and stress. Validated measures across different cultural contexts are required. The present study evaluated the psychometric properties of the 21-item Depression, Anxiety and Stress Scale (DASS-21) and DASS-12 and DASS-8 among Spanish and Chinese primary school teachers. Methods: A total of 3930 primary school teachers were recruited, comprising samples from Spain (n = 1350) and China (n = 2580). Scale structure was analyzed using confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM). Model comparisons were conducted to identify the best-fitting factor structure. Convergent and discriminant validity were examined, and concurrent validity was assessed using emotional exhaustion as a criterion variable. Optimal diagnostic thresholds were established through latent profile analysis (LPA) and receiver operating characteristic (ROC) analysis. Results: Among the tested factor structures (unidimensional, oblique three-factor, ESEM, bifactor, and bifactor ESEM models), the ESEM model demonstrated superior fit indices, supporting acceptable factorial validity among both Spanish and Chinese samples. The DASS versions in the ESEM structure exhibited strong convergent, discriminant, and concurrent validity in the Spanish sample, while showing relatively weaker validity indices among the Chinese sample. Notably, the empirically derived cutoff scores for DASS-21 sub-dimensions among teachers were substantially higher than the originally recommended thresholds. Conclusion: The three DASS versions effectively assessed three types of psychological distress among Spanish teachers, while among the Chinese teachers, the DASS instruments appeared useful for assessing distress, though caution is recommended when using individual subscale scores.