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BACKGROUND: The three-item Sexual Distress Scale (SDS-3) has been frequently used to assess distress related to sexuality in public health surveys and research on sexual wellbeing. However, its psychometric properties and measurement invariance across cultural, gender and sexual subgroups have not yet been examined. This multinational study aimed to validate the SDS-3 and test its psychometric properties, including measurement invariance across language, country, gender identity, and sexual orientation groups. METHODS: We used global survey data from 82,243 individuals (Mean age=32.39 years; 40.3 % men, 57.0 % women, 2.8 % non-binary, and 0.6 % other genders) participating in the International Sexual Survey (ISS; https://internationalsexsurvey.org/) across 42 countries and 26 languages. Participants completed the SDS-3, as well as questions regarding sociodemographic characteristics, including gender identity and sexual orientation. RESULTS: Confirmatory factor analysis (CFA) supported a unidimensional factor structure for the SDS-3, and multi-group CFA (MGCFA) suggested that this factor structure was invariant across countries, languages, gender identities, and sexual orientations. Cronbachs α for the unidimensional score was 0.83 (range between 0.76 and 0.89), and McDonalds ω was 0.84 (range between 0.76 and 0.90). Participants who did not experience sexual problems had significantly lower SDS-3 total scores (M = 2.99; SD=2.54) compared to those who reported sexual problems (M = 5.60; SD=3.00), with a large effect size (Cohens d = 1.01 [95 % CI=-1.03, -0.98]; p < 0.001). CONCLUSION: The SDS-3 has a unidimensional factor structure and appears to be valid and reliable for measuring sexual distress among individuals from different countries, gender identities, and sexual orientations.

Abstract Background Limited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts. Methods Thirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT. Results While alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R 2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism. Conclusions This study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes. Trial registration Clinicaltrials.gov NCT02185274.

Abstract Mitochondria are highly dynamic organelles which undergo constant fusion and fission as part of the mitochondrial quality control. In genetic diseases and age-related neurodegenerative disorders, altered mitochondrial fission-fusion dynamics have been linked to impaired mitochondrial quality control, disrupted organelle integrity and function, thereby promoting neural dysfunction and death. The key enzyme regulating mitochondrial fission is the GTPase Dynamin-related Protein 1 (Drp1), which is also considered as a key player in mitochondrial pathways of regulated cell death. In particular, increasing evidence suggests a role for impaired mitochondrial dynamics and integrity in ferroptosis, which is an iron-dependent oxidative cell death pathway with relevance in neurodegeneration. In this study, we demonstrate that CRISPR/Cas9-mediated genetic depletion of Drp1 exerted protective effects against oxidative cell death by ferroptosis through preserved mitochondrial integrity and maintained redox homeostasis. Knockout of Drp1 resulted in mitochondrial elongation, attenuated ferroptosis-mediated impairment of mitochondrial membrane potential, and stabilized iron trafficking and intracellular iron storage. In addition, Drp1 deficiency exerted metabolic effects, with reduced basal and maximal mitochondrial respiration and a metabolic shift towards glycolysis. These metabolic effects further alleviated the mitochondrial contribution to detrimental ROS production thereby significantly enhancing neural cell resilience against ferroptosis. Taken together, this study highlights the key role of Drp1 in mitochondrial pathways of ferroptosis and expose the regulator of mitochondrial dynamics as a potential therapeutic target in neurological diseases involving oxidative dysregulation.

Abstract Biodiversity and functioning often follow spatial gradients, yet with unclear causal linkage. In spatially complex rivers, regional-scale factors associated with hydrological connections and catchment properties control downstream transport of material and dispersal of organisms, both being crucial for ecosystem functioning. In a single snapshot study, we here show how a river’s network structure interacts with its terrestrial matrix to control key environmental conditions and periphyton community composition at the local habitat scale, which in turn drive primary production. We found the high geodiversity of the Vjosa River network to promote high periphyton beta-biodiversity through regional (dispersal) and local (species sorting) processes. Community turnover driven by species sorting rather than purely by dispersal was identified as relevant for production rates, suggesting a match between environment and community composition to be conditional for functioning. Hence, anthropogenic perturbation of regional mechanisms by river modification may affect ecosystem functions through interfering with metacommunity structure.

Abstract COSINUS is a dark matter (DM) direct search experiment that uses sodium iodide (NaI) crystals as cryogenic calorimeters. Thanks to the low nuclear recoil energy threshold and event-by-event discrimination capability, COSINUS will address the long-standing DM claim made by the DAMA/LIBRA collaboration. The experiment is currently under construction at the Laboratori Nazionali del Gran Sasso, Italy, and employs a large cylindrical water tank as a passive shield to meet the required background rate. However, muon-induced neutrons can mimic a DM signal therefore requiring an active veto system, which is achieved by instrumenting the water tank with an array of photomultiplier tubes (PMTs). This study optimizes the number, arrangement, and trigger conditions of the PMTs as well as the size of an optically invisible region. The objective was to maximize the muon veto efficiency while minimizing the accidental trigger rate due to the ambient and instrumental background. The final configuration predicts a veto efficiency of 99.63 ± 0.16% and 44.4 ± 5.6% in the tagging of muon events and showers of secondary particles, respectively. The active veto will reduce the cosmogenic neutron background rate to 0.11 ± 0.02 cts $$\cdot $$ · kg $$^{-1}\cdot $$ - 1 · year $$^{-1},$$ - 1 , corresponding to less than one background event in the region of interest for the whole COSINUS-1 $$\pi $$ π exposure of 1000 kg $$\cdot $$ · days.

Abstract There is an ongoing debate about anxiety deficits in psychopathy and their possible impact on individual behavior. Data on actual anxiety- and threat-related behavior associated with psychopathy is still limited. We performed a mixed reality study using the elevated plus-maze (EPM) in a non-clinical sample (N = 160) to test anxiety-related behavior in relation to psychopathic personality traits measured through the Brief Questionnaire of Psychopathic Personality Traits (FPP). The psychopathy sum score correlated significantly with all measures of anxiety-related behavior on the EPM. Sensation seeking, but not general levels of acrophobia was moreover associated with psychopathic traits. Multivariate analyses revealed that the subscales Fearlessness and Lack of Empathy of the FPP predicted anxious behavior. Our findings are the first to demonstrate the relationship between psychopathic traits and actual behavior in an anxiety-inducing environment. This supports the low-anxiety hypothesis in psychopathy research. Implications for potentially harmful or risky behavior are discussed.

Abstract Background The demand for mental health services in Australia is substantial and has grown beyond the capacity of the current workforce. As a result, it is currently difficult for many to access secondary healthcare providers. Within the secondary healthcare sector, however, peer workers who have lived experience of managing mental health conditions have been increasingly employed to intentionally use their journey of recovery in supporting others living with mental health conditions and their communities. Currently, the presence of peer workers in primary care has been limited, despite the potential benefits of providing supports in conjunction with GPs and secondary healthcare providers. Methods This stepped-wedge cluster randomised controlled trial (RCT) aims to evaluate a lived experience peer support intervention for accessing mental health care in primary care (PS-PC). Four medical practices across Australia will be randomly allocated to switch from control to intervention, until all practices are delivering the PS-PC intervention. The study will enrol 66 patients at each practice (total sample size of 264). Over a period of 3–4 months, 12 h of practical and emotional support provided by lived experience peer workers will be available to participants. Scale-based questionnaires will inform intervention efficacy in terms of mental health outcomes (e.g., self-efficacy) and other health outcomes (e.g., healthcare-related costs) over four time points. Other perspectives will be explored through scales completed by approximately 150 family members or carers (carer burden) and 16 peer workers (self-efficacy) pre- and post-intervention, and 20 medical practice staff members (attitudes toward peer workers) at the end of each study site’s involvement in the intervention. Interviews (n = 60) and six focus groups held toward the end of each study site’s involvement will further explore the views of participants, family members or carers, peer workers, and practice staff to better understand the efficacy and acceptability of the intervention. Discussion This mixed-methods, multi-centre, stepped-wedge controlled study will be the first to evaluate the implementation of peer workers in the primary care mental health care sector. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12623001189617. Registered on 17 November 2023, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386715

BACKGROUND AND AIMS: Despite its inclusion in the 11th revision of the International Classification of Diseases, there is a virtual paucity of high-quality scientific evidence about compulsive sexual behavior disorder (CSBD), especially in underrepresented and underserved populations. Therefore, we comprehensively examined CSBD across 42 countries, genders, and sexual orientations, and validated the original (CSBD-19) and short (CSBD-7) versions of the Compulsive Sexual Behavior Disorder Scale to provide standardized, state-of-the-art screening tools for research and clinical practice. METHOD: Using data from the International Sex Survey (N = 82,243; Mage = 32.39 years, SD = 12.52), we evaluated the psychometric properties of the CSBD-19 and CSBD-7 and compared CSBD across 42 countries, three genders, eight sexual orientations, and individuals with low vs. high risk of experiencing CSBD. RESULTS: A total of 4.8% of the participants were at high risk of experiencing CSBD. Country- and gender-based differences were observed, while no sexual-orientation-based differences were present in CSBD levels. Only 14% of individuals with CSBD have ever sought treatment for this disorder, with an additional 33% not having sought treatment because of various reasons. Both versions of the scale demonstrated excellent validity and reliability. DISCUSSION AND CONCLUSIONS: This study contributes to a better understanding of CSBD in underrepresented and underserved populations and facilitates its identification in diverse populations by providing freely accessible ICD-11-based screening tools in 26 languages. The findings may also serve as a crucial building block to stimulate research into evidence-based, culturally sensitive prevention and intervention strategies for CSBD that are currently missing from the literature.

BACKGROUND AND AIMS: The World Health Organizations International Classification of Diseases (ICD-11) includes Compulsive Sexual Behavior Disorder (CSBD), a new diagnosis that is both controversial and groundbreaking, as it is the first diagnosis to codify a disorder related to excessive, compulsive, and out-of-control sexual behavior. The inclusion of this novel diagnosis demonstrates a clear need for valid assessments of this disorder that may be quickly administered in both clinical and research settings. DESIGN: The present work details the development of the Compulsive Sexual Behavior Disorder Diagnostic Inventory (CSBD-DI) across seven samples, four languages, and five countries. SETTING: In the first study, data were collected in community samples drawn from Malaysia (N = 375), the U.S. (N = 877), Hungary (N = 7,279), and Germany (N = 449). In the second study, data were collected from nationally representative samples in the U.S. (N = 1,601), Poland (N = 1,036), and Hungary (N = 473). FINDINGS: Across both studies and all samples, results revealed strong psychometric qualities for the 7-item CSBD-DI, demonstrating evidence of validity via correlations with key behavioral indicators and longer measures of compulsive sexual behavior. Analyses from nationally representative samples revealed residual metric invariance across languages, scalar invariance across gender, strong evidence of validity, and utility in classifying individuals who self-identified as having problematic and excessive sexual behavior, as evidenced by ROC analyses revealing suitable cutoffs for a screening instrument. CONCLUSION: Collectively, these findings demonstrate the cross-cultural utility of the CSBD-DI as a novel measure for CSBD and provide a brief, easily administrable instrument for screening for this novel disorder.

Abstract Social decisions are influenced by a person’s social preferences. High psychopathy is defined by antisocial behaviour, but the relationship between psychopathy and social preferences remains unclear. In this study, we used a battery of economic games to study social decision-making and social preferences in relation to psychopathy in a sample of 35 male prison inmates, who were arrested for sexual and severe violent offenses (mean age = 39 years). We found no evidence for a relationship between social preferences (measured with the Dictator and Ultimatum Games, Social Value Orientation, and one-shot 2 × 2 games) and psychopathy (measured by the overall Hare Psychopathy Checklist-Revised score and both factors). These results are surprising but also difficult to interpret due to the small sample size. Our results contribute to the ongoing debate about psychopathy and social decision-making by providing crucial data that can be combined with future datasets to reach large sample sizes that can provide a more nuanced understanding about the relationship between psychopathy and social preferences.

Abstract Carbon dioxide removal is key to climate change mitigation, yet implications of its deployment remain unclear. Recent exponential growth in literature is rapidly filling this gap but makes the synthesis of the evidence on carbon dioxide removal side effects increasingly challenging. Here we address this issue by mapping this literature and proposing a taxonomy to synthesize and compare evidence on carbon dioxide removal side effects. The expansive evidence warrants the use of machine learning to systematically select relevant research and provide an inventory of nearly 400 co-benefits, challenges, and limits. We find rich evidence in Europe but little information for Africa, South America, and Oceania, where large-scale carbon dioxide removal is nevertheless projected. There is a predominance of articles discussing negative effects compared to positive ones. Starting from the limitations of our analysis and literature gaps, we provide entry points for future studies that can build on our literature-based taxonomy.

Abstract Background Sexual risk behavior in patients diagnosed with borderline personality disorder (BPD) is supposed to be associated with traumatic experiences and dissociative symptoms. Nevertheless, scientific research thereon is scarce which might be due to the high prevalence of sexual trauma and fear of overwhelming patients with explicit sexual content. Methods We investigated a clinical sample of patients diagnosed with BPD (n = 114) and compared them to a sample of matched healthy controls (HC) (n = 114) concerning the dissociative symptoms derealization, depersonalization, and conversion in sexual situations. In a subgroup of patients with BPD (n = 41) and matched HC (n = 40) dissociative symptoms after exposure to an acoustically presented erotic narrative were assessed in the lab. Regression analyses were used to examine the associations between sexual trauma, post-traumatic stress disorder (PTSD), dissociation in sexual situations, and risky sexual behavior. Results Patients diagnosed with BPD endorsed higher dissociative symptoms in sexual situations retrospectively and in the lab compared to HC. Regression analyses revealed that depersonalization and conversion symptoms in sexual situations were explained by severity of BPD, while derealization was explained by PTSD symptomatology. Impulsive and sexual behavior with an uncommitted partner were higher in the BPD group and explained by derealization, while conversion showed an inverse association. Conclusion Our findings highlight the importance of addressing distinct dissociative symptoms in sexual situations when counselling and treating women with BPD. In the long term, this could contribute to a reduction in sexual risk behavior in patients with BPD. Trial registration This analysis is part of a larger ongoing study and was registered prior to accessing the data (Registration trial DRKS00029716).

Non-technical summary: We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. Technical summary The IPCC Assessment Reports offer the scientific foundation for international climate negotiations and constitute an unmatched resource for climate change researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding across diverse climate change research communities, we have streamlined an annual process to identify and synthesise essential research advances. We collected input from experts on different fields using an online questionnaire and prioritised a set of ten key research insights with high policy relevance. This year we focus on: (1) looming overshoot of the 1.5°C warming limit, (2) urgency of phasing-out fossil fuels, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future of natural carbon sinks, (5) need for join governance of biodiversity loss and climate change, (6) advances in the science of compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. We first present a succinct account of these Insights, reflect on their policy implications, and offer an integrated set of policy relevant messages. This science synthesis and science communication effort is also the basis for a report targeted to policymakers as a contribution to elevate climate science every year, in time for the UNFCCC COP. Social media summary We highlight recent and policy-relevant advances in climate change research - with input from more than 200 experts 1.

We describe a previously unappreciated role for Bruton's tyrosine kinase (BTK) in fungal immune surveillance against aspergillosis, an unforeseen complication of BTK inhibitors (BTKi) used for treating B cell lymphoid malignancies. We studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, patients who were treated with BTKi, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and Fc[gamma]R-dependent manner, triggering the oxidative burst. BTK inhibition selectively impeded neutrophil-mediated damage to Aspergillus hyphae, primary granule release, and the fungus-induced oxidative burst by abrogating NADPH oxidase subunit [p40.sup.phox] and GTPase RAC2 activation. Moreover, neutrophil-specific Btk deletion in mice enhanced aspergillosis susceptibility by impairing neutrophil function, not recruitment or lifespan. Conversely, GM-CSF partially mitigated these deficits by enhancing [p47.sup.phox] activation. Our findings underline the crucial role of BTK signaling in neutrophils for antifungal immunity and provide a rationale for GM-CSF use to offset these deficits in patients who are susceptible., Introduction Invasive aspergillosis (IA), most often caused by the ubiquitous inhaled mold Aspergillus fumigatus, is an opportunistic fungal infection that exploits numeric or functional neutrophil defects (1-3). IA affects over [...]