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Objective: This study aimed to evaluate the reliability and validity of the Binge Eating Disorder Screener-7 (BEDS-7) across 42 countries and 26 languages, assessing its reliability and validity as a screening tool for binge-eating disorder (BED) in diverse cultural contexts. Specifically, it sought to enhance early recognition of BED symptoms in primary care settings globally, contributing to a standardized framework for assessing BED., Method: The International Sex Survey, a cross-sectional online study, was conducted in 42 countries and 26 languages. A diverse community sample of 82,243 participants, aged 18 years or older, completed the BEDS-7 and measures of sexuality, mental health, substance use, and sociodemographic characteristics. Confirmatory factor analyses and tests of measurement invariance were employed to evaluate the reliability and validity of the BEDS-7 across languages, countries, genders, and sexual orientations., Results: The BEDS-7 demonstrated scalar factorial invariance across languages and countries, indicating consistent factor loadings and item intercepts. In contrast, the screener showed residual invariance across gender and sexual orientation groups, supporting its robustness across these demographics. Kruskal-Wallis tests revealed significant differences in BED symptoms across languages, countries, genders, and sexual orientations, with the highest BED scores observed among queer, pansexual, and gender-diverse individuals. The BEDS-7 also demonstrated adequate reliability (Cronbach's alpha > 0.80) and moderate criterion validity., Discussion: The findings provide further evidence of the reliability and validity of the BEDS-7 as a potential screening tool for identifying probable cases of BED globally, facilitating early intervention in primary care settings., (© 2025 The Author(s). International Journal of Eating Disorders published by Wiley Periodicals LLC.)

The semienclosed Bouraké lagoon in New Caledonia is a natural system that enables observation of evolution in action with respect to stress tolerance in marine organisms, a topic directly relevant to understanding the consequences of global climate change. Corals inhabiting the Bouraké lagoon endure extreme conditions of elevated temperature (> 33°C), acidification (7.2 pH units), and deoxygenation (2.28 mg O2 L-1), which fluctuate with the tide due to the lagoon's geomorphology. To investigate the underlying bases of the apparent stress tolerance of these corals, we combined whole genome resequencing of the coral host and ITS2 metabarcoding of the photosymbionts from 90 Acropora tenuis colonies from three localities along the steep environmental gradient from Bouraké to two nearby control reefs. Our results highlight the importance of coral flexibility to associate with different photosymbionts in facilitating stress tolerance of the holobiont; but, perhaps more significantly, strong selective effects were detected at specific loci in the host genome. Fifty-seven genes contained SNPs highly associated with the extreme environment of Bouraké and were enriched in functions related to sphingolipid metabolism. Within these genes, the conserved sensor of noxious stimuli TRPA1 and the ABCC4 transporter stood out due to the high number of environmentally selected SNPs that they contained. Protein 3D structure predictions suggest that a single-point mutation causes the rotation of the main regulatory domain of TRPA1, which may be behind this case of natural selection through environmental filtering. While the corals of the Bouraké lagoon provide a striking example of rapid adaptation to extreme conditions, overall, our results highlight the need to preserve the current standing genetic variation of coral populations to safeguard their adaptive potential to ongoing rapid environmental change., (© 2025 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Objective: The main aim of this pilot study was to examine the impact of sexual activity on objective and subjective sleep parameters., Methods: A repeated-measures counterbalanced, cross-over design with three conditions - no sex, solo masturbation, and partnered sex was employed with cohabiting couples. In this pilot study 14 individuals participated in the study (7 females, 7 males; mean age 29.9 ± 3.4years). Sexual activities and sleep were monitored for 11 consecutive nights using a portable polysomnography system (DREEM3) and daily sex and sleep surveys., Statistical Analyses: Linear mixed models were employed to examine differences in sleep, readiness, and motivation following three conditions (i.e., no sex, solo masturbation, and partnered sex). Cohen's d effect sizes with 95% confidence limits were also calculated for pairwise comparisons between conditions with the effect of magnitude interpreted as follows: small= 0.2, medium 0.5, large 0.8, very large 1.0. Wilcoxon Signed-Rank tests were conducted to compare the sleep stage concordance between partners across conditions., Results: Participants attempted sleep considerably later following the solo masturbation and partnered sex conditions compared to the no sex condition (p = .004). Wake after sleep onset and sleep efficiency improved considerably following solo masturbation and partnered sex compared to no sex (p < .05). No differences were observed across conditions for subjective sleep (p > .05). Sleep stage concordance for rapid eye movement sleep was longer when participants slept together regardless of whether they engaged or did not engage in sexual activity (p < .05)., Conclusions: Engaging in sexual activity, whether solo masturbation or partnered, significantly enhanced objective sleep quality by reducing wakefulness after sleep onset and improving sleep efficiency. Objective wake up time, sleep duration, sleep latency and subjective sleep measures showed no differences postsexual activity, potentially attributable to the small sample size and the inclusion of only healthy sleepers. Future research should focus on expanding the sample size and incorporating participants with sleep disorders to thoroughly investigate if sexual activity before bedtime can improve sleep., Competing Interests: Declaration of conflicts of interest The authors report no declarations of interest. The authors alone are responsible for the content and writing of this article., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Athletes often experience poor sleep quality and quantity which may hinder physical performance and cognitive function. Presleep nutritional strategies may be an alternative to pharmacological interventions to improve sleep. The aim of this study was to examine the effect of two different doses of a nutritional intervention (both containing high Glycemic Index carbohydrate, whey, tryptophan, theanine, and 5'AMP) versus placebo on objective and subjective sleep, next-morning physical performance, cognitive function, and postural sway. Seventeen healthy, trained adult males completed three double-blind trials in a randomized, counterbalanced, crossover design. Participants were allocated to conditions using a Latin Square design. A (a) low-dose, (b) high-dose, or (c) placebo drink was provided 90 min before sleep each night. Polysomnography was used to measure objective sleep parameters. Cognitive function, postural sway, and subjective sleep quality were assessed 30 min after waking. Physical performance was assessed using a 10-min maximal effort cycling time trial each morning. All data were analyzed using linear mixed effects models and effect sizes were calculated using Cohen's d. This study was registered prospectively as a clinical trial with Australian New Zealand Clinical Trials Registry (registration number: NCT05032729). No significant main effects or improvements were observed in objective or subjective sleep parameters, physical performance, cognitive function, or postural sway. The low-dose intervention appeared to reduce N3 sleep duration compared with placebo (-13.6 min). The high-dose intervention appeared to increase N1 sleep duration compared with placebo (+7.4 min). However, the magnitude of changes observed were not likely to cause meaningful reductions in sleep quality and quantity.

Background and Aims: The Moral Incongruence Model of Pornography Use proposes that pornography-use-related problems may be present due to problematic pornography use (PPU) and/or moral disapproval (MD) of pornography use. Despite some supporting empirical evidence, no study has tested the presence of different pornography-use profiles based on individuals' behavioral dysregulation (i.e., PPU) and moral values concerning pornography use. The generalizability of previous findings to diverse populations has also been limited given the scarcity of studies conducted outside of Western countries., Methods: Using data from the International Sex Survey (42 countries, N = 66,994; Mage = 32.16 years, SD = 12.27), we conducted latent profile analysis to identify pornography-use profiles based on individuals' frequency of use, MD, and PPU. The profiles were compared along a wide range of pornography-use-related, sexuality-related, and psychological correlates., Results: Six pornography-use profiles were identified, including two increased risk groups (i.e., Increased risk of PPU without MD and Increased risk of PPU with some MD). Several factors differentiated between the increased risk vs. no/low risk profiles (e.g., relatedness satisfaction) as well as between the two increased risk profiles (e.g., religiosity). Apart from behavioral dysregulation, moral values concerning pornography use played an important role in distinguishing pornography-use profiles and demonstrated the importance of inquiring about MD when working with individuals with pornography-use-related problems., Conclusion: Findings also support recent calls for better-integrated sex therapy and sexual medicine perspectives into pornography-use-related problems research and care.

Background and Aims: Despite a growing body of research on pornography use among women, there is a lack of understanding of the problematic versus non-problematic nature. The current study aimed to investigate the relationship between women's motivations for pornography use and sexual wellbeing using a cross-sectional, self-report survey design among participants from 42 countries., Methods: The total sample included 82,243 participants, of whom 46,874 (57.0%) identified as women and were analyzed. The participants' age averaged at M = 29.67 years, with a standard deviation of SD = 10.11. Participants were asked to complete a questionnaire assessing their motivations for pornography use, as well as measures of sexual functioning, sexual desire, and sexual satisfaction., Results: Study results suggest that across cultures, women's motivations for pornography use are associated with their sexual wellbeing. Specifically, when women reported using pornography for their own pleasure or sexual curiosity, it was associated with fewer sexual functioning problems and higher sexual desire. Conversely, when women reported using pornography due to a lack of sexual satisfaction in their relationships, it was associated with more sexual functioning problems., Discussion and Conclusions: These findings highlight the need to consider the multifaceted nature of pornography use among women, including the usage motives, to fully understand associations with sexual wellbeing. Additionally, the study emphasizes the importance of conducting further research utilizing longitudinal designs, to establish the directionality between pornography use motivations and sexual wellbeing among women.

During transport through the oviduct, sperm interact with epithelial cells by attaching to specific glycans, a mechanism believed to select sperm and prolong their viability. An in vitro model of sperm-oviduct interactions was developed, consisting of a glass surface (either a slide or a coverslip) to which an oviduct glycan (sulfated Lewis X trisaccharide; suLe X ) is coupled. The ability of porcine sperm to attach to suLe X -surfaces and detach in response to progesterone and mature cumulus-oocyte complexes (COCs) was validated. The suLe X -coverslip was adapted for in vitro fertilization (IVF), termed glycan-IVF, by allowing porcine sperm to first bind suLe X before transferring mature COCs. The glycan-IVF method produced a percentage of fertilized oocytes comparable to that of conventional IVF (75.1 vs. 72.0%). Finally, the ability of the suLe X -coverslip to maintain sperm fertilizing ability over time was assessed. After 24 h of incubation, fertilization by sperm bound to the suLe X -coverslip was sustained, compared to sperm with unmodified coverslips (12.0 vs. 1.0%, p < 0.05). Furthermore, the percentage of polyspermic zygotes was reduced in the suLe X -coverslip method (17.7 vs. 41.3%, p < 0.05). This study validated an in vitro model for studying sperm-oviduct interactions, with potential applications in assisted reproductive technologies., Competing Interests: Declarations. Competing interests: S.S.-H. is currently employed by Epivara, Inc. L.V., N.B., and D.M. declare no competing interests., (© 2025. The Author(s).)

X-ray crystal diffraction has provided atomic-level structural information on biological macromolecules. Data quality determines the reliability of structural models. In most cases, multiple data sets are available from different crystals and/or collected with different experimental settings. Reliable metrics are critical to rank and select the data set with the highest quality. Many measures have been created or modified for data quality evaluation. However, some are duplicate in functionality, and some are likely misused due to misunderstanding, which causes confusion or problems, especially at synchrotron beamlines where experiments proceed quickly. In this work, these measures are studied through both theoretical analysis and experimental data with various characteristics, which demonstrated that: 1). {Rmerg, Rmeas, Rpim, CC1/2} all measure the equivalence of reflections, and the low-shell values of these metrics can be used as reliable indicators for correctness (or trueness) of Laue symmetry; 2). High-shell I / σ I is a reliable and better indicator to select resolution cutoff while the overall value measures the overall strength of the data.

COVID-19 safety required rapid transitions to online learning across education. This posed unique challenges for veterinary anatomy, which is a practical subject. This study compares the cognitive load and academic performance of first- and second-year veterinary students studying anatomy in 2019 (pre-COVID-19) and 2020 (post-COVID-19 teaching adjustments). Importantly, the core teaching content remained identical for both courses in 2019 and 2020 apart from teaching method (in-person vs. online), allowing us to isolate the effects of teaching method on cognitive load and academic performance. Cognitive load was measured among first- ( n 2019 = 105, n 2020 = 49) and second-year students ( n 2019 = 85, n 2020 = 42) at the end of each teaching semester, using a validated instrument. The instrument measures intrinsic load (IL, study material complexity), extraneous load (EL, presentation of material), and germane load (GL, self-perceived learning). t -Tests compared the 2019 and 2020 cohorts with respect to both cognitive load and academic performance. The results indicated that 2019 and 2020 cohorts did not differ on IL or EL in either the first- or second-year subject. However, among both first- and second-year students, the 2020 cohort reported significantly less GL compared to the 2019 cohort. Additionally, the first-year 2020 cohort performed at a significantly lower level than the first-year 2019 cohort. No significant difference in performances was reported between second-year cohorts. Therefore, despite being less inclined to perceive that online course activities enhanced their understanding of anatomy, second-year students with previous experience of learning anatomy in an in-person tertiary environment adjusted better than first-year students with limited experience.

To evaluate whether preoperative conversion from a gastrostomy tube (G-tube) to a gastrojejunostomy tube (GJ-tube) decreases short-term postoperative aspiration pneumonia and gastrointestinal complications in children with neuromuscular scoliosis. We conducted a retrospective chart review from January 2006 to October 2021 of pediatric patients who had neuromuscular scoliosis and were fed with a G-tube before spinal fusion. Eligible patients were divided into two groups based on whether they were converted to a GJ-tube preoperatively. Preoperative characteristics and 30-day postoperative outcomes were compared between groups using Chi-square tests. Of 261 eligible patients, 205 were converted to a GJ-tube, while 56 underwent spinal fusion with a G-tube. Common complications following G-tube to GJ-tube conversion were feeding intolerance (25.2%), GJ-tube malfunction (17.7%), and at least one episode of vomiting (17.4%). Within 30 days of discharge, 12.5% of GJ-tube patients and 11.5% of G-tube patients experienced aspiration pneumonia ( P  = 0.85). The GJ-tube group received postoperative tube feeds 7 hours earlier than the G-tube group on average (51.6 h vs. 44.5 h, P  = 0.02). Within 30 days of discharge, one (0.5%) patient from the GJ-tube group died of gastrointestinal complications unrelated to conversion and two (3.6%) patients in the G-tube group died from aspiration pneumonia ( P  = 0.12). Results suggest that there were no appreciable differences in outcomes between patients converted to a GJ-tube preoperatively compared to those who continued to use a G-tube. However, preoperative characteristics indicate that a higher number of complex patients were converted to a GJ-tube, indicating potential selection bias in this retrospective sample. Level of evidence: Level III., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules containing a ligand for a protein of interest linked to an E3 ubiquitin ligase ligand that induce protein degradation through E3 recruitment to the target protein. Small changes in PROTAC linkers can have drastic consequences, including loss of degradation activity, but the structural mechanisms governing such changes are unclear. To study this phenomenon, we screened PROTACs of diverse targeting modalities and identified dTAG-13 as an activator of the xenobiotic-sensing pregnane X receptor (PXR), which promiscuously binds various ligands. Characterization of dTAG-13 analogs and precursors revealed interplay between the PXR-binding moiety, linker, and E3 ligand that altered PXR activity without inducing degradation. A crystal structure of PXR ligand binding domain bound to a precursor ligand showed ligand-induced binding pocket distortions and a linker-punctured tunnel to the protein exterior at a region incompatible with E3 complex formation, highlighting the effects of linker environment on PROTAC activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The high-fidelity sesquiterpene cyclase (-)-germacradien-4-ol synthase (GdolS) converts farnesyl diphosphate into the macrocyclic alcohol (-)-germacradien-4-ol. Site-directed mutagenesis was used to decipher the role of key residues in the water control mechanism. Replacement of Ala176, located in the G1/2 helix, with non-polar aliphatic residues of increasing size (valine, leucine, isoleucine and methionine) resulted in the accumulation of the non-hydroxylated products germacrene A and germacrene D. In contrast, hydroxylation was maintained when the polar residues threonine, glutamine or aspartate replaced Ala176. Additionally, although a contribution of His150 to the nucleophilic water addition could be ruled out, the imidazole ring of His150 appears to assist carbocation stabilisation. The results presented here shed light on how hydroxylating sesquiterpene synthases can be engineered to design modified sesquiterpene synthases to reduce the need for further steps in the biocatalytic production of oxygenated sesquiterpenoids., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Sexual desire is a complex construct with important implications for sexual functioning and well-being. In this research, we translated the Sexual Desire Inventory (SDI-2), a widely used scale for assessing sexual (desire), into 25 languages from English and used data from the International Sex Survey (ISS) to (a) investigate its psychometric properties (i.e. factorial structure, reliability, validity, and measurement invariance) and (b) explore the expression of sexual desire across different countries, genders, and sexual orientations. A total of 82,243 participants from 42 countries completed the SDI-2, along with other sexuality-related scales. Confirmatory factor analysis supported a three-factor solution for the SDI-2 (CFI = .980; RMSEA = .060), encompassing the domains of "Partner-related," "Attractive-person-related," and "Solitary" sexual desire. The reliability of the total score and subscales were excellent. Likewise, correlations with other sexuality-related variables were positive yet weak-to-moderate in effect size. Measurement invariance tests supported its use across countries, languages, genders, and sexual orientations. Analysis of SDI-2 scores according to these variables supported its ability to capture group-based differences in sexual desire. In sum, the SDI-2 constitutes a psychometrically robust measure for the assessment of sexual desire in non-clinical samples with utility in large-scale cross-cultural studies.

Alcohol is commonly consumed prior to bedtime with the belief that it facilitates sleep. This systematic review and meta-analysis investigated the impact of alcohol on the characteristics of night-time sleep, with the intent to identify the influence of the dose and timing of alcohol intake. A systematic search of the literature identified 27 studies for inclusion in the analysis. Changes in sleep architecture were observed, including a delay in the onset of rapid eye movement (REM) sleep and a reduction in the duration of REM sleep. A dose-response relationship was identified such that disruptions to REM sleep occurred following consumption of a low dose of alcohol (≤0.50 g∙kg -1 or approximately two standard drinks) and progressively worsened with increasing doses of alcohol. Reductions in sleep onset latency and latency to deep sleep (i.e., non-rapid eye movement stage three (N3)) were only observed following the consumption of a high dose of alcohol (≥0.85∙g kg -1 or approximately five standard drinks). The effect of alcohol on the remaining characteristics of sleep could not be determined, with large uncertainty observed in the effect on total sleep time, sleep efficiency, and wake after sleep onset. The results of the present study suggest that a low dose of alcohol will negatively impact (i.e., reduce) REM sleep. It appears that high doses of alcohol may shorten sleep onset latency, however this likely exacerbates subsequent REM sleep disruption. Future work on personal and environmental factors that affect alcohol metabolism, and any differential effects of alcohol due to sex is encouraged., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Specificity of the ubiquitin-proteasome system depends on E3 ligase-substrate interactions. Many such pairings depend on E3 ligases binding to peptide-like sequences - termed N- or C-degrons - at the termini of substrates. However, our knowledge of structural features distinguishing closely related C-degron substrate-E3 pairings is limited. Here, by systematically comparing ubiquitylation activities towards a suite of common model substrates, and defining interactions by biochemistry, crystallography, and cryo-EM, we reveal principles of C-degron recognition across the KLHDCX family of Cullin-RING ligases (CRLs). First, a motif common across these E3 ligases anchors a substrate's C-terminus. However, distinct locations of this C-terminus anchor motif in different blades of the KLHDC2, KLHDC3, and KLHDC10 β-propellers establishes distinct relative positioning and molecular environments for substrate C-termini. Second, our structural data show KLHDC3 has a pre-formed pocket establishing preference for an Arg or Gln preceding a C-terminal Gly, whereas conformational malleability contributes to KLHDC10's recognition of varying features adjacent to substrate C-termini. Finally, additional non-consensus interactions, mediated by C-degron binding grooves and/or by distal propeller surfaces and substrate globular domains, can substantially impact substrate binding and ubiquitylatability. Overall, the data reveal combinatorial mechanisms determining specificity and plasticity of substrate recognition by KLDCX-family C-degron E3 ligases., Competing Interests: Competing interests D.C.S. and B.A.S. are co-inventors of intellectual property that is unrelated to this work (DCN1 inhibitors licensed to Cinsano). J.W.H. is a founder and consultant for Caraway Therapeutics and is a scientific advisory board member for Lyterian Therapeutics. SJE is a founder of, and holds equity in TScan Therapeutics and Immune ID. S.J.E. is also founder of MAZE Therapeutics, and Mirimus and serves on the scientific advisory board of TSCAN Therapeutics, and MAZE Therapeutics. In accordance with Partners HealthCare’s conflict of interest policies, the Partners Office for Interactions with Industry has reviewed SJE’s financial interest in TSCAN and determined that it creates no significant risk to the welfare of participants in this study or to the integrity of this research. B.A.S. is a member of the scientific advisory boards of Biotheryx and Proxygen. The remaining authors declare no competing interests., (© 2024. The Author(s).)

The cerebral cortex comprises many distinct regions that differ in structure, function, and patterns of connectivity. Current approaches to parcellating these regions often take advantage of functional neuroimaging approaches that can identify regions involved in a particular process with reasonable spatial resolution. However, neuroanatomical biomarkers are also very useful in identifying distinct cortical regions either in addition to, or in place of functional measures. For example, differences in myelin density are thought to relate to functional differences between regions, are sensitive to individual patterns of experience, and have been shown to vary across functional hierarchies in a predictable manner. Accordingly, the current study provides quantitative stereological estimates of myelin density for each of the 13 regions that make up the feline auditory cortex. We demonstrate that significant differences can be observed between auditory cortical regions, with the highest myelin density observed in the regions that comprise the auditory core (i.e., the primary auditory cortex and anterior auditory field). Moreover, our myeloarchitectonic map suggests that myelin density varies in a hierarchical fashion that conforms to the traditional model of spatial organization in auditory cortex. Taken together, these results establish myelin as a useful biomarker for parcellating auditory cortical regions, and provide detailed estimates against which other, less invasive methods of quantifying cortical myelination may be compared., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most scientific facilities produce large amounts of heterogeneous data at a rapid pace. Managing users, instruments, reports and invoices presents additional challenges. To address these challenges, EMhub, a web platform designed to support the daily operations and record-keeping of a scientific facility, has been introduced. EMhub enables the easy management of user information, instruments, bookings and projects. The application was initially developed to meet the needs of a cryoEM facility, but its functionality and adaptability have proven to be broad enough to be extended to other data-generating centers. The expansion of EMHub is enabled by the modular nature of its core functionalities. The application allows external processes to be connected via a REST API, automating tasks such as folder creation, user and password generation, and the execution of real-time data-processing pipelines. EMhub has been used for several years at the Swedish National CryoEM Facility and has been installed in the CryoEM center at the Structural Biology Department at St. Jude Children's Research Hospital. A fully automated single-particle pipeline has been implemented for on-the-fly data processing and analysis. At St. Jude, the X-Ray Crystallography Center and the Single-Molecule Imaging Center have already expanded the platform to support their operational and data-management workflows., (open access.)

PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2. Ligands were identified that engage the C-degron binding site in KLHDC2, subjected to structure-based improvement, and linked to JQ1 for BET-family neo-substrate recruitment. Consideration of the exit vector emanating from the ligand engaged in KLHDC2's U-shaped degron-binding pocket enabled generation of SJ46421, which drives formation of a remarkably cooperative, paralog-selective ternary complex with BRD3 BD2 . Meanwhile, screening pro-drug variants enabled surmounting cell permeability limitations imposed by acidic moieties resembling the KLHDC2-binding C-degron. Selectivity for BRD3 compared to other BET-family members is further manifested in ubiquitylation in vitro, and prodrug version SJ46420-mediated degradation in cells. Selectivity is also achieved for the ubiquitin ligase, overcoming E3 auto-inhibition to engage KLHDC2, but not the related KLHDC1, KLHDC3, or KLHDC10 E3s. In sum, our study establishes neo-substrate-specific targeted protein degradation via KLHDC2, and provides a framework for developing selective PROTAC protein degraders employing C-degron E3 ligases., (© 2024. The Author(s).)

One of the practical contributions of epidemiology studies is to inform risk assessment and management to protect public health. However, there is a perception among some that environmental and occupational epidemiology is falling short of satisfying the needs of risk assessors. The specific reasons for this are not clearly understood. To help identify the points of dissatisfaction and possible areas for mutual learning, we conducted a survey of risk assessors, seeking their opinions of epidemiology research. We present a few quantitative measures and a thematic analysis of responses to open-ended questions. Survey results suggest that some risk assessors (with some adamant exceptions) believe that epidemiology has great potential to contribute to risk assessment but can be deficient in many ways. For example, respondents identified the lack of full disclosure of methods, deficiencies in exposure assessment, the absence of comprehensive uncertainty analyses, and the failure to investigate or explore thresholds of effects as some of the common shortcomings. These could be straightforward to address. Respondents also brought up a wide collection of more complicated and subtle concerns that could lead to further improvement of useful results. We identify areas where mutually-educating interdisciplinary dialogue seems particularly promising. Epidemiology research is expensive, and risk management decisions even more so; therefore, it is desirable for the risk assessment and epidemiologic communities to work toward making epidemiologic research more useful for informing decisions., Competing Interests: The authors declare no financial conflicts of interest other than their employment relationships with companies that might have some unidentified goals that conflict with the goals of this work. IB and CVP disclose activism on behalf of better bias analyses and other improvements in the conduct of epidemiology, belief in existence of thresholds in biology, and sincere desire to make risk assessment more quantitative. While there is no apparent way that the financing of this project would create any conflict of interest regarding the project goals, design, or analysis, we also disclose that CVP was contracted for this project by HESI, IB subsumed it into his academic duties, SD worked on it as part of her employment at HESI, and the other authors volunteered their time., (© 2024 The Authors.)

Background: The aim of this study was to examine the effect of pressure training on the performance of semi-professional female rugby league athletes., Methods: Using a within-subjects design, 16 female athletes (19.9 ± 3.4 years) performed a passing accuracy task under three conditions; (1) a control condition; (2) a physiological fatigue condition; and (3) a threat of consequence condition. Passing performance, perceived pressure, rate of perceived exertion (RPE), and self-confidence were assessed., Results: A significant main effect of conditions was found for rate of perceived exertion ( p < 0.001), self-confidence ( p < 0.028), and perceived pressure ( p = 0.011). There was no main effect of condition on passing performance. Post hoc comparisons revealed that RPE was significantly higher in the physiological fatigue condition when compared to the control ( p = 0.009) and threat of consequence conditions ( p < 0.001). Perceived pressure was significantly higher in the threat of consequence condition compared to the control condition ( p = 0.037)., Conclusions: The main findings of this study are that (1) passing performance was not impacted by pressure training conditions, and (2) threats of consequences are an effective manipulation to generate pressure in female semi-professional rugby league players. These results offer nuanced insights into the impact of pressure generation in training environments for female semi-professional rugby league athletes.

Purpose: To describe the incidence of reoperation and factors contributing to surgical revision within a minimum of 10 years after spinal fusion for scoliosis in patients with nonambulatory cerebral palsy (CP)., Methods: We conducted a retrospective review of consecutive nonambulatory patients with CP who underwent primary spinal fusion at a single specialty care center with a minimum of 10 years from their index surgery (surgery dates 2001-2011). Causes of reoperation were classified as implant failure/pseudoarthrosis, surgical site infection (SSI), proximal junctional kyphosis, prominent/symptomatic implants, and implant removal. Reoperation rates with 95% confidence intervals were calculated for each time interval, and an actuarial survival curve was generated., Results: 144 patients met inclusion criteria (mean age = 14.3 ± 2.6 years, 62.5% male); 85.4% had 5 years follow-up data; and 66.0% had 10 years follow-up data. Estimates from the actuarial analysis suggest that 14.9% (95% CI: 10.0-22.0) underwent reoperation by 5 years postsurgery, and 21.7% (95% CI: 15.4-30.1) underwent reoperation by 10 years postsurgery. The most common causes for reoperation were implant failure/pseudoarthrosis, SSI, and prominent/symptomatic implants., Conclusions: To our knowledge, this study is the largest long-term follow-up of nonambulatory patients with CP and neuromuscular scoliosis who underwent spinal fusion. Approximately 22% of these patients required reoperation 10 years after their index surgery, primarily due to implant failure/pseudoarthrosis, SSI, and prominent/symptomatic implants. Complications and reoperations continued throughout the 10 years period after index surgery, reinforcing the need for long-term follow-up as these patients transition into adulthood., Level of Evidence: III., (© 2024. The Author(s).)

Sponge microbiomes are often highly diverse making it difficult to determine which lineages are important for maintaining host health and homeostasis. Characterising genomic traits associated with symbiosis can improve our knowledge of which lineages have adapted to their host and what functions they might provide. Here we examined five microbial families associated with sponges that have previously shown evidence of cophylogeny, including Endozoicomonadaceae, Nitrosopumilaceae, Spirochaetaceae, Microtrichaceae and Thermoanaerobaculaceae, to better understand the mechanisms behind their symbiosis. We compared sponge-associated genomes to genomes found in other environments and found that sponge-specific clades were enriched in genes encoding many known mechanisms for symbiont survival, such as avoiding phagocytosis and defence against foreign genetic elements. We expand on previous knowledge to show that glycosyl hydrolases with sulfatases and sulfotransferases likely form multienzyme degradation pathways to break and remodel sulfated polysaccharides and reveal an enrichment in superoxide dismutase that may prevent damage from free oxygen radicals produced by the host. Finally, we identified novel traits in sponge-associated symbionts, such as urea metabolism in Spirochaetaceae which was previously shown to be rare in the phylum Spirochaetota. These results identify putative mechanisms by which symbionts have adapted to living in association with sponges., (© 2024 Commonwealth of Australia and The Author(s). Environmental Microbiology published by John Wiley & Sons Ltd.)

The future survival of coral reefs in the Anthropocene depends on the capacity of corals to adapt as oceans warm and extreme weather events become more frequent. Targeted interventions designed to assist evolutionary processes in corals require a comprehensive understanding of the distribution and structure of standing variation, however, efforts to map genomic variation in corals have so far focussed almost exclusively on SNPs, overlooking structural variants that have been shown to drive adaptive processes in other taxa. Here, we show that the reef-building coral, Acropora kenti, harbours at least five large, highly polymorphic structural variants, all of which exhibit signatures of strongly suppressed recombination in heterokaryotypes, a feature commonly associated with chromosomal inversions. Based on their high minor allele frequency, uniform distribution across habitats and elevated genetic load, we propose that these inversions in A. kenti are likely to be under balancing selection. An excess of SNPs with high impact on protein-coding genes within these loci elevates their importance both as potential targets for adaptive selection and as contributors to genetic decline if coral populations become fragmented or inbred in future., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

The UPPS-P Impulsive Behavior Model and the various psychometric instruments developed and validated based on this model are well established in clinical and research settings. However, evidence regarding the psychometric validity, reliability, and equivalence across multiple countries of residence, languages, or gender identities, including gender-diverse individuals, is lacking to date. Using data from the International Sex Survey ( N  = 82,243), confirmatory factor analyses and measurement invariance analyses were performed on the preestablished five-factor structure of the 20-item short version of the UPPS-P Impulsive Behavior Scale to examine whether (a) psychometric validity and reliability and (b) psychometric equivalence hold across 34 country-of-residence-related, 22 language-related, and three gender-identity-related groups. The results of the present study extend the latter psychometric instrument's well-established relevance to 26 countries, 13 languages, and three gender identities. Most notably, psychometric validity and reliability were evidenced across nine novel translations included in the present study (i.e., Croatian, English, German, Hebrew, Korean, Macedonian, Polish, Portuguese-Portugal, and Spanish-Latin American) and psychometric equivalence was evidenced across all three gender identities included in the present study (i.e., women, men, and gender-diverse individuals)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare no conflict of interest with respect to the content of this manuscript. Shane W. Kraus discloses that he has received funding from the International Center for Responsible Gaming, MGM Resorts International, Center for the Application of Substance Abuse Technologies, Taylor Francis, Springer Nature, The Nevada Problem Gambling Project, Sports Betting Alliance, and Kindbridge Research Institute. Marc N. Potenza discloses that he has consulted for and advised Game Day Data, Addiction Policy Forum, AXA, Idorsia, Baria-Tek, and Opiant Therapeutics; been involved in a patent application involving Novartis and Yale; received research support from the Mohegan Sun Casino and the Connecticut Council on Problem Gambling; consulted for or advised legal and gambling entities on issues related to impulse control and addictive behaviors; provided clinical care related to impulse-control and addictive behaviors; performed grant reviews; edited journals/journal sections; given academic lectures in grand rounds, CME events and other clinical/scientific venues; and generated books or chapters for publishers of mental health texts. The University of Gibraltar receives funding from the Gibraltar Gambling Care Foundation, an independent not-for-profit charity. The ELTE Eötvös Loránd University receives funding from Szerencsejáték Ltd. (the gambling operator of the Hungarian government) to maintain a telephone helpline service for problematic gambling. Julius Burkauskas discloses that he works as a consultant at Cronos. Roman Gabrhelík discloses that he is the shareholder of Adiquit Ltd., which is currently developing apps for addiction recovery. Vesta Steibliene discloses that she has received funding from the Lithuanian Health Promotion Fund for providing educational materials and lectures on problematic internet use.

A dynamic mucous layer containing numerous micro-organisms covers the surface of corals and has multiple functions including both removal of sediment and "food gathering." 1 It is likely to also act as the primary barrier to infection; various proteins and compounds with antimicrobial activity have been identified in coral mucus, though these are thought to be largely or exclusively of microbial origin. As in Hydra, 2 anti-microbial peptides (AMPs) are likely to play major roles in regulating the microbiomes of corals. 3 , 4 Some eukaryotes employ a complementary but less obvious approach to manipulate their associated microbiome by interfering with quorum signaling, effectively preventing bacteria from coordinating gene expression across a population. Our investigation of immunity in the reef-building coral Acropora millepora, 5 however, led to the discovery of a coral gene referred to here as AmNtNH1 that can inactivate a range of acyl homoserine lactones (AHLs), common bacterial quorum signaling molecules, and is induced on immune challenge of adult corals and expressed during the larval settlement process. Closely related proteins are widely distributed within the Scleractinia (hard corals) and some other cnidarians, with multiple paralogs in Acropora, but their closest relatives are bacterial, implying that these are products of one or more lateral gene transfer events post-dating the cnidarian-bilaterian divergence. The deployment by corals of genes used by bacteria to compete with other bacteria reflects a mechanism of microbiome manipulation previously unknown in Metazoa but that may apply more generally., Competing Interests: Declaration of interests The authors declare no completing interests., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Engineering sesquiterpene synthases to form predefined alternative products is a major challenge due to their diversity in cyclization mechanisms and our limited understanding of how amino acid changes affect the steering of these mechanisms. Here, we use a combination of atomistic simulation and site-directed mutagenesis to engineer a selina-4(15),7(11)-diene synthase (SdS) such that its final reactive carbocation is quenched by trapped active site water, resulting in the formation of a complex hydroxylated sesquiterpene (selin-7(11)-en-4-ol). Initially, the SdS G305E variant produced 20% selin-7(11)-en-4-ol. As suggested by modeling of the enzyme-carbocation complex, selin-7(11)-en-4-ol production could be further improved by varying the pH, resulting in selin-7(11)-en-4-ol becoming the major product (48%) at pH 6.0. We incorporated the SdS G305E variant along with genes from the mevalonate pathway into bacterial BL21(DE3) cells and demonstrated the production of selin-7(11)-en-4-ol at a scale of 10 mg/L in batch fermentation. These results highlight opportunities for the simulation-guided engineering of terpene synthases to produce predefined complex hydroxylated sesquiterpenes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

No reference intervals for serum biochemistry and haematology of sea turtles in Thailand exists to assist veterinarians who are responsible for sea turtle health management and treatment. This study determined serum biochemistry and basic haematology of healthy juvenile green sea turtles (n = 92) in captivity in Thailand following the American Society for Veterinary Clinical Pathology (ASVCP), Quality Assurance and Laboratory Standards Committee (QALS) guidelines for the determination of reference intervals in veterinary species. Biochemistry tests, including blood urea nitrogen, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were analysed using an IDEXX VetTest Chemistry Analyzer. Haematology parameters were measured manually using a microhaematocrit for packed cell volume (PCV), Neubauer counting chamber for red blood cell count and cyanmethemoglobin method for haemoglobin concentration. mean corpuscular volume and mean corpuscular haemoglobin concentration were calculated using the PCV, red blood cell count and haemoglobin. Turtles in this study were found to have higher mean values for PCV (28.70%), haemoglobin (92.13 g/L), mean corpuscular haemoglobin concentration (327.03 g/L), uric acid (247.15 μmol/L), alanine aminotransferase (16.53 IU/L), aspartate aminotransferase (209.44 IU/L), and alkaline phosphatase (245.08 IU/L) compared to sea turtles in Brazil. The reference intervals established using high numbers of healthy turtles in this study will assist veterinarians with diagnostic and treatment decisions when evaluating laboratory results for juvenile green sea turtles., (© 2024 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Background: The brain is built of neurons supported by myelin, a fatty substance that improves cellular communication. Noninvasive magnetic resonance imaging (MRI) is now able to measure brain structure like myelin and requires histological validation., New Method: Here we present work in small and large biomedical model mammals to standardize a silver impregnation method as a high-throughput histological myelin visualization procedure. Specifically, we built a new staining well plate to increase batch size, and then systematically varied the staining and clearing cycles to describe the staining response curve across taxa and conditions. We compared tissues fixed by immersion or perfusion, mounted versus free-floating, and cut as thicker or thinner slices, with two-weeks of post-fixation., Results: The staining response curves show optimal staining with a single exposure across taxa when incubation and clearing epochs are held to within 3-9 min. We show that clearing was slower in mounted vs free-floating tissue, and that staining was faster and caused fracturing earlier in thinner sliced and smaller volumes of tissue., Comparison With Existing Methods: We developed a batch processing approach to increase throughput while ensuring reproducibility and demonstrate the optimal conditions for fine myelinated fiber morphology visualization with short cycles (<9 minutes)., Conclusions: We present our optimized protocol to reveal mesoscale neuroanatomical myelin content in histology across mammals. This standard staining procedure will facilitate multiscale analyses of myelin content across development as well as in the presence of injury or disease., Competing Interests: Declaration of Competing Interest We declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Motivations for pornography use may vary across gender identities, sexual orientations, and geographical regions, warranting examination to promote individual and public health. The aims of this study were to validate the Pornography Use Motivations Scale (PUMS) in a diverse, multicultural sample, and develop a short form (PUMS-8) that can assess a wide range of pornography use motivations. Using data from 42 countries ( N  = 75,117; M age  = 32.07; SD age  = 12.37), enabled us to thoroughly evaluate the dimensionality, validity, and reliability of the Pornography Use Motivations Scale (PUMS), leading to the development of the more concise PUMS-8 short scale. Additionally, language-, nationality-, gender-, and sexual-orientation-based measurement invariance tests were conducted to test the comparability across groups. Both the PUMS and the PUMS-8 assess eight pornography use motivations, and both demonstrated excellent psychometric properties. Sexual Pleasure emerged as the most frequent motivation for pornography use across countries, genders, and sexual orientations, while differences were observed concerning other motivations (e.g. self-exploration was more prevalent among gender-diverse individuals than men or women). The motivational background of pornography use showed high similarity in the examined countries. Both the PUMS and the PUMS-8 are reliable and valid measurement tools to assess different types of motivations for pornography use across countries, genders, and sexual orientations. Both scales are recommended for use in research and clinical settings.

Background: Photobiomodulation therapy (PBMT) using devices to deliver red and/or near-infrared light to tissues has shown promising effects in clinical settings for respiratory diseases, including potential benefits in managing symptoms associated with COVID-19. Objective: To determine if at-home self-administered PBMT for patients with COVID-19 is safe and effective. Methods: This was a randomized controlled trial (RCT) carried out at home during the COVID-19 pandemic (September 2020 to August 2021). The treatment group self-administered the Vielight RX Plus PBMT device (635 nm intranasal and 810 nm chest LEDs) and were monitored remotely. Eligible patients scored 4-7 (out of 7) for severity on the Wisconsin Upper Respiratory Symptom Survey (WURSS-44). Patients were randomized equally to Control group receiving standard-of-care (SOC) only or Treatment group receiving SOC plus PBMT. The device was used for 20 min 2X/day for 5 days and, subsequently, once daily for 30 days. The primary end-point was time-to-recovery (days) based on WURSS-44 question 1, "How sick do you feel today?". Subgroup analysis was performed, and Kaplan-Meier and Cox Proportional Hazards analysis were employed. Results: One hundred and ninety-nine eligible patients (18-65 years old) were divided into two subgroups as follows: 136 patients with 0-7 days of symptoms at baseline and 63 patients with 8-12 days of symptoms. Those with 0-7 days of symptoms at baseline recovered significantly faster with PBMT. The median for Treatment group was 18 days [95% confidence interval (CI), 13-20] versus the Control group 21 days (95% CI, 15-28), p = 0.050. The treatment:control hazard ratio was 1.495 (95% CI, 0.996-2.243), p = 0.054. Patients with symptom duration ≥7 days did not show any significant improvement. No deaths or severe adverse events (SAEs) occurred in the Treatment group, whereas there was 1 death and 3 SAEs requiring hospitalization in the Control group. Conclusions: Patients with ≤7 days of COVID-19 symptoms recovered significantly faster with PBMT compared to SOC. Beyond 7 days, PBMT showed no superiority over SOC. Trial Registration: ClinicalTrials.gov NCT04418505.

Nuclear receptors are ligand-activated transcription factors that can often be useful drug targets. Unfortunately, ligand promiscuity leads to two-thirds of receptors remaining clinically untargeted. PXR is a nuclear receptor that can be activated by diverse compounds to elevate metabolism, negatively impacting drug efficacy and safety. This presents a barrier to drug development because compounds designed to target other proteins must avoid PXR activation while retaining potency for the desired target. This problem could be avoided by using PXR antagonists, but these compounds are rare, and their molecular mechanisms remain unknown. Here, we report structurally related PXR-selective agonists and antagonists and their corresponding co-crystal structures to describe mechanisms of antagonism and selectivity. Structural and computational approaches show that antagonists induce PXR conformational changes incompatible with transcriptional coactivator recruitment. These results guide the design of compounds with predictable agonist/antagonist activities and bolster efforts to generate antagonists to prevent PXR activation interfering with other drugs., (© 2024. The Author(s).)

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets., (© 2024. Argonne National Laboratory, Battelle Memorial Institute, UT- Battelle, LLC, Brookhaven National Laboratory, National Renewable Energy Laboratory, AMES National Laboratory, Lawrence Berkley National Laboratory, SLAC National Accelerator Laboratory, Booz Allen Hamilton, BASF Corporation and The Author(s), under exclusive licence to Springer Nature Limited. This work contains contributions, authored by US Government employees in the course of their official duties, which are not subject to copyright protection in the US. Foreign copyright protection for these contributions may still apply.)

Background: Sleep is a critical component of recovery, but it can be disrupted following prolonged endurance exercise. The objective of this study was to examine the capacity of male and female professional cyclists to recover between daily race stages while competing in the 2022 Tour de France and the 2022 Tour de France Femmes, respectively. The 17 participating cyclists (8 males from a single team and 9 females from two teams) wore a fitness tracker (WHOOP 4.0) to capture recovery metrics related to night-time sleep and autonomic activity for the entirety of the events and for 7 days of baseline before the events. The primary analyses tested for a main effect of 'stage classification'-i.e., rest, flat, hilly, mountain or time trial for males and flat, hilly or mountain for females-on the various recovery metrics., Results: During baseline, total sleep time was 7.2 ± 0.3 h for male cyclists (mean ± 95% confidence interval) and 7.7 ± 0.3 h for female cyclists, sleep efficiency was 87.0 ± 4.4% for males and 88.8 ± 2.6% for females, resting HR was 41.8 ± 4.5 beats·min -1 for males and 45.8 ± 4.9 beats·min -1 for females, and heart rate variability during sleep was 108.5 ± 17.0 ms for males and 119.8 ± 26.4 ms for females. During their respective events, total sleep time was 7.2 ± 0.1 h for males and 7.5 ± 0.3 h for females, sleep efficiency was 86.4 ± 1.2% for males and 89.6 ± 1.2% for females, resting HR was 44.5 ± 1.2 beats·min -1 for males and 50.2 ± 2.0 beats·min -1 for females, and heart rate variability during sleep was 99.1 ± 4.2 ms for males and 114.3 ± 11.2 ms for females. For male cyclists, there was a main effect of 'stage classification' on recovery, such that heart rate variability during sleep was lowest after mountain stages. For female cyclists, there was a main effect of 'stage classification' on recovery, such that the percentage of light sleep (i.e., lower-quality sleep) was highest after mountain stages., Conclusions: Some aspects of recovery were compromised after the most demanding days of racing, i.e., mountain stages. Overall however, the cyclists obtained a reasonable amount of good-quality sleep while competing in these physiologically demanding endurance events. This study demonstrates that it is now feasible to assess recovery in professional athletes during multiple-day endurance events using validated fitness trackers., (© 2024. The Author(s).)

Background: University non-continuation, also termed as university dropout in literature, is a concern for institutions. Elevated stress levels, mental distress, and psychiatric issues affect academic performance and thus may contribute to non-continuation. There is a lack of systematic reviews exploring the link between mental health and university non-continuation., Aim: This systematic review aims to bridge this gap, by investigating the prevalence of non-continuation and mental health conditions among university students, and the impact of mental health on university non-continuation., Methods: Following PRISMA guidelines this review synthesized data from 67 studies, utilising both narrative synthesis and meta-analytic techniques., Results: The results revealed that the included studies reported a range of university non-continuation rates (5.9% to 43.6%) with a pooled prevalence of 17.9%, 95% CI [14.2%, 22.3%]. The prevalence of mental health concerns among students varied widely (2.2% to 83.6%), with a pooled prevalence of 26.3%, 95% CI [16.0%, 40.0%]. Depression, OR = 1.143 (95% CI [1.086, 1.203] p<.001), stress, OR = 1.413 (95% CI [1.106, 1.805], p=.006), and other mental health conditions, OR = 1.266 (95% CI [1.133, 1.414], p <.001), were associated with higher non-continuation., Conclusion: Some mental health conditions elevate non-continuation risks, and addressing mental health may enhance student retention in higher education.