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Simulating electrolyte–electrode systems poses challenges due to the need to account for the electrode's response to ion movements in order to maintain a constant electrode potential, which slows down the simulations. To circumvent this, computationally more efficient constant charge (CC) simulations are sometimes employed. However, the accuracy of CC simulations in capturing the behavior of electrolyte–electrode systems remains unclear, especially for microporous electrodes. Herein, we consider electrolyte-filled slit nanopores and systematically analyze the in-pore ion structure and diffusivity using CC and constant potential simulations. Our results indicate that CC simulations provide comparable pore occupancies at high bulk ion densities and for highly charged pores, but they fail to accurately describe the ion structure and dynamics, particularly in quasi-2D (single-layer) pores and at low ion densities. We attribute these results to the superionic state emerging in conducting nanoconfinement and its interplay with excluded volume interactions. [ABSTRACT FROM AUTHOR]

Microgels exhibit the ability to undergo reversible swelling in response to shifts in environmental factors that include variations in temperature, concentration, and pH. While several models have been put forward to elucidate specific aspects of microgel swelling and its impact on bulk behavior, a consistent theoretical description that chains throughout the microscopic degrees of freedom with suspension properties and deepens into the full implications of swelling remains a challenge yet to be met. In this work, we extend the mean-field swelling model of microgels from Denton and Tang [J. Chem. Phys. 145, 164901 (2016)] to include the finite extensibility of the polymer chains. The elastic contribution to swelling in the original work is formulated for Gaussian chains. By using the Langevin chain model, we modify this elastic contribution in order to account for finite extensibility effects, which become prominent for microgels containing highly charged polyelectrolytes and short polymer chains. We assess the performance of both elastic models, namely for Gaussian and Langevin chains, comparing against coarse-grained bead–spring simulations of ionic microgels with explicit electrostatic interactions. We examine the applicability scope of the models under a variation of parameters, such as ionization degree, microgel concentration, and salt concentration. The models are also tested against experimental results. This work broadens the applicability of the microgel swelling model toward a more realistic description, which brings advantages when describing the suspensions of nanogels and weak-polyelectrolyte micro-/nanogels. [ABSTRACT FROM AUTHOR]

Mindfulness training programs have been a rapidly emerging form of managerial intervention and have stimulated debate over the individual and collective potentials of "new age" and humanistic management training. Such programs have been critiqued as individualistic, overly performance oriented, or deviating from collective wisdom traditions at their source. Yet we know little empirically about how actors in mindfulness programs experience the collectivity of mindfulness practices. Through a case study of a corporate mindfulness program, we examine how individual and collective elements of mindfulness are socially constructed by trainers, managers, and participants. We describe discourses of individual benefit, relationality, and macro-social aspirations, and how actors have attempted to link these different levels. By repositioning mindfulness as discursive and situated in ongoing practices, we propose a critical yet empirically situated research agenda around mindfulness interventions in organizational settings, with implications for humanistic and new age managerial education more generally. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide pivotal in migraine pathophysiology and is considered a promising new migraine drug target. Although intravenous PACAP triggers migraine attacks and a recent phase II trial with a PACAP-inhibiting antibody showed efficacy in migraine prevention, targeting the PACAP receptor PAC1 alone has been unsuccessful. The present study investigated the role of three PACAP receptors (PAC1, VPAC1 and VPAC2) in inducing migraine-relevant hypersensitivity in mice. Methods: Hindpaw hypersensitivity was induced by repeated PACAP38 injections. Tactile sensitivity responses were quantified using von Frey filaments in three knockout (KO) mouse strains, each lacking one of the PACAP-receptors (Ntotal = 160). Additionally, ex vivo wire myography was used to assess vasoactivity of the carotid artery, and gene expression of PACAP receptors was examined by qPCR. Results: PACAP38 induced hypersensitivity in WT controls (p < 0.01) that was diminished in VPAC1 and VPAC2 KO mice (p < 0.05). In contrast, PAC1 KO mice showed similar responses to WT controls (p > 0.05). Myograph experiments supported these findings showing diminished vasoactivity in VPAC1 and VPAC2 KO mice. We found no upregulation of the non-modified PACAP receptors in KO mice. Conclusions: This study assessed all three PACAP receptors in a migraine mouse model and suggests a significant role of VPAC receptors in migraine pathophysiology. The lack of hypersensitivity reduction in PAC1 KO mice suggests the involvement of other PACAP receptors or compensatory mechanisms. The results indicate that targeting only individual PACAP receptors may not be an effective migraine treatment. [ABSTRACT FROM AUTHOR]

Context Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion. Objective To examine whether fasting and stimulated glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW). Methods 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n = 22), OIS (n = 22), and NW (n = 36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated. Results Fasting concentrations of glucagon and GLP-1 were higher in the OIR group, with no significant differences for GIP. The OIR group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences in GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI. Conclusion Children and adolescents with OIR have elevated fasting concentrations of glucagon and GLP-1, higher glucagon and lower GLP-1 responses during an OGTT compared to those with OIS and NW. In contrast, individuals with OIS have similar hormone responses to those with NW. [ABSTRACT FROM AUTHOR]

Introduction: The present study aims to evaluate the role of sense of coherence and self-efficacy in relation to mental health and well-being, with and without social restrictions due to the COVID-19 pandemic. Additionally, this study seeks to investigate the differences in sense of coherence, self-efficacy, mental health and well-being depending on the manner in which the pandemic is being handled. Methods: A total of 27,162 students at Heidelberg University were surveyed via email at two measurement points, once with and once without social restrictions. The survey assessed sense of coherence, self-efficacy, mental health and well-being. To this end, the questionnaires Sense of Coherence Scale, Patient Health Questionnaire, WHO-Well-being-Index and the General Self-Efficacy Scale were employed. A total of 2,398 individuals participated in the initial measurement, while 701 individuals participated in the subsequent measurement. Results: The lifting of social restrictions has been associated with a notable improvement in well-being and mental health, particularly in the context of depressive syndromes. Further analysis demonstrated a positive correlation between the sense of coherence and self-efficacy at both measurement points, as well as between these two constructs and mental health and well-being. Furthermore, the sense of coherence and self-efficacy were found to account for a notable proportion of the observed variability in mental health and well-being values. Self-efficacy exhibited a significantly higher mean value at the initial measurement time point compared to the subsequent time point. In contrast, no significant difference was observed in the sense of coherence between the two measurement points. Discussion: The findings presented here illustrate the significance of social interaction, sense of coherence and self-efficacy for mental health and well-being. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are often accompanied by neuroinflammation and impairment of the blood-brain barrier (BBB) mediated by activated glial cells through their release of proinflammatory molecules. To study the effects of glial cells on mouse brain endothelial cells (mBECs), we developed an in vitro BBB model with inflammation by preactivating mixed glial cells (MGCs) with lipopolysaccharide (LPS) before co-culturing with mBECs to study the influence of molecules released by activated MGCs. The response of the mBECs to activated MGCs was compared to direct stimulation with LPS. The cytokine profile of activated MGCs was analyzed together with their effects on the mBEC's integrity, expression of tight junction proteins, adhesion molecules, and BBB-specific transport proteins. Stimulation of MGCs significantly upregulated mRNA expression and secretion of several pro-inflammatory cytokines. Co-culturing mBECs with pre-stimulated MGCs significantly affected the barrier integrity of mBECs similar to direct stimulation with LPS. The gene expression levels of tight junction proteins were unaltered, but tight junction proteins revealed rearrangements with respect to subcellular distribution. Compared to direct stimulation with LPS, the expression of cell-adhesion molecules was significantly increased when mBECs were co-cultured with prestimulated MGCs and thus pre-activating MGCs transforms mBECs into a proinflammatory phenotype. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to assess the clinical utility, safety, and tolerability in epilepsy patients of ultra long‐term monitoring with a novel subcutaneous electroencephalographic (EEG) device (sqEEG). Methods: Five patients with drug‐resistant focal epilepsy were implanted (one patient bilaterally) with sqEEG. In phase 1, we assessed sqEEG sensitivity for seizure recording by recording seizures simultaneously with scalp EEG in the epilepsy monitoring unit (EMU). sqEEG was scored either visually (v‐sqEEG) or by using a semiautomatic algorithm (EpiSight; E‐sqEEG). In phase 2, the patients were monitored as outpatients for 3–6 months. sqEEG data were analyzed monthly, evaluating concordance of data obtained by v‐sqEEG, E‐sqEEG, and patients' diaries. v‐sqEEG data were used to guide treatment adjustments. sqEEG‐related side effects were assessed throughout the study. Results: In phase 1, v‐sqEEG detected all seizures recorded in the EMU in all patients, whereas E‐sqEEG was as effective in three patients. In the other two patients, E‐sqEEG detected only a proportion or none of the seizures, respectively. Sensitivity of E‐sqEEG depended on the ictal EEG features. In phase 2, a 100% concordance between E‐sqEEG and v‐sqEEG in seizure detection was observed for the same three patients as in phase 1. In the other two patients (one implanted bilaterally), effectiveness of E‐sqEEG in detecting seizure as compared to v‐sqEEG ranged from 0% to 83%. v‐sqEEG showed that all patients reported in their diaries fewer seizures than they actually suffered. In four of five patients, v‐sqEEG showed that the treatment adjustments had been ineffective or associated with a seizure increment. The only side effect was an infection at the implantation site in one patient. Significance: The sqEEG system could collect reliable information on seizure activity, thus providing clinically relevant information. Sensitivity of EpiSight in detecting seizures varied across patients, depending on the ictal EEG features. sqEEG ultra long‐term monitoring was feasible and well tolerated. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVM) are benign vascular anomalies prone to pain, bleeding, and progressive growth. AVM are mainly caused by mosaic pathogenic variants of the RAS-MAPK pathway. However, a causative variant is not identified in all patients. Using ultra-deep sequencing, we identified novel somatic RIT1 delins variants in lesional tissue of three AVM patients. RIT1 encodes a RAS-like protein that can modulate RAS-MAPK signaling. We expressed RIT1 variants in HEK293T cells, which led to a strong increase in ERK1/2 phosphorylation. Endothelial-specific mosaic overexpression of RIT1 delins in zebrafish embryos induced AVM formation, highlighting their functional importance in vascular development. Both ERK1/2 hyperactivation in vitro and AVM formation in vivo could be suppressed by pharmacological MEK inhibition. Treatment with the MEK inhibitor trametinib led to a significant decrease in bleeding episodes and AVM size in one patient. Our findings implicate RIT1 in AVM formation and provide a rationale for clinical trials with targeted treatments. [ABSTRACT FROM AUTHOR]

Background: Predicting mortality in emergency departments (EDs) using machine learning models presents challenges, particularly in balancing simplicity with performance. This study aims to develop models that are both simple and effective for predicting short- and long-term mortality in ED patients. Our approach uses a minimal set of variables derived from one single blood sample obtained at admission. Methods: Data from three cohorts at two large Danish university hospitals were analyzed, including one retrospective and two prospective cohorts where prognostic models were applied to predict individual mortality risk, spanning the years 2013–2022. Routine biochemistry analyzed in blood samples collected at admission was the primary data source for the prediction models. The outcomes were mortality at 10, 30, 90, and 365 days after admission to the ED. The models were developed using Light Gradient Boosting Machines. The evaluation of mortality predictions involved metrics such as Area Under the Receiver Operating Characteristic Curve (AUC), sensitivity, specificity, negative predictive values, positive predictive values, and Matthews correlation coefficient (MCC). Results: A total of 43,648 unique patients with 65,484 admissions were analyzed. The models showed high accuracy, with very good to excellent AUC values between 0.87 and 0.93 across different time intervals. Conclusions: This study demonstrates that a single assessment of routine clinical biochemistry upon admission can serve as a powerful predictor for both short-term and long-term mortality in ED admissions. [ABSTRACT FROM AUTHOR]

Background: Coronary tortuosity (CorT) is frequently observed in invasive angiography, though its aetiology and clinical significance remain ambiguous. Prior research has indicated possible links between CorT and factors such as hypertension, age, and calcium scores in the left anterior descending (LAD) artery. The aim of this study was to examine and optimize the usage of coronary computed tomography angiography (CCTA) with vessel tracking to explore these associations. Methods: Observational sub‐study of the single centre randomised controlled CATCH‐trial. From the original study 600 participants, who underwent CCTA, 250 were randomly selected. Clinical data and patient risk factors were sourced from medical records and structured interviews. Tortuosity of the LAD was quantified by calculating the ratio of the actual vessel‐length to the straight‐line distance. Results: The final study population comprised 194 patients (56 patients were excluded due to poor image quality or inability to perform adequate vessel tracking). After adjusting for confounding variables, tortuosity was significantly associated with hypertension (p < 0.001), female gender (p = 0.01), and increasing age (p = 0.045). No significant correlation was observed between CorT and calcium scores. Univariate analysis indicated that higher CorT levels were linked to lower metabolic equivalents of task (METs) in bicycle tests (p = 0.003); however, this relationship became nonsignificant (p = 0.97) upon adjustment for age, gender, and hypertension. Conclusions: Our findings suggest that increased CorT is most prevalent in patients with hypertension, advancing age, and female gender. Although higher tortuosity levels did not significantly impact METs during physical activity, further research is warranted to explore the underlying mechanisms of this relationship. [ABSTRACT FROM AUTHOR]

Summary: Anti‐obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long‐term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs. These barriers can delay the AOM development and evaluation process, increase the cost of performing trials, create challenges in the interpretation of results, influence the generalizability of the findings and present ethical dilemmas. In an effort to address these issues and provide guidance to streamline the process of designing and conducting pediatric AOM clinical trials, relevant key stakeholders convened a series of roundtable meetings to discuss, debate and achieve harmonization on design features. Stakeholder participants included a multidisciplinary group of international pediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry. Topics of discussion included primary efficacy end‐points, secondary end‐points, eligibility criteria, trial run‐in and follow‐up phases, use of active comparators and guidelines for down‐titration and/or stopping rules for excessive weight reduction. Consensus recommendations were agreed upon. Regarding end‐points, emphasis was placed on moving away from BMI z‐score as a primary outcome, incorporating multiple alternative BMI‐related outcomes and measuring adiposity/body fat as a prominent secondary end‐point. Trial eligibility criteria were carefully considered to maximize generalizability while maintaining safety. The limited value of trial run‐in phases was discussed. It was also underscored that designing trials with extended follow‐up periods after AOM withdrawal should be avoided owing to ethical issues (including possible psychological harm) related to weight regain without providing the opportunity to access other treatments. The panel emphasized the value of the randomized, placebo‐controlled trial but recommended the thoughtful consideration of the use of active comparators in addition to, or instead of, placebo to achieve clinical equipoise when appropriate. Finally, the panel recommended that clinical trial protocols should include clear guidance regarding AOM down‐titration to avoid excessive weight reduction when applicable. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles? SUMMARY ANSWER Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1) levels as well as uterine volume in their daughters 16 years later. WHAT IS KNOWN ALREADY Endocrine-disrupting environmental chemicals may adversely affect human reproductive health, and many societies have experienced a trend toward earlier puberty and an increasing prevalence of infertility in young couples. The scientific evidence of adverse effects of foetal exposure to a large range of chemicals, including phthalates, on male reproductive health is growing, but very few studies have explored effects on female reproduction. STUDY DESIGN, SIZE, DURATION This follow-up study included 317 teenage daughters who were part of the Copenhagen Mother–Child Cohort, a population-based longitudinal birth cohort of 1210 females born between 1997 and 2002. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 317 female participants (median age 16 years) were examined for weight, height, and menstrual pattern. A serum sample was analysed for concentrations of reproductive hormones, and trans-abdominal 3D ultrasonography was performed to obtain the number of ovarian follicles, ovarian and uterine size. Prenatal maternal serum samples were available for 115 females, and cord blood samples were available for 118 females. These were analysed for concentrations of 32 phthalate metabolites. Weighted quantile sum regression was used for modelling associations of combined prenatal phthalate exposure with the reproductive outcomes in post-menarcheal females. MAIN RESULTS AND THE ROLE OF CHANCE In bivariate correlation analyses, negative significant associations were found between several prenatal phthalate metabolite concentrations and serum hormone concentrations (testosterone, 17-OH-progesterone, and IGF-1) as well as number of ovarian follicles in puberty. Positive significant correlations were found between prenatal phthalate exposure and FSH and sex hormone-binding globulin concentrations. Combined analyses of phthalate exposure (weighted quantile sums) showed significant negative associations with IGF-1 concentration and uterine volume as well as a significant positive association with LH concentration. LIMITATIONS, REASONS FOR CAUTION Phthalate metabolites were measured in serum from single prenatal maternal blood samples and cord blood samples. Potential concomitant exposure to other endocrine-disrupting environmental chemicals before or after birth was not controlled for. The study population size was limited. WIDER IMPLICATIONS OF THE FINDINGS Our results support the need for further research into possible adverse effects of environmental chemicals during foetal development of the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S) The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065). No conflicts of interest are declared. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The structural complexity of high-tech industries is often compromised by a combination of thermal, mechanical, and geometric weaknesses. New generation materials and engineering the structure of materials are among the techniques that engineers employ to eliminate these effects. In this study, a comprehensive analysis solution is derived using Lekhnitskii's complex variable approach with the use of general mapping functions, the concept of functionally graded materials (FGMs), and holomorphic functions in the form of Laurent series. This general solution is used for the thermoelastic analysis of perforated functionally graded carbon nanotube-reinforced composite (FG-CNTRC) plates with polygonal hole. A refined-calibrated rule of mixtures is used to approximate the material property of FG-CNTRC plates according to gradational changes in direction of thickness and available molecular dynamics simulations results. After validation of present analytical solution results with finite element analysis results and available mechanical analysis of composite plates results, stress and moment resultants due to remoting heat flux-mechanical loading is studied. The effect of FG-CNTRC material properties, heat flux condition, and four parameters affecting the shape of the polygonal holes has been investigated. During the present parametric analysis, the results clearly show that the parameters related to the FG-CNTRC material properties, flux conditions, and hole geometry each provide a reliable tool for designers to influence the stress and moment resultants to minimize undesirable stresses. This general formulation is able to calculate thermoelastic parameters (thermal and mechanical parameters, separately) for the generalized problems of the FGM plate or composite laminates with a polygonal hole. [ABSTRACT FROM AUTHOR]

Purpose: To determine vision‐related quality of life (VR‐QoL) and functional and structural parameters associated with VR‐QoL in patients with glaucoma before and 12 months after trabeculectomy. Methods: Fifty‐eight patients undergoing trabeculectomy were included. Participants completed the 25‐item National Eye Institute Visual Function Questionnaire (VFQ‐25) prior to and 12 months after trabeculectomy. Functional (visual acuity and visual fields) and structural (ganglion cell layer volume) parameters were evaluated for their association with VR‐QoL using multiple linear regression of VFQ‐25 subscale scores. Intraocular pressure and the number of glaucoma medications were also included in the analyses. Results: The VFQ‐25 composite score did not change after trabeculectomy (before: 74.9; 12 months: 74.0; p = 0.512). The subscale mental health had a significantly higher score 12 months after trabeculectomy (before: 65.6; 12 months: 71.4; p = 0.017). The VFQ‐25 scores for general health (before: 68.5; 12 months: 62.5; p = 0.009) and role difficulties (before: 78.9; 12 months: 53.7; p < 0.001) were significantly lower 12 months after trabeculectomy. No functional or structural parameters were associated with VFQ‐25 composite score. Conclusion: Overall, VR‐QoL in glaucoma patients was similar before and after trabeculectomy, reflecting the procedure's stabilizing effect on both objective and subjective visual function. The absence of correlations between VR‐QoL and clinical parameters emphasizes the multifaceted nature of VR‐QoL and highlights the limitations of depending solely on objective clinical metrics to evaluate patients' subjective experiences. Using both objective measures and VR‐QoL, clinicians can better understand the challenges patients face due to glaucoma and trabeculectomy, potentially leading to better solutions. [ABSTRACT FROM AUTHOR]

Background: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT. Study Design and Methods: We created a database of all FMT treatments (n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT. Results: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58–72%) and 72% (CI 95% 66–79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73–85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure. Discussion: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable. [ABSTRACT FROM AUTHOR]

Background Endogenous sex steroids influence the pubertal growth spurt and adult height. However, the impact of puberty suppression and sex steroids on growth in transgender adolescents is sparsely studied. Aim We investigated pubertal growth, serum IGF-I and IGF binding protein-3 (IGFBP-3), and adult height of transgender adolescents receiving hormone therapy. Methods Observational study of a national cohort (2016-2023) comprising 219 transgender adolescents <18 years of age. Treatment consisted of gonadotropin-releasing hormone agonist combined with estradiol or testosterone (adjusted to serum concentrations between 0 and +2 SDs corresponding to the gender identity). Results Adult height was within ±2 SD for sex assigned at birth. Most trans girls reached adult height within references of girls. For trans girls (bone age ≤15 years before treatment), a growth spurt was observed during estradiol therapy. IGF-I and height SD score (SDS) declined during oral estradiol administration (−0.13 SDS per month, P =.059, and −0.02 SDS, P =.001, respectively). We observed significantly lower adult height compared to target height for trans girls (−2.7 cm, P =.01) and significant differences between height SDS before treatment and at adult height (−0.35 SDS, P <.001). Half of the trans boys remained short (<−2 SD) compared to references for boys, and most completed growth spurt before initiation of treatment. IGFBP-3 declined following testosterone treatment. There was a significant difference between height SDS before treatment and at adult height (−0.17 SDS, P <.001). Discussion and Conclusion The minor reduction in adult height of trans girls after hormone treatment may be beneficial to some, whereas trans boys did not experience height gain. [ABSTRACT FROM AUTHOR]

Neuromuscular blocking agents are used commonly to induce skeletal muscle relaxation during surgery. While muscle relaxation facilitates surgical procedures and tracheal intubation, adequate recovery of muscle function after surgery is required to support pulmonary function, and even mild residual neuromuscular block increases the risk of severe postoperative pulmonary complications. While recovery of muscle function after surgery involving neuromuscular blocking agents can be monitored and, in addition, be accelerated by use of current antagonists (reversal agents), there is a clear clinical need for a safe drug to antagonize all types of neuromuscular blocking agents. Here, we show that inhibition of the skeletal muscle-specific chloride ion (Cl-) channel, the ClC-1 channel, markedly accelerates recovery of both single contraction (twitch) and, important physiologically, sustained (tetanic) contractions in a rat model mimicking neuromuscular blocking agent-induced muscle block used during surgery. This suggests ClC-1 inhibition as a mechanism for fast and efficacious recovery of neuromuscular function induced by any neuromuscular blocking agents. Reversal agents are intravenous drugs used to accelerate recovery from neuromuscular block post-surgery. We report that inhibition of ClC-1, a skeletal muscle chloride channel, reverses any nondepolarizing blocking agent, providing a novel reversal (antagonism) mechanism. [ABSTRACT FROM AUTHOR]

Purpose: We present a probabilistic approach to medical image analysis that requires, and makes use of, explicit prior information provided by a medical expert. Depending on the choice of prior model the method can be used for image enhancement, analysis, and segmentation. Methods: The methodology is based on a probabilistic approach to medical image analysis, that allows integration of 1) arbitrarily complex prior information (for which realizations can be generated), 2) information about a convolution operator of the imaging system, and 3) information about the noise in the reconstructed image into a posterior probability density. The method was demonstrated on positron emission tomography (PET) images obtained from a phantom and a patient with lung cancer. The likelihood model (multivariate log-normal) and the convolution operator were derived from phantom data. Two examples of prior information were used to show the potential of the method. The extended Metropolis-Hastings algorithm, a Markov chain Monte Carlo method, was used to generate realizations of the posterior distribution of the tracer activity concentration. Results: A set of realizations from the posterior was used as the base of a quantitative PET image analysis. The mean and variance of activity concentrations were computed, as well as the probability of high tracer uptake and statistics on the size and activity concentration of high uptake regions. For both phantom and in vivo images, the estimated images of mean activity concentrations appeared to have reduced noise levels, and a sharper outline of high activity regions, as compared to the original PET. The estimated variance of activity concentrations was high at the edges of high activity regions. Conclusions: The methodology provides a probabilistic approach for medical image analysis that explicitly takes into account medical expert knowledge as prior information. The presented first results indicate the potential of the method to improve the detection of small lesions. The methodology allows for a probabilistic measure of the size and activity level of high uptake regions, with possible long-term perspectives for early detection of cancer, aswell as treatment, planning, and follow-up. [ABSTRACT FROM AUTHOR]

Bracken ferns (genus Pteridium) are among the most prevalent plants worldwide, with their distribution expanding due to their invasive nature. The environmental implications of their proliferation in areas affected by human activity, natural disasters, or land-use changes are concerning, primarily because of the carcinogenic illudane glycosides they produce. These compounds cause domestic and wildlife animal poisoning, as well as contamination of dairy products and drinking water. Several illudane glycosides are known, but usually only ptaquiloside (PTA) is monitored. This study investigates the spatial and temporal variations in illudane glycosides PTA, caudatoside (CAU) and ptesculentoside (PTE) across two phenotypes of Pteridium aquilinum (vars. aquilinum and latiusculum) over a broad geographic range spanning Denmark, Sweden, and Finland, encompassing 66 locations. We analysed different parts of the fern fronds (the tips and the lowest pinnae) using LC–MS and statistically explored the influence of phenotype, frond part, geographic location, sunlight exposure, and the surrounding ecosystem on glycoside content. Our findings reveal that PTA accounts for approximately two-thirds of the total illudane glycoside content, followed by CAU at nearly one-third, and a minor contribution from PTE. Glycoside levels were not influenced by phenotypic varieties or the studied environmental factors, but were significantly affected by geographic location. Specifically, CAU levels increased progressively towards the northeast, while PTA concentrations were highest in Denmark and markedly decreased in northeastern countries by over threefold, presumably due to climatic gradient. It has been further supported by temporal analysis in selected PTA-dominant regions indicating a reduction in PTA towards the end of the growing season, aligning its levels with those of CAU. Our study highlights that CAU concentrations in bracken ferns may equal or surpass PTA, contesting the prevailing view that PTA is the only notable illudane glycoside in Bracken. To provide unbiased assessment of the potential risks posed by P. aquilinum in the region, environmental and toxicological research should include measurements of not only PTA, but also CAU and, if possible, PTE. [ABSTRACT FROM AUTHOR]

This work aims to develop and apply an algorithm for solving space‐time fractional reaction‐advection diffusion (STFRAD) nonlinear coupled equations with specified initial and boundary conditions by employing a Shifted Legendre Gauss‐Lobatto collocation (SLGLC) scheme. The fractional derivatives of time and space are defined in Caputo sense. The approximate solutions have been constructed with the help of shifted Legendre polynomials. The proposed numerical scheme reduces the coupled fractional order differential equations into a system of algebraic equations which can then be easily solved. The error analysis through the two test problems is carried out to validate the efficiency and efficacy of the method. The effect of advection and reaction terms, and various space‐time fractional order derivatives on the solution profiles have been studied and are shown graphically for different particular cases. It has been observed that the species whose transport is simulated using STFRADE shows higher concentration at a specific distance in porous media in case of integer order differential equations as compared to fractional order equations demonstrating overestimation of its impact in case of integer order differential equation. This is extremely important observation with respect to applications in the field of groundwater pollution management. The salient feature of the article is the stability and convergence analyses of the proposed scheme on the concerned model, which demonstrates the effectiveness and capabilities of the developed method. [ABSTRACT FROM AUTHOR]

Knowledge of how to treat chronic tendinopathy has advanced in recent years, but the treatment of early tendinopathy is not well understood. The main purpose of this prospective observational study was to investigate if changes occur in clinical and imaging outcomes over 12 weeks in elite athletes with recent debut of tendinopathy. Sixty‐five elite adult athletes (24 ± 5 years) with early Achilles or patellar tendinopathy (symptoms < 3 months) were examined at baseline and after 12 weeks. Patients were divided into groups based on the duration of symptoms at the time of inclusion: (T1): 0–1 month, (T2): 1–2 months, or (T3): 2–3 months. Pain‐guided activity modification was the only intervention. We assessed the following clinical outcomes: Questionnaires (Victorian Institute of Sports Assessment (VISA)) and pain scores (0–10 numeric rating scale, NRS), structural outcomes from ultrasonography: Thickness, echogenicity, and Doppler flow, and from magnetic resonance imaging: Cross‐sectional area (CSA), thickness and length. Tendinopathic Achilles and patellar tendons displayed no significant differences on imaging tendon structural outcomes between T1 (n = 19), T2 (n = 23), and T3 (n = 20) at baseline or after 12 weeks, with one exception: Patellar tendons in T1 were thicker than T2 and T3 at baseline. Although athletes improved clinically on VISA and most NRS scores after 12 weeks, affected tendons with greater thickness, CSA and Doppler flow than contralateral tendons at baseline remained unchanged after 12 weeks. In conclusion, these data suggest that early tendinopathy in elite athletes can improve clinically after 12 weeks while morphology remains unchanged. [ABSTRACT FROM AUTHOR]

The genome editing technology CRISPR is described as a technological game-changer because of its flexibility and precision, and as an ethical game-changer due to its ability to engineer traits in living organisms without crossing species, avoiding a significant objection to genetically modified organisms (GMOs). In salmon farming, applications of CRISPR in breeding hold the promise of handling environmental and fish welfare challenges yet require social acceptance. Adopting an empirical bioethics framework, this stakeholder interview study shows that respecting species borders is important, but not decisive, for acceptance among Norwegian stakeholders. The main objections are based on moral reflections about technology use and outcomes. These reflections combine principles and pragmatic deliberations of moral costs and benefits, suggesting that CRISPR applications with environmentally and ethically significant benefits can be socially acceptable. This indicates that the game-changing potential of CRISPR relies on the characteristics of the editing and the context in which the application takes place. [ABSTRACT FROM AUTHOR]

How do capacity constraints affect the slope of the Phillips curve? In particular, do changes in output affect prices by more when firms face more strongly diminishing returns? Intuitively, one may conjecture that the answer is yes. With more strongly diminishing returns, marginal costs increase more when production increases, also raising prices by more. But this intuition is incomplete in models with sticky prices à la Calvo. In the standard New Keynesian model with Calvo pricing frictions, more strongly diminishing returns actually flatten the Phillips curve. The reason is the reluctance of firms who alter their prices to let their prices get too far out of line with the prices set by firms that do not adjust. We explain how the Phillips curve might be amended to avoid this implausible feature, for example, by using Rotemberg pricing or introducing wage stickiness. [ABSTRACT FROM AUTHOR]

This field study set out to test whether consumers' history of making decisions in a particular choice context moderated the effectiveness of a nudge intervention to reduce meat consumption. In a Danish hospital canteen that served both staff members and visitors, a combination of nudges (Chef's recommendation sticker + prominent positioning) was implemented to promote vegetarian sandwiches. The sales of these sandwiches increased from 16.45% during the baseline period to 25.16% during the nudge intervention period. Most notably, this increase was caused by the visitors, who had weak location-bound preferences. Hospital staff members (who had strong location-bound preferences) were unaffected by the nudge in their choice. This is an important finding because the two consumer groups did not differ on their person-bound preferences for meat. It seems that behaviour change is best predicted by location-bound preferences, whereas the behaviour itself is best predicted by person-bound preferences. These findings can help organizations in estimating whether a nudge intervention has enough potential for behaviour change, or whether more directive policies are required. [ABSTRACT FROM AUTHOR]

More than half of water supply in the western United States is sourced from forested lands that are increasingly under wildfire risk. Studies have begun to isolate the effects of wildfire on streamflow, but they have typically used coarse temporal resolutions that cannot account for the numerous, interconnected watershed processes that control the responses to rainfall events. In this study, we employed a method to isolate fine‐scale (daily) effects of fire. Wildfire effects were estimated as the difference between measured post‐fire streamflow and unburned scenarios of post‐fire streamflow simulated by a hydrologic model calibrated to pre‐fire conditions. The method was applied to track hydrologic recovery after wildfires in six burned watersheds across the western United States: North Eagle Creek, NM (2012 Little Bear Fire), Lopez Creek, CA (1985 Las Pilitas Fire), City Creek, Devil Canyon Creek, East Twin Creek, and Plunge Creek, CA (2003 Old Fire). All six watersheds experienced prolonged increases of post‐fire streamflow, with the most consistent changes occurring during periods of low streamflow. Following 6 years of increased streamflow, Lopez Creek experienced 6 years of reduced streamflow before returning to the pre‐fire hydrologic regime. North Eagle Creek and the four watersheds affected by the Old Fire continued to have elevated streamflow 9 and 18 years post‐fire, respectively, without returning to the pre‐fire hydrologic regime. [ABSTRACT FROM AUTHOR]

Since the fundamental works of Kachanov and Rabotnov, creep damage mechanics is an established field of research in solid mechanics. The starting point is the creep behavior of materials under moderate loads but elevated temperatures. The final stage of creep behavior is accompanied by damage and other microstructural changes such as embrittlement. In the present paper a detailed analysis of literature is given. A special focus is made on the different types of representation of damage by scalar, vectorial and tensorial variables. In addition, some Russian sources are presented which are not widely known yet. The survey is representative, but not complete - due to the large number of sources, it is not possible to provide a complete overview. Considering the huge number of parameters of tensorial damage variables which should be established experimentally in the second part of the paper a simple model for the high temperature creep and embrittlement in metals and alloys under conditions of the long-term usage is introduced. The model is an extension of R. Arutunyan's model developed in the 90th of the last century. The extension includes the consideration of a compressible medium, the introduction of the mass conservation law and true stress, and definition of the damage parameter as a relative change in the density of the material. The parameters are experimentally estimated and the comparison of simulations and experiments is given. [ABSTRACT FROM AUTHOR]

Objectives: The World Health Organization's definition of oral epithelial dysplasia includes differentiated dysplasia, which is defined by purely architectural abnormalities of oral mucosa without cytological changes. We analysed differentiated dysplasia's frequency, progression risk and correlation with oral brush cytology. Materials and Methods: Cytoarchitectural criteria and expression patterns of keratin 13/17 and ki67 were studied in oral biopsies clinically diagnosed with leukoplakia. Biopsies were assessed for dysplasia and its grade. Available brush cytology findings were obtained from clinical records. Results: We included 159 biopsies from 112 patients (33% differentiated dysplasia; 27% keratosis without dysplasia; oral epithelial dysplasia with atypia of mild, moderate and severe degree including invasive cancers in 9%, 8% and 7%, respectively). Keratin 13 loss and keratin 17 gain were higher in differentiated‐dysplasia cases (p < 0.0001), which had the highest hypergranulosis frequency. Keratin 17 expression was associated with higher malignant‐transformation rates (p = 0.0028). The transformation rate and time were comparable between dysplasia with atypia and differentiated‐dysplasia cases, which had higher progression rates and shorter time periods than keratosis cases without dysplasia (p = 0.08). Cytology prior to differentiated dysplasia all indicated normal oral mucosa. Conclusions: Keratin 17 but not oral brush cytology can help identify patients with differentiated dysplasia with higher risk for malignant transformation. [ABSTRACT FROM AUTHOR]

Most of the evidence regarding the success of ACOs is from the Medicare program. This review evaluates the impacts of ACOs within the Medicaid population. We identified 32 relevant studies published between 2012 and 2023 which analyzed the association of Medicaid ACOs and health care utilization (n = 21), quality measures (n = 18), health outcomes (n = 10), and cost reduction (n = 3). The results of our review regarding the effectiveness of Medicaid ACOs are mixed. Significant improvements included increased primary care visits, reduced admissions, and reduced inpatient stays. Cost reductions were reported in a few studies, and savings were largely dependent on length of attribution and years elapsed after ACO implementation. Adopting the ACO model for the Medicaid population brings some different challenges from those with the Medicare population, which may limit its success, particularly given differences in state Medicaid programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Bilateral ovariectomy in mares with behavioral problems is a common long-term solution with high owner satisfaction. However, a pathohistological explanation for behavioral improvement after surgery is lacking. Therefore, bilaterally removed, clinically unremarkable ovaries from mares with behavioral problems were immunohistologically evaluated and compared with pathohistologically confirmed granulosa cell tumors. A complete data set including clinical history, clinical examination, serum anti-Müllerian hormone (AMH), and testosterone concentrations was analyzed as the basis for the pathohistological study. Immunohistochemical evaluation of Ki-67, AMH, aromatase, epidermal growth factor receptor, calretinin, and epithelial cadherin revealed no clear differentiation between large follicular structures of clinically unremarkable ovaries and cyst-like structures of neoplastic ovaries. Clinical data and success rate after bilateral ovariectomy of 85% were comparable with previous studies. Preoperatively measured serum AMH and testosterone concentrations were indicative of advanced granulosa cell tumors but were variable in mares with clinically unremarkable ovaries. Ultrasonographically nondetectable early neoplastic changes could be determined in 15% of mares and anovulatory-like follicles in 30% of mares with bilaterally removed ovaries. These changes might be a pathohistological explanation for behavioral problems of ovarian origin and a reason for the high success rate of bilateral ovariectomy. Behavioral problems in reproductively healthy mares are a challenging issue that is successfully treated with bilateral ovariectomy (BO). This laparoscopic procedure represents an alternative to conservative treatment for mares not intended for breeding and results in high owner satisfaction regarding behavioral improvement. However, a pathohistological explanation to justify surgical ovarian removal regarding animal welfare is lacking. Therefore, the objective of this study was to pathohistologically evaluate bilaterally removed, clinically unremarkable ovaries of mares with behavioral problems (bOE, n = 20) and to compare them with pathohistologically confirmed granulosa cell tumors of mares with neoplastic ovaries (GCT-uOE, n = 10). A complete data set including preliminary presentation, clinical examination, and serum anti-Müllerian hormone (AMH) and testosterone was further analyzed in both groups. Both hormones were significantly higher in GCT-uOE compared with bOE. Immunohistochemical expression of Ki-67, AMH, aromatase, epidermal growth factor receptor, calretinin, and epithelial cadherin in granulosa cells of large follicular structures in bOE did not differ from neoplastic granulosa cells in GCT-uOE. Ultrasonographically nondetectable early neoplastic changes were pathohistologically evaluated in 15% of mares and anovulatory-like follicles in 30% of mares in bOE and might be one explanation for the high success rate of BO in 85% of bOE in this study. [ABSTRACT FROM AUTHOR]

Simple Summary: Male breast cancer (MBC) is a rare condition, and the role of low HER2 expression (HER2 low) is not well understood. In this prospective study, 870 MBC patients treated between May 2009 and June 2023 were evaluated to investigate the prognostic significance of HER2 low status. After a median follow-up of 43 months, 659 patients were classified into three groups: 76% were HER2 low, 12.3% were HER2 zero, and 11.7% were HER2 positive. HER2 positivity was linked to younger age, higher tumor proliferation, and more aggressive cancer characteristics, but no differences were found between HER2 zero and HER2 low groups. Furthermore, HER2 low status did not influence disease-free or overall survival. However, HER2 low has a potential clinical impact on MBC as a treatment target. Background: Male breast cancer (MBC) is a rare disease, and the potential influence of low expression of human epidermal growth factor receptor 2 (HER2 low) remains unexplored. Methods: In this prospective cohort study, we evaluated 870 patients treated for MBC between May 2009 and June 2023 to assess HER2 low status and its prognostic implications. Results: With a median follow-up of 43 months (range 1–175 months), 659 eligible patients were categorized into three groups based on HER2 status: 501 (76%) HER2 low, 81 (12.3%) HER2 zero, and 77 (11.7%) HER2 positive. HER2 positivity correlated with younger age, higher proliferation index, non-specific type histology, lymphovascular invasion (LVSI), and low differentiation grade. Notably, all these parameters were equally distributed between the HER2 zero and HER2 low groups. Additionally, HER2 positivity was significantly associated with increased occurrences of regional and distant lymph nodes and pulmonary metastases. However, no statistically significant difference was observed between HER2 zero and HER2 low. Disease-free and overall survival showed no significant disparities between the groups. Conclusions: Our findings suggest that HER2 low status is frequently detected in MBC. Despite this, HER2 low did not correlate with clinical and pathological parameters, nor did it impact patients' survival. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between the use of drugs for hypertension or heart failure, particularly diuretics, and risk of death in COVID-19. Methods: We conducted a cohort study, based on record linked individual-based data from national registers, of all Swedish inhabitants 50 years and older (n = 3,909,321) at the start of the first SARS-CoV-2 wave in Sweden. The association between use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), thiazides, loop diuretics, aldosterone antagonists, beta blocking agents and calcium channel blockers at the index date 6 March 2020, and death in COVID-19 during 7 March to 31 July 2020, was analysed using Cox-proportional hazards regression, adjusted for a wide range of possible confounders. Results: Use of loop diuretics was associated with higher risk [adjusted hazard ratio (HR) 1.26; 95% confidence interval (95% CI) 1.17–1.35] and thiazides with reduced risk (0.78; 0.69–0.88) of death in COVID-19. In addition, lower risk was observed for ACEI and higher risk for beta-blocking agents, although both associations were weak. For ARB, aldosterone antagonists and calcium channel blockers no significant associations were found. Conclusion: In this nationwide cohort of nearly 4 million persons 50 years and older, the use of loop diuretics was associated with increased risk of death in COVID-19 during the first SARS-CoV-2 wave in Sweden. This contrasted to the decreased risk observed for thiazides. As treatment with loop diuretics is common, particularly in the elderly, the group most affected by severe COVID-19, this finding merit further investigation. [ABSTRACT FROM AUTHOR]

Child abuse is a severe global problem associated with various negative consequences. It is therefore important that the services received at Child Advocacy Centers (CACs) are perceived as positive as possible by children affected by abuse. Preliminary research indicates that CACs are successful in terms of providing coordinated, professional services. However, existing research has primarily focused on service and criminal justice system outputs, rather than documenting the experiences of the target group: i.e., children undergoing the CAC proceedings. The present study seeks to investigate the children's experiences of the forensic procedures in a CAC. Qualitative interviews were conducted with 15 children undergoing case proceedings at a Danish CAC. The overall experiences of the children of the forensic interview and forensic medical examination were documented. Additionally, five overall themes were constructed using Thematic Analysis: Localities and surroundings, Relational and communicative work, Ambivalent experiences, Need of information and overview, and Missing out on everyday life. The findings of the current study underline the importance of the physical environment of the CAC, the need of information and overview as well as strong relational and communicative skills among professional as core elements in establishing positive encounters with the CAC. Furthermore, the results indicate how negative experiences of visiting a CAC are not necessarily directly linked to the CAC but may be a result of the children experiencing missing out on well-liked everyday activities. Altogether these results are important to consider when planning future CAC visits to support the well-being of the child. [ABSTRACT FROM AUTHOR]

Mesoscale eddies cause deviations from the background physical and biogeochemical states of the oligotrophic oceans, but how these perturbations manifest in microbial ecosystemfunctioning, such as communitymacromolecular composition or carbon export, remains poorly characterized. We present comparative lipidomes from communities entrained in two eddies of opposite polarities (cyclone-anticyclone) in the North Pacific Subtropical Gyre (NPSG). A previous work on this two-eddy system has shown differences in particulate inorganic carbon (PIC) and biogenic silica sinking fluxes between the two eddies despite comparable total organic carbon fluxes. We measured the striking differences between the lipidomes of suspended and sinking particles that indicate taxon-specific responses to mesoscale perturbations. Specifically, cyanobacteria did not appear to respond to increased concentrations of phosphorus in the subsurface of the cyclonic eddy, while eukaryotic microbes exhibit P-stress relief as reflected in their lipid signatures. Furthermore, we found that two classes of lipids drive differences between suspended and sinking material: sinking particles are comparatively enriched in phosphatidylcholine (PC, amembrane-associated lipid) and triacylglycerol (TAG, an energy storage lipid). We observed significantly greater export of TAGs from the cyclonic eddy as compared to the anticyclone and found that this flux is strongly correlated with the concentration of ballast minerals (PIC and biogenic silica). This increased export of TAGs from the cyclone, but not the anticyclone, suggests that cyclonic eddy perturbationsmay be amechanism for the delivery of energy-rich organic material below the euphotic zone. [ABSTRACT FROM AUTHOR]

Background: Clustering of sequences into operational taxonomic units (OTUs) and denoising methods are a mainstream stopgap to taxonomically classifying large numbers of 16S rRNA gene sequences. Environment-specific reference databases generally yield optimal taxonomic assignment. Results: We developed SpeciateIT, a novel taxonomic classification tool which rapidly and accurately classifies individual amplicon sequences (https://github.com/Ravel-Laboratory/speciateIT). We also present vSpeciateDB, a custom reference database for the taxonomic classification of 16S rRNA gene amplicon sequences from vaginal microbiota. We show that SpeciateIT requires minimal computational resources relative to other algorithms and, when combined with vSpeciateDB, affords accurate species level classification in an environment-specific manner. Conclusions: Herein, two resources with new and practical importance are described. The novel classification algorithm, SpeciateIT, is based on 7th order Markov chain models and allows for fast and accurate per-sequence taxonomic assignments (as little as 10 min for 107 sequences). vSpeciateDB, a meticulously tailored reference database, stands as a vital and pragmatic contribution. Its significance lies in the superiority of this environment-specific database to provide more species-resolution over its universal counterparts. [ABSTRACT FROM AUTHOR]

Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection. Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ Tcells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests. Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response. Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections. [ABSTRACT FROM AUTHOR]

Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling. Microbial carbon use efficiency (CUE) is crucial for carbon storage, but its variability is difficult to capture due to inconsistent measurements and complex interactions. This perspective proposes integrating diverse data and models to improve CUE in carbon cycle models [ABSTRACT FROM AUTHOR]

It is expected that machine learning algorithms will enable better diagnosis, prognosis, and treatment in psychiatry. A central argument for deploying algorithmic methods in clinical decision-making in psychiatry is that they may enable not only faster and more accurate clinical judgments but also that they may provide a more objective foundation for clinical decisions. This article argues that the outputs of algorithms are never objective in the sense of being unaffected by human values and possibly biased choices. And it suggests that the best way to approach this is to ensure awareness of and transparency about the ethical trade-offs that must be made when developing an algorithm for mental health. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori colonizes the human stomach and may affect the inflammatory response, hormone production related to energy regulation, and gastrointestinal microbiota composition. Previous studies have explored a potential association between H. pylori infection and pediatric obesity with varying results. Considering the immunomodulatory effects of early-life infection with H. pylori that can confer beneficial effects, we hypothesized that we would find an inverse relationship between H. pylori seropositivity and obesity among Danish children and adolescents. Methods: We assessed H. pylori seroprevalence in 713 subjects from an obesity clinic cohort and 990 subjects from a population-based cohort, aged 6 to 19 years, and examined its association with obesity and other cardiometabolic risk factors. Results: No association was found between H. pylori and body mass index standard deviation score (BMI SDS). H. pylori seropositivity was, however, significantly associated with higher fasting plasma glucose levels and the prevalence of hyperglycemia. Conclusion: While we did not find an association between H. pylori seropositivity and BMI SDS, we observed a significant association with higher fasting plasma glucose levels and increased prevalence of hyperglycemia, suggesting that H. pylori infection may contribute to impaired glucose regulation in Danish children and adolescents. [ABSTRACT FROM AUTHOR]

Harvesting waste heat efficiently with thermoelectric energy conversion requires materials with low thermal conductivity. Recently, it was demonstrated how dynamic lone pair expression in thermoelectric InTe is responsible for giant anharmonicity leading to a very low lattice thermal conductivity. InTe also contains correlated disorder of intrinsic defects due to vacancies, and this contributes to additional lowering of the thermal conductivity. Here we use the three‐dimensional difference pair distribution function (3D‐ΔPDF) to analyze 25 K single crystal diffuse X‐ray scattering from InTe to unravel the local defect structure, and propose a microscopic structural model. Extended off‐centering of In+ ions induced by vacancies allows for the local expression of stereochemically active lone pairs. The associated electronic stabilization is proposed to be a driving force for the formation of In+ vacancy defects in InTe. [ABSTRACT FROM AUTHOR]

Background: Food and beverage companies play a central role in shaping the healthfulness of food environments. Methods: The BIA-Obesity tool was used to evaluate and benchmark the specificity, comprehensiveness and transparency of the food environment-related policies and commitments of leading food and beverage manufacturing and retailing companies in Canada. Policies and commitments related to the healthfulness of food environments within 6 action areas were assessed: 1) corporate nutrition strategy; 2) product (re)formulation; 3) nutrition information and labelling; 4) product and brand promotion; 5) product accessibility; and 6) disclosure of relationships with external organizations. Data were collected from publicly available sources, and companies were invited to supplement and validate information collected by the research team. Each company was then assigned a score out of 100 for each action area, and an overall BIA-Obesity score out of 100. Results: Overall BIA-Obesity scores for manufacturers ranged from 18 to 75 out of 100 (median = 49), while scores for retailers ranged from 21 to 25 (median = 22). Scores were highest within the product (re)formulation (median = 60) followed by the corporate nutrition strategy (median = 59) domain for manufacturers, while retailers performed best within the corporate nutrition strategy (median = 53), followed by the disclosure of relationships with external organizations (median = 47) domain. Companies within both sectors performed worst within the product accessibility domain (medians = 8 and 0 for manufacturers and retailers, respectively). Conclusions: This study highlights important limitations to self-regulatory approaches of the food and beverage industry to improve the healthfulness of food environments. Although some companies had specific, comprehensive, and transparent policies and commitments to address the healthfulness of food environments in Canada, most fell short of recommended best-practice. Additional mandatory government policies and regulations may be warranted to effectively transform Canadian food environments to promote healthier diets and prevent related non-communicable diseases. [ABSTRACT FROM AUTHOR]