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Abstract To enable detailed study of a wide variety of future health challenges, we have created future land use maps for the Netherlands for 2050, based on the Dutch One Health Shared Socio-economic Pathways (SSPs). This was done using the DynaCLUE modelling framework. Future land use is based on altitude, soil properties, groundwater, salinity, flood risk, agricultural land price, distance to transport hubs and climate. We also account for anticipated demand for different land use types, historic land use changes and potential spatial restrictions. These land use maps can be used to model many different health risks to people, animals and the environment, such as disease, water quality and pollution. In addition, the Netherlands can serve as an example for other rapidly urbanising deltas where many of the health risks will be similar.

Abstract Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in

Abstract Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

Abstract Introduction Growth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated in OCOG-ALMERA (NCT02115464), a phase II randomized clinical trial, that investigated metformin in combination with standard of care concurrent chemoradiotherapy (cCRT). OCOG-ALMERA was not able to demonstrate benefit in the metformin arm. Therefore, biomarker studies are needed to better define stratification parameters for future trials. Methods Patients were randomized to treatment with platinum-based chemotherapy and concurrent chest radiotherapy (60–66 Gy), with or without metformin (2000 mg/d). The trial collected tumor volume parameters, survival outcomes, and patient blood plasma at baseline, during (weeks 1 and 6) and 6 months after cCRT. Plasma GDF15 levels were assayed with the ELISA method. Statistical analyses explored associations between GDF15, survival outcomes, and radiotherapy tumor volumes. Results Baseline plasma levels of GDF15 were elevated in study patients, they increased during cCRT (p

Abstract Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP is characterized by increased bacterial RNA mass and dominance of culture-confirmed pathogens, detectable days prior to 2°BP clinical diagnosis, and frequently also present in nasal swabs. Assessment of the pulmonary transcriptome reveals suppressed TNFα signaling in patients with 2°BP, and sensitivity analyses suggest this finding is mediated by corticosteroid treatment. Further, we find that increased bacterial RNA mass correlates with reduced expression of innate and adaptive immunity genes in both 2°BP patients and controls. Taken together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP, and suggest that suppressed immune signaling, potentially mediated by corticosteroid treatment, permits expansion of opportunistic bacterial pathogens.

Abstract Background Hospitalization indicates the presence of severe disease and constitutes a leading cost in health care. We aimed to prospectively assess if prevalent diabetes mellitus contributes to excess all-cause and cause-specific hospital admissions and mortality at the population level. Methods We used a Swedish prospective population-based cohort, including 25,642 individuals of whom 4.2% had prevalent diabetes at baseline (mean age 61.2 ± 6.8 years, age range 44.8–73.4 years). We compared the number of hospitalizations and mortality classified according to the main chapters of the 10th revision of the International Classification of Diseases (ICD-10) during follow-up using nationwide inpatient registries, comparing individuals with and without prevalent diabetes, using multivariate adjusted negative binomial regression (incidence rate ratio, IRR) and Cox regression, respectively. Results During a median follow-up of 19 years, 18,904 subjects were hospitalized at least once [median 3 (IQR 2–6)] and 6767 (26.4%) individuals died. Overall, subjects with diabetes were hospitalized (IRR 1.83, p

Lung cancer is the leading cause of cancer-related deaths in Canada, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Timely access to comprehensive molecular profiling is critical for selecting biomarker-matched targeted therapies, which lead to improved outcomes in advanced NSCLC. Tissue biopsy samples are the gold standard for molecular profiling; however, several challenges can prevent timely and complete molecular profiling from being performed, causing delays in treatment or suboptimal therapy selection. Liquid biopsy offers a minimally invasive method for molecular profiling by analyzing circulating tumour DNA (ctDNA) and RNA (cfRNA) in plasma, potentially overcoming these barriers. This paper discusses the outcomes of a multidisciplinary working group in Ontario, which proposed three eligibility criteria for liquid biopsy reimbursement: (1) insufficient tissue for complete testing or failed tissue biomarker testing; (2) suspected advanced NSCLC where tissue biopsy is not feasible; and (3) high-risk patients who may deteriorate before tissue results are available. The group also addressed considerations for assay selection, implementation, and economic impact. These discussions aim to inform reimbursement and implementation strategies for liquid biopsy in Ontario’s public healthcare system, recognizing the need for ongoing evaluation as technology and evidence evolve.

Abstract Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

Abstract We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 92.5 days (range: 22–210 days) after CAR-T therapy and a median of 85 days after cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis and villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR T-cell presence was confirmed within the lamina propria. Systemic corticosteroids were initiated in 10 patients (71%) a median of 25.5 days following symptom onset, with symptom improvement in 40%. Subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. Five patients (36%) have died from bowel perforation or treatment-emergent sepsis. In conclusion, IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1–3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.

Abstract The benefits of pulmonary rehabilitation (PR) and palliative care (PC) as non-pharmacological therapies for people with idiopathic pulmonary fibrosis (IPF) are increasingly being recognised but in the UK the proportion of people with this life-limiting condition who are referred to such services is thought to be low. This retrospective cohort study aimed to describe trends in referrals to PR and PC services among people with IPF over a 10-year period and to identify factors associated with non-referral. Our study cohort was drawn from the UK’s pseudonymised Clinical Practice Research Datalink (CPRD) Aurum primary care database and comprised 17,071 individuals diagnosed with IPF between 2010 and 2019. While 12.0% of IPF patients were offered a referral to PR, less than 2% completed a PR programme. Around a fifth (19.4%) received a referral to generic PC support services; however, this is well below reported PC referral rates for lung cancer patients. Moreover, the majority of PC referrals occurred late; among those who died, 31% were referred within a month and 70% within 6 months of death. Referrals to PR and PC had however increased (by around 2–fold and 4-fold, respectively) over the course of the study period. Factors associated with non-referral to PR included female sex, older age and co-diagnosis of dementia; barriers to PC referral included being female or of Asian or Black ethnicity. We also found evidence of regional differences in referrals. These findings confirm that PR and PC service provision for people with IPF across England is suboptimal.

Abstract Medication can affect the gut microbiota composition and function. The aim of this study was to investigate connections between use of common non-antibiotic medicines and the gut microbiota composition and function in a large Swedish cohort (N = 2223). Use of 67 medications and polypharmacy (≥ 5 medications), based on self-reported and prescription registry data, were associated with the relative abundance of 881 gut metagenomic species (> 5% prevalence) and 103 gut metabolic modules (GMMs). Altogether, 97 associations of 26 medications with 40 species and of four medications with five GMMs were observed (false discovery rate

Abstract Background Compassion is an essential and beneficial value in mental healthcare. However, how digital mental health interventions influence compassion in treatment has not been systematically investigated, due to the lack of appropriate measurement instruments. To address this gap, we developed the Compassionate Technology Scale for Professionals (CTS-P), aimed at mental health professionals. Methods We used Q-methodology, a method that combines quantitative and qualitative analysis to explore shared viewpoints on a particular topic, to select and refine items. Participants were 15 professionals from different areas of mental healthcare. In individual sessions, while thinking aloud, they sorted 35 statements on relevance for evaluating technology use on compassion. The statements were based on a scientific conceptualization of compassion with five elements. The sorting task was followed by a short interview to explore participants’ associations with compassion and technology. Results With by-person factor analysis, we found three different viewpoints among participants, all with eigenvalues > 1 and with a total explained variance of 63.02%. We selected prioritized items of each viewpoint and for each theoretical element of compassion, resulting in a full scale (15 items) and a short scale (3 items). Based on qualitative input from participants, the scale was adapted to clarify its focus and the wording of items. While thinking aloud, participants shared benefits and critical notes regarding technology and compassion. Discussion Together with key stakeholders, we developed the CTS-P. Most participants prioritized the potential of technology to obtain more information and be closer to their client in facilitating compassion. The main critical note participants had was that technology is not necessary to support compassion at the therapist’s experiential level. This emphasizes the need to further explore how mental health professionals and technology can complement each other in a system of compassionate care. Future research should explore the factor structure, validity, and reliability of the scale through psychometric validation. Conclusions The CTS-P can make the extent to which technology for mental healthcare influences elements of compassion measurable and comparable. The scale can prove useful for prioritizing the value of compassion in both the development and use of digital mental health interventions.

Abstract Grasspea (Lathyrus sativus L.) is an underutilised but promising legume crop with tolerance to a wide range of abiotic and biotic stress factors, and potential for climate-resilient agriculture. Despite a long history and wide geographical distribution of cultivation, only limited breeding resources are available. This paper reports a 5.96 Gbp genome assembly of grasspea genotype LS007, of which 5.03 Gbp is scaffolded into 7 pseudo-chromosomes. The assembly has a BUSCO completeness score of 99.1% and is annotated with 31719 gene models and repeat elements. This represents the most contiguous and accurate assembly of the grasspea genome to date.

Abstract The emission of high-order harmonics from solids under intense laser-pulse irradiation is revolutionizing our understanding of strong-field solid-light interactions, while simultaneously opening avenues towards novel, all-solid, coherent, short-wavelength table-top sources with tailored emission profiles and nanoscale light-field control. To date, broadband spectra in solids have been generated well into the extreme-ultraviolet (XUV), but the comparatively low conversion efficiency in the XUV range achieved under optimal conditions still lags behind gas-based high-harmonic generation (HHG) sources. Here, we demonstrate that two-color high-order harmonic wave mixing in a fused silica solid is more efficient than solid HHG driven by a single color. This finding has significant implications for compact XUV sources where gas-based HHG is not feasible, as solid XUV wave mixing surpasses solid-HHG in performance. Moreover, our results enable utilizing solid high-order harmonic wave mixing as a probe of structure or material dynamics of the generating solid, which will enable reducing measurement times compared to the less efficient regular solid HHG. The emission intensity scaling that follows perturbative optical wave mixing, combined with the angular separation of the emitted frequencies, makes our approach a decisive step for all-solid coherent XUV sources and for studying light-engineered materials.

Abstract Corrosion of critical metal components exacts a heavy toll in terms of maintenance and replacement costs and damage to ecosystems upon failure. Polymeric barrier coatings protect against corrosion; however, design principles for modulating polymer structure to improve corrosion inhibition remain contested and elusive. Here, we examine molecular-weight-dependent differences in the efficacy of corrosion inhibition on aluminum substrates afforded by polyetherimide (PEI) coatings. Analyses of coated substrates evidence a clear trend denoting improved corrosion inhibition for higher weighted-average molecular weight (M W) PEI. The more rigid and entangled macromolecular network of higher-M W variants exhibit stable impedance values, |Z|0.01 Hz ca. 1010 Ω/cm2, upon extended immersion in brine media, whereas lower-M W variants are readily hydrated and disentangled resulting in a significant reduction in impedance values. Results illuminate mechanistic understanding of molecular-weight-dependence in corrosion inhibition, advance a framework for considering the dynamical evolution of secondary structure, and exemplify generalizable design principles for corrosion inhibition.

Citizen science is a rapidly growing field, particularly among young scientists. In this case study, we review a year-long citizen science initiative hosted at Western University, Canada, which aimed to document and highlight biodiversity on campus while simultaneously seeking to improve community engagement with the environment. Using the popular citizen science platform iNaturalist, we facilitated data collection and community engagement through a combination of informal field surveys, undergraduate-level course assignments, social media, and passive data submission. Throughout the first year of the initiative, nearly 300 community members submitted 3716 observations of 1225 species, including observations of 103 species documented on iNaturalist for the first time in the region, and other species of ecological significance. This citizen science project underscores the strengths and utility of citizen science and provides a framework for other higher education institutions to develop similar initiatives.

Objective: Understanding both the positive and negative psychological outcomes among cancer patients during the pandemic is critical for planning post-pandemic cancer care. This study (1) examined levels of psychological distress and post-traumatic growth (PTG) among Canadian cancer patients during the COVID-19 pandemic and (2) explored variables that were associated with psychological distress and PTG during the pandemic using a biopsychosocial framework. Method: A cross-section survey was undertaken of patients receiving ongoing care at a regional cancer centre in Ontario, Canada, between February and December 2021. Self-reported questionnaires assessing sociodemographic information, social difficulties, psychological distress (depression, anxiety fear of recurrence, and emotional distress), PTG, illness perceptions, and behavioural responses to the pandemic were administered. Disease-related information was extracted from patient health records. Results: Prevalences of moderate to severe levels of depression, anxiety, fear of recurrence and emotional distress were reported by 26.0%, 21.2%, 44.2%, and 50.0% of the sample (N = 104), respectively. Approximately 43% of the sample reported experiencing high PTG, and these positive experiences were not associated with levels of distress. Social factors, including social difficulties, being female, lower education, and unemployment status were prominent associative factors of patient distress. Perceptions of the pandemic as threatening, adopting more health safety behaviours, and not being on active treatment also increased patient likelihood to experience severe psychological distress. Younger age and adopting more health safety behaviours increased the likelihood of experiencing high PTG. The discriminatory power of the predictive models was strong, with a C-statistic > 0.80. Conclusions: Examining both the positive and negative psychological patient outcomes during the pandemic has highlighted the complex range of coping responses. Interventions that adopt a multi-pronged approach to screen and address social distress, as well as to leverage health safety behaviours, may improve the adjustments in the pandemic aftermath.

Abstract Background The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. Methods Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES) and the 2013–2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. Results CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2–2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7–3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1–15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2–4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2–6.5) among patients aged 20–49 years and 2.2 (95%CI:2.1–2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5–12.1), Hispanic/Latino (10.9, 95%CI:10.5–11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20–49 had the highest CVE prevalence ratios. Conclusions These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.

Abstract Anxiety disorders is ranked as the most common class of mental illness disorders globally, affecting hundreds of millions of people and significantly impacting daily life. Developing reliable predictive models for anxiety treatment outcomes holds immense potential to help guide the development of personalised care, optimise resource allocation and improve patient outcomes. This research investigates whether community mental health treatment for anxiety disorder is associated with reliable changes in Kessler psychological distress scale (K10) scores and whether pre-treatment K10 scores and past health service interactions can accurately predict reliable change (improvement). The K10 assessment was administered to 46,938 public patients in a community setting within the Western Australia dataset in 2005–2022; of whom 3794 in 4067 episodes of care were reassessed at least twice for anxiety disorders, obsessive–compulsive disorder, or reaction to severe stress and adjustment disorders (ICD-10 codes F40–F43). Reliable change on the K10 was calculated and used with the post-treatment score as the outcome variables. Machine learning models were developed using features from a large health service administrative linked dataset that includes the pre-treatment K10 assessment as well as community mental health episodes of care, emergency department presentations, and inpatient admissions for prediction. The classification model achieved an area under the receiver operating characteristic curve of 0.76 as well as an F1 score, precision and recall of 0.69, and the regression model achieved an R2 of 0.37 with mean absolute error of 5.58 on the test dataset. While the prediction models achieved moderate performance, they also underscore the necessity for regular patient monitoring and the collection of more clinically relevant and contextual patient data to further improve prediction of treatment outcomes.

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management. Methods A three-year retrospective cohort study (2020–2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients. Results During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed. Conclusions CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures.

Intraoperative use of vasopressors in free flap surgeries is controversially debated. The predominant concern is that pedicle blood supply will decrease leading to post-operative complications. This study examined the role of intraoperative vasopressors, specifically norepinephrine, in free flap partial necrosis based on the patients’ comorbidities. We retrospectively analyzed 192 patients who received free flap treatment between 2006 and 2021 and were stratified based on vascular comorbidities. We assessed the role of intraoperative vasopressors using multivariate analysis. Patients who were administered vasopressors did not have a significantly higher risk of partial flap necrosis compared to patients who were not administered vasopressors (OR: 1.439, 95% CI: 0.618-3.348, p=0.399). Upon stratifying by vascular comorbidities, we found that patients with two or more vascular comorbidities who were administered vasopressors had a significantly higher risk of developing flap necrosis (OR: 3.882, 95% CI: 1.266-14.752, p=0.046), indicating that vasopressor use in patients with multiple vascular comorbidities is a risk factor for partial flap necrosis. To minimize the risk of flap marginal necrosis in patients with vascular comorbidities, we recommend limited use of vasopressors or minimizing the flap area to preserve vascularization.

Introduction: Clinical practice demands understanding the complexity of the root canal system to achieve desired treatment goals. The statistically detailed morphology of the tooth and root canal morphology is very important to know. Therefore, the present study aims to investigate the statistical analysis of root canal morphology and morphological variations of maxillary and mandibular incisor teeth using cone-beam computed tomography (CBCT) in Saudi patients attending King Saud University Dental Hospital. Materials and Methods: CBCT images of 480 patients were selected. Number of roots and root canal configuration were identified and categorized according to Vertucci’s classification. Tooth length, distance from cementoenamel junction (CEJ) to the area of canal division, and width of the canal at the area of division were also evaluated. Bilateral symmetry and association between gender and age with the different variables were investigated. Data were analyzed using Chi-square, multiple linear regression, and McNemar’s tests. Results: A total of 3412 teeth were evaluated. All maxillary teeth had one root with Type I canal configuration. For mandibular teeth, all exhibited one root with the majority having Type I canal configuration in central (71.2%) and lateral (75%) incisor teeth. There was a statistically significant association between number of canals and age in mandibular incisor teeth observed only in females (P < 0.001), while no association was observed between canal configuration and gender (P = 0.900 and P = 0.721, respectively). Multiple regression analyses showed that age and gender significantly explain the difference of the variance in tooth length (P < 0.001). Moreover, bilateral symmetry was observed in 98.1% of mandibular central and 97.6% of lateral incisor teeth with no statistically significant association (P = 1 and P = 0.058, respectively). Conclusion: All maxillary and most mandibular incisor teeth present with one root and Type I canal configuration. In general, males have longer teeth than females, with a significant decrease in length with each year increase in age. Mandibular lateral incisor teeth exhibited the highest mean distance from CEJ to point of canal separation and highest mean width in the area of canal division.

The treatment of severe burn injuries, which occur particularly in the context of armed conflicts, is based on a multimodal treatment concept. In addition to complex intensive care therapy, the surgical reconstruction options of plastic surgery and typical antiseptic wound treatment are the main focuses. In recent years, atmospheric cold plasma therapy (ACPT) has also become established for topical, antiseptic wound treatment and for the optimization of re-epithelialization. This case report shows a successful treatment of extensive burn injuries using dermal skin substitute matrix and topical treatment with a large-area cold plasma device to control multi-resistant pathogen colonization. This case report illustrates the importance of ACPT in burn surgery. However, larger case series and randomized controlled trials in specialized centers are needed to assess its place in future clinical practice.

Abstract Background Menstruation is a normal biological process experienced by more than 300 million women globally every day. Women require clean menstrual absorbents that can be changed as often as needed in a private and safe place with proper hygiene and disposal facilities. These needs must be met consistently throughout the duration of the menstrual cycle. Access to menstrual needs is crucial for women’s health, wellbeing, and dignity. This study assessed the prevalence and factors associated with unmet need for menstrual hygiene management (MHM) in Ethiopia, Kenya, Uganda, Burkina Faso, Ghana, and Niger. Methods We used data from the Performance Monitoring for Action (PMA) 2020 surveys. We defined the unmet need for MHM as the “lack of resources, facilities and supplies for MHM.” Sample characteristics were summarised using frequencies and percentages, while prevalence was summarised using proportions and their respective confidence intervals (CI). Factors associated with unmet need for MHM were assessed using multilevel logistic regression models. Results The study included 18,048 women of reproductive age from the six countries. The prevalence of unmet need for MHM was highest in Burkina Faso (74.8%), followed by Ethiopia (69.9%), Uganda (65.2%), Niger (57.8%), Kenya (53.5%), and lowest in Ghana (34.2%). Unmet need for MHM was consistently higher among uneducated and multiparous women, those who reused MHM materials, practiced open defecation, and lived in rural areas across all six countries. The odds of unmet need for MHM were higher among younger women under 35 years, unmarried women, those with lower education levels, and those from poorer households. Similarly, the reuse of MHM materials, use of shared or non-improved toilet facilities, and open defecation increased the odds of unmet need for MHM. In contrast, the presence of handwashing facilities reduced the odds of unmet need for MHM. Conclusion More than half of the women in five of the six countries have an unmet need for MHM, with significantly higher odds among younger women, those with low wealth status, the unmarried, and those with inadequate access to sanitary facilities. This study highlights the state of period poverty in Sub-Saharan Africa. Efforts to end period poverty should consider MHM needs as an integrated whole, as addressing each need in isolation is insufficient.

Abstract Predicting heavy precipitation remains scientifically challenging. Here we combine Atmospheric Infrared Sounder (AIRS) temperature and moisture soundings and weather forecast winds to predict the formation of thermodynamic conditions favourable for convection in the hours following satellite overpasses. Here we treat AIRS retrievals as air parcels that are moved adiabatically to generate time-varying fields. Over much of the Central-Eastern Continental U.S. during the non-winter months of 2019–2020, our derived convective available potential energy alone predicts intense precipitation. For hourly precipitation above the all-hours 99.9th percentile, performance is marginally lower than forecasts from a convection permitting model, but similar to the ERA5 reanalysis and substantially better than using the original AIRS soundings. Our results illustrate how mesoscale advection is a major contributor to developing heavy precipitation in the region. Enhancing the full AIRS record as described here would provide an alternative approach to quantify multi-decade trends in heavy precipitation risk.

Keratins 6, 16, and 17 occupy unique positions within the keratin family. These proteins are not commonly found in the healthy, intact epidermis, but their expression increases in response to damage, inflammation, and hereditary skin conditions, as well as cancerous cell transformations and tumor growth. As a result, there is an active investigation into the potential use of these proteins as biomarkers for different pathologies. Recent studies have revealed the role of these keratins in regulating keratinocyte migration, proliferation, and growth, and more recently, their nuclear functions, including their role in maintaining nuclear structure and responding to DNA damage, have also been identified. This review aims to summarize the latest research on keratins 6, 16, and 17, their regulation in the epidermis, and their potential use as biomarkers in various skin conditions.

Abstract Background Whole-genome sequencing (WGS)-based prediction of drug resistance in Mycobacterium tuberculosis has the potential to guide clinical decisions in the design of optimal treatment regimens. Methods We utilized WGS to investigate drug resistance mutations in a 32-year-old Tanzanian male admitted to Kibong’oto Infectious Diseases Hospital with a history of interrupted multidrug-resistant tuberculosis treatment for more than three years. Before admission, he received various all-oral bedaquiline-based multidrug-resistant tuberculosis treatment regimens with unfavourable outcomes. Results Drug susceptibility testing of serial M. tuberculosis isolates using Mycobacterium Growth Incubator Tubes culture and WGS revealed resistance to first-line anti-TB drugs, bedaquiline, and fluoroquinolones but susceptibility to linezolid, clofazimine, and delamanid. WGS of serial cultured isolates revealed that the Beijing (Lineage 2.2.2) strain was resistant to bedaquiline, with mutations in the mmpR5 gene (Rv0678. This study also revealed the emergence of two distinct subpopulations of bedaquiline-resistant tuberculosis strains with Asp47f and Glu49fs frameshift mutations in the mmpR5 gene, which might be the underlying cause of prolonged resistance. An individualized regimen comprising bedaquiline, delamanid, pyrazinamide, ethionamide, and para-aminosalicylic acid was designed. The patient was discharged home at month 8 and is currently in the ninth month of treatment. He reported no cough, chest pain, fever, or chest tightness but still experienced numbness in his lower limbs. Conclusion We propose the incorporation of WGS in the diagnostic framework for the optimal management of patients with drug-resistant and extensively drug-resistant tuberculosis.

Abstract Background Severe fatigue is a common symptom for people with visual impairment, with a detrimental effect on emotional functioning, cognition, work capacity and activities of daily living. A previous study found that depression was one of the most important determinants of fatigue, but less is known about disease-specific factors in this patient population. This study aimed to explore the association between visual impairment severity and fatigue in adults with low vision, both directly and indirectly, with vision-specific factors and depression as potential mediators. Methods Cross-sectional data were collected from 220 Dutch low vision service patients by telephone interviews. Fatigue was defined as a latent variable by severity and impact on daily life. Potential mediators included vision-related symptoms, adaptation to vision loss and depression. Hypothesized structural equation models were constructed in Mplus to test (in)direct effects of visual impairment severity (mild/moderate, severe, blindness) on fatigue through above mentioned variables. Results The final model explained 60% of fatigue variance and revealed a significant total effect of visual impairment severity on fatigue. Patients with severe visual impairment (reference group) had significantly higher fatigue symptoms compared to those with mild/moderate visual impairment (β = -0.50, 95% bias-corrected confidence interval [BC CI] [-0.86, -0.16]) and those with blindness (β = -0.44, 95% BC CI [-0.80, -0.07]). Eye strain & light disturbance, depression and vision-related mobility mediated the fatigue difference between the severe and mild/moderate visual impairment categories. The fatigue difference between the severe visual impairment and blindness categories was solely explained by eye strain & light disturbance. Moreover, depressive symptoms (β = 0.65, p

Abstract A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. Drug-free and captopril-loaded hydrogels demonstrated excellent product stability and sterility. Rheology testing confirmed sol properties with low viscosity at ambient temperature and increased viscosity and gelation at 37 °C. Captopril-loaded hydrogels significantly inhibited Ang II production in comparison to drug-free hydrogels. DPN mice treated with captopril-loaded hydrogels displayed normalized mechanical sensitivity and reduced inflammation, without side-effects associated with systemic exposure. Our data demonstrate the feasibility of repurposing ACE inhibitors as locally delivered anti-inflammatories for the treatment of sensory deficits in DPN. To the best of our knowledge, this is the first example of a locally delivered ACE inhibitor for the treatment of DPN.

Abstract Aesthetic preference is intricately linked to learning and creativity. Previous studies have largely examined the perception of novelty in terms of pleasantness and the generation of novelty via creativity separately. The current study examines the connection between perception and generation of novelty in music; specifically, we investigated how pleasantness judgements and brain responses to musical notes of varying probability (estimated by a computational model of auditory expectation) are linked to learning and creativity. To facilitate learning de novo, 40 non-musicians were trained on an unfamiliar artificial music grammar. After learning, participants evaluated the pleasantness of the final notes of melodies, which varied in probability, while their EEG was recorded. They also composed their own musical pieces using the learned grammar which were subsequently assessed by experts. As expected, there was an inverted U-shaped relationship between liking and probability: participants were more likely to rate the notes with intermediate probabilities as pleasant. Further, intermediate probability notes elicited larger N100 and P200 at posterior and frontal sites, respectively, associated with prediction error processing. Crucially, individuals who produced less creative compositions preferred higher probability notes, whereas individuals who composed more creative pieces preferred notes with intermediate probability. Finally, evoked brain responses to note probability were relatively independent of learning and creativity, suggesting that these higher-level processes are not mediated by brain responses related to performance monitoring. Overall, our findings shed light on the relationship between perception and generation of novelty, offering new insights into aesthetic preference and its neural correlates.

Abstract Glassy solids evolve towards lower-energy structural states by physical aging. This can be characterized by structural relaxation times, the assessment of which is essential for understanding the glass’ time-dependent property changes. Conducted over short times, a continuous increase of relaxation times with time is seen, suggesting a time-dependent dissipative transport mechanism. By focusing on micro-structural rearrangements at the atomic-scale, we demonstrate the emergence of sub-diffusive anomalous transport and therefore temporal fractional diffusion in a metallic glass, which we track via coherent x-ray scattering conducted over more than 300,000 s. At the longest probed decorrelation times, a transition from classical stretched exponential to a power-law behavior occurs, which in concert with atomistic simulations reveals collective and intermittent atomic motion. Our observations give a physical basis for classical stretched exponential relaxation behavior, uncover a new power-law governed collective transport regime for metallic glasses at long and practically relevant time-scales, and demonstrate a rich and highly non-monotonous aging response in a glassy solid, thereby challenging the common framework of homogeneous aging and atomic scale diffusion.

Objective To explore in a primary care setting the associations between patients’ daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately.Design and setting The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden.Patients Participants (n = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate.Main outcome measures Association between self-reported BP and 10 self-report lifestyle-related variables.Results Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP (p

Abstract Background Oesophageal cancer surgery represents a high perioperative risk of complications to patients, such as postoperative pulmonary complications (PPCs). Postoperative analgesia may influence these risks, but the most favourable analgesic technique is debated. This review aims to provide an updated evaluation of whether thoracic epidural analgesia (TEA) has benefits compared to other analgesic techniques in patients undergoing oesophagectomy surgery. Our hypothesis is that TEA reduces pain scores and PPCs compared to intravenous opioid analgesia in patients post-oesophagectomy. Methods Electronic databases PubMed, Excerpta Medica Database (EMBASE) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomised trials of analgesic interventions in patients undergoing oesophagectomy surgery. Only trials including thoracic epidural analgesia compared with other analgesic techniques were included. The primary outcome was a composite of respiratory infection, atelectasis and respiratory failure (PPCs), with pain scores at rest and on movement as secondary outcomes. Data was pooled using random effect models and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CIs). Results Data from a total of 741 patients in 10 randomised controlled trials (RCTs) from 1993 to 2023 were included. Nine trials were open surgery, and one trial was laparoscopic. Relative to intravenous opioids, TEA significantly reduced a composite of PPCs (risk ratio (RR) 3.88; 95% confidence interval (CI) 1.98–7.61; n = 222; 3 RCTs) and pain scores (0–100-mm visual analogue scale or VAS) at rest at 24 h (MD 9.02; 95% CI 5.88–12.17; n = 685; 10 RCTs) and 48 h (MD 8.64; 95% CI 5.91–11.37; n = 685; 10 RCTs) and pain scores on movement at 24 h (MD 14.96; 95% CI 5.46–24.46; n = 275; 4 RCTs) and 48 h (MD 16.60; 95% CI 8.72–24.47; n = 275; 4 RCTs). Conclusions Recent trials of analgesic technique in oesophagectomy surgery are restricted by small sample size and variation of outcome measurement. Despite these limitations, current evidence indicates that thoracic epidural analgesia reduces the risk of PPCs and severe pain, compared to intravenous opioids in patients following oesophageal cancer surgery. Future research should include minimally invasive surgery, non-epidural regional techniques and record morbidity, using core outcome measures with standardised endpoints. Trial registration Prospectively registered on PROSPERO (CRD42023484720).

Abstract Background Since the antisense oligonucleotide tofersen has recently become available for the treatment of amyotrophic lateral sclerosis (ALS) caused by mutations in SOD1, determining the causality of the over 230 SOD1 variants has become even more important. The most common SOD1 variant worldwide is p.D91A (c.272A > C), whose causality for ALS is contested when in a heterozygous state. The reason is the high allele frequency of SOD1 D91A in Europe, exceeding 1% in Finno-Scandinavia. Methods We present the clinical disease course and serum neurofilament light chain (NfL) results of treating 11 patients either homo- or heterozygous for the SOD1 D91A allele for up to 16 months with tofersen. Results Tofersen decreases serum neurofilament levels (sNFL), which are associated with the ALS progression rate, in the 6 ALS patients homozygous for SOD1 D91A . We observe significantly lower sNfL levels in the 5 patients heterozygous for SOD1 D91A . The results indicate that both mono- and bi-allelic SOD1 D91A are causally relevant targets, with a possibly reduced effect size of SOD1 D91Ahet . Conclusions The finding is relevant for decision making regarding tofersen treatment, patient counseling and inclusion of SOD1 D91A patients in drug trials. As far as we are aware, the approach is conceptually new since it provides evidence for the causality of an ALS variant based on a biomarker response to gene-specific treatment.

Abstract Background As a nexus of routine antibiotic use and zoonotic pathogen presence, the livestock farming environment is a potential hotspot for the emergence of zoonotic diseases and antibiotic resistant bacteria. Livestock can further facilitate disease transmission by serving as intermediary hosts for pathogens before a spillover event. In light of this, we aimed to characterize the microbiomes and resistomes of dairy workers, whose exposure to the livestock farming environment places them at risk for facilitating community transmission of antibiotic resistant genes and emerging zoonotic diseases. Results Using shotgun sequencing, we investigated differences in the taxonomy, diversity and gene presence of 10 dairy farm workers and 6 community controls’ gut metagenomes, contextualizing these samples with additional publicly available gut metagenomes. We found no significant differences in the prevalence of resistance genes, virulence factors, or taxonomic composition between the two groups. The lack of statistical significance may be attributed, in part, to the limited sample size of our study or the potential similarities in exposures between the dairy workers and community controls. We did, however, observe patterns warranting further investigation including greater abundance of tetracycline resistance genes and prevalence of cephamycin resistance genes as well as lower average gene diversity (even after accounting for differential sequencing depth) in dairy workers’ metagenomes. We also found evidence of commensal organism association with tetracycline resistance genes in both groups (including Faecalibacterium prausnitzii, Ligilactobacillus animalis, and Simiaoa sunii). Conclusions This study highlights the utility of shotgun metagenomics in examining the microbiomes and resistomes of livestock workers, focusing on a cohort of dairy workers in the United States. While our study revealed no statistically significant differences between groups in taxonomy, diversity and gene presence, we observed patterns in antibiotic resistance gene abundance and prevalence that align with findings from previous studies of livestock workers in China and Europe. Our results lay the groundwork for future research involving larger cohorts of dairy and non-dairy workers to better understand the impact of occupational exposure to livestock farming on the microbiomes and resistomes of workers.

Abstract Commensal relationships between wild plants and their dispersers play a key ecological and evolutionary role in community structure and function. While non-human dispersers are often considered critical to plant recruitment, human dispersers have received much less attention, especially when it comes to non-domesticated plants. Australia, as a continent historically characterized by economies reliant on non-domesticated plants, is thus a key system for exploring the ecological role of people as seed dispersers in the absence of agriculture. Here, we utilize a controlled observation research design, employing ecological surveys and ethnographic observations to examine how seed dispersal and landscape burning by Martu Aboriginal people affects the distribution of three preferred plants and one (edible, but non-preferred) control species. Using an information theoretic approach, we find that the three preferred plants show evidence of human dispersal, with the strongest evidence supporting anthropogenic dispersal for the wild bush tomato, Solanum diversiflorum.

Abstract Objective Neurofilament heavy‐chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. Methods Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta‐analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole‐genome sequencing data. Results Fixed‐effects meta‐analysis found that rare (MAF

Abstract The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06–1.48]), with HRCAs (0.38 [0.14–1.01]), and with gain/amp(1q21) (0.42 [0.14–1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35–1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM. Video Abstract

Abstract The costs and benefits of group living are also reflected in intraspecific variation in group size. Yet, little is known about general patterns of fitness consequences of this variation. We use demographic records collected over 25 years to determine how survival and reproductive success vary with group size in a Malagasy primate. We show that female reproductive rates of Verreaux’s sifakas (Propithecus verreauxi) are not affected by total group size, but that they are supressed by the number of co-resident females, whereas mortality rates are significantly higher in larger groups. Neither annual rainfall nor the adult sex ratio have significant effects on birth and death rates. Hence, these sifakas enjoy the greatest net fitness benefits at small, and not the predicted intermediate group sizes. Thus, independent fitness proxies can vary independently as a function of group size as well as other factors, leading to deviations from optimal intermediate group sizes.

Abstract Background Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions. Results The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3–20.8) years. When examining independent effects, APOE ε4 genotype(p

Abstract Introduction Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called “Adappt,” aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences. Method A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with “Adappt.” Discussion Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care. Trial registration This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).

Fusarium oxysporum f. sp. fragariae (Fof) race 1 is avirulent on cultivars with the dominant resistance gene FW1, while Fof race 2 is virulent on FW1-resistant cultivars. We hypothesized there was a gene-for-gene interaction between a gene at the FW1 locus and an avirulence gene (AvrFW1) in Fof race 1. To identify a candidate AvrFW1, we compared genomes of 24 Fof race 1 and three Fof race 2 isolates. We found one candidate gene that was present in race 1, was absent in race 2, was highly expressed in planta, and was homologous to a known effector, secreted in xylem 6 (SIX6). We knocked out SIX6 in two Fof race 1 isolates by homologous recombination. All SIX6 knockout transformants (ΔSIX6) gained virulence on FW1/fw1 cultivars, whereas ectopic transformants and the wildtype isolates remained avirulent. ΔSIX6 isolates were quantitatively less virulent on FW1/fw1 cultivars Fronteras and San Andreas than fw1/fw1 cultivars. Seedlings from an FW1/fw1 × fw1/fw1 population were genotyped for FW1 and tested for susceptibility to a SIX6 knockout isolate. Results suggested that additional minor-effect quantitative resistance genes could be present at the FW1 locus. This work demonstrates that SIX6 acts as an avirulence factor interacting with a resistance gene at the FW1 locus. The identification of AvrFW1 enables surveillance for Fof race 2 and provides insight into the mechanisms of FW1-mediated resistance. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Marine sediments in glacially-carved fjords at high latitudes feature high organic carbon (OC) burial rates, but there are fewer data on the role of glacial activity on high-latitude OC burial rates outside of fjords. Here, we investigate the relationship between sediment OC burial rates in the deep troughs and basins of the southwest Greenland shelf and Holocene glacial dynamics. Since the onset of prominent Neoglacial advances ~2500 years ago, the nature of the OC buried in the deep troughs and basins of the shelf was influenced by the glacier-driven increase in sediment accumulation rates (SAR), reactive iron (oxyhydr)oxide concentrations and fine-grain sediment, while OC burial rates were primarily enhanced by increasing SAR. Peak OC burial rates (~18.5 ± 5.7 g m−2 a−1) in the deep troughs and basins of the shelf during the past ~1300 years are comparable to those of many high-latitude fjords, and the inferred total annual OC burial in these trough and basin areas is equivalent to ~5% of the annual CO2 uptake by the Labrador Sea deep convection.

A listening experiment was designed to test whether modern listeners perceive the same affective content in Baroque music as the composer intended to portray. Listeners rated three musical examples from Johann David Heinichen’s 1728 treatise Der General-Bass in der Composition for valence and arousal. Examples were chosen based on descriptions by the composer in which he outlined their intended affective content. Results showed a significant mismatch between original descriptions and listener ratings, indicating a change in the perceived affective content of the music. The historical variability of musical-emotional expression in general, with a focus on the role of structural emotion cues (particularly mode), is discussed, closing with suggestions for future research in the area of historical musical emotion

Abstract Introduction Hand injuries constitute up to 30% of the total cases treated in emergency departments. Over time, demographic changes, especially an aging population, and shifts in workplace safety regulations and healthcare policies have significantly impacted the landscape of hand trauma. This study aims to identify and analyze these evolving trends over nearly two decades. Methods In this retrospective, cross-sectional study, we investigated patients who were admitted to the high-volume regional hand trauma center of a university hospital between January 2007 and December 2022. We analyzed trends in patients’ demographics and annual alterations of injuries. For the comparative analysis, patients were divided into two groups based on the time of presentation: the early cohort (2007–2014) and the current cohort (2015–2022). Results A total of 14,414 patients were admitted to our emergency department within the study period. A significant annual increase in patient age was identified (R2 = 0.254, p = 0.047). The number of presentations increased annually by an average of 2% (p

Abstract Coherent light-matter interactions mediated by opto-magnetic phenomena like the inverse Faraday effect (IFE) are expected to provide a non-thermal pathway for ultrafast manipulation of magnetism on timescales as short as the excitation pulse itself. As the IFE scales with the spin-orbit coupling strength of the involved electronic states, photo-exciting the strongly spin-orbit coupled core-level electrons in magnetic materials appears as an appealing method to transiently generate large opto-magnetic moments. Here, we investigate this scenario in a ferrimagnetic GdFeCo alloy by using intense and circularly polarized pulses of extreme ultraviolet radiation. Our results reveal ultrafast and strong helicity-dependent magnetic effects which are in line with the characteristic fingerprints of an IFE, corroborated by ab initio opto-magnetic IFE theory and atomistic spin dynamics simulations.

Abstract Background Research on cannabis use motives has focused on youth. Little is known about motives among working adults, including how work may play a role. This study aimed to describe cannabis use motives and their connection to work, and identify the personal and work correlates of work-related motives among a sample of workers. Methods A national, cross-sectional sample of Canadian workers were queried about their cannabis use. Workers reporting past-year cannabis use (n = 589) were asked their motives for using cannabis and whether each motive was related to work or helped them manage at work (i.e., work-related). Multinomial logistic regression analyses were conducted to estimate the associations of personal and work characteristics with work-related cannabis use motives (no work-related motives,