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Transportation networks play a crucial role in society by enabling the smooth movement of people and goods during regular times and acting as arteries for evacuations during catastrophes and natural disasters. Identifying the critical road segments in a large and complex network is essential for planners and emergency managers to enhance the networks efficiency, robustness, and resilience to such stressors. We propose a novel approach to rapidly identify critical and vital network components (road segments in a transportation network) for resilience improvement or post-disaster recovery. We pose the transportation network as a graph with roads as edges and intersections as nodes and deploy a Graph Neural Network (GNN) trained on a broad range of network parameter changes and disruption events to rank the importance of road segments. The trained GNN model can rapidly estimate the criticality rank of individual road segments in the modified network resulting from an interruption. We address two main limitations in the existing literature that can arise in capital planning or during emergencies: ranking a complete network after changes to components and addressing situations in post-disaster recovery sequencing where some critical segments cannot be recovered. Importantly, our approach overcomes the computational overhead associated with the repeated calculation of network performance metrics, which can limit its use in large networks. To highlight scenarios where our method can prove beneficial, we present examples of synthetic graphs and two real-world transportation networks. Through these examples, we show how our method can support planners and emergency managers in undertaking rapid decisions for planning infrastructure hardening measures in large networks or during emergencies, which otherwise would require repeated ranking calculations for the entire network.

BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (

Triple negative breast cancers often contain higher numbers of tumour-infiltrating lymphocytes compared with other breast cancer subtypes, with their number correlating with prolonged survival. Since little is known about tumour-infiltrating lymphocyte trafficking in triple negative breast cancers, we investigated the relationship between tumour-infiltrating lymphocytes and the vascular compartment to better understand the immune tumour microenvironment in this aggressive cancer type. We aimed to identify mechanisms and signaling pathways responsible for immune cell trafficking in triple negative breast cancers, specifically of basal type, that could potentially be manipulated to change such tumours from immune "cold" to "hot" thereby increasing the likelihood of successful immunotherapy in this challenging patient population. We characterised the spatial immune environment in 10 basal breast cancers showing a range of tumour-infiltrating lymphocytes using multiplex fluorescent immunohistochemistry and quantitative digital analysis of CD3+ T cells. We examined their relationship to blood vessels and their activation status as defined by VCAM-1, ICAM-1 and PD-L1. Confirmation of the relationship between tumour-infiltrating lymphocytes and endothelial activation was performed through in silico analysis on TCGA BRCA RNA-seq data (N = 808). Significantly higher CD3+ T cell densities were observed in the stromal compartment compared with the neoplastic cell compartment (P = 0.003). ICAM-1 activated blood vessels were spatially associated with higher CD3+ T cell densities only within 30 microns of blood vessels compared with more distal activated and non-activated blood vessels (P = 0.041). In silico analysis confirmed higher numbers of tumour-infiltrating lymphocytes in basal breast cancers and that higher numbers were significantly associated with endothelial cell activation molecules, co-clustering with upregulated ICAM-1 and VCAM-1 amongst others. PD-L1 was also identified in a subset of blood vessels, suggesting an additional immune regulatory mechanism in endothelial cells. Regulating the activation status of tumour-associated vascular endothelial cells may improve T cell trafficking into basal breast tumours and enhance immunotherapeutic response. [ABSTRACT FROM AUTHOR]

Introduction: Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background of RCC in native kidneys has been determined, implicating its clinical importance. Materials and methods: This retrospective single-center pilot study aimed to identify a potential genetic predisposition to RCC of the transplanted kidney and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested RCC of the transplanted kidney. Next-generation sequencing (NGS) based germline genetic analysis from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using a gene panel targeting 226 cancer predisposition genes. Results: The calculated incidence of RCC of the transplanted kidney among 4146 KTR was 0.43%. In fifteen KTR and donors, NGS was performed. The mean KTR age at transplantation and the diagnosis of RCC was 50.3 years (median 54; 5–67 years) and 66 years (median 66; 24–79 years), respectively. The mean donor age at transplantation and graft age at RCC diagnosis was 39.7 years (median 42; 7–68 years) and 50.2 years (median 46; 20–83 years), respectively. The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0–112 months). Papillary RCC was the most prevalent (n = 8), followed by clear cell RCC (n = 6) and unspecified RCC (n = 1). Thirteen RCCs were low-stage (pT1a/b) diseases, one was pT3, and one was of unknown stage. Most RCC was higher graded. No germline pathogenic cancer-predisposition variant was found in either KTR or donors except for several variants of uncertain significance. Conclusion: RCC of the transplanted kidney is very rare. Germline cancer-predisposition testing has identified several variants of uncertain significance, but no germline genetic predisposition to graft RCC in KTR. Further research is needed to assess the clinical relevance of genetic testing for cancer risk in KTR. [ABSTRACT FROM AUTHOR]

University students are at a pivotal stage of shaping cancer risk factors. Little is known about their dietary behavior in Lebanon, a country heavily burdened by cancer. This cross-sectional study assessed the dietary knowledge of and adherence to cancer prevention guidelines among university students in Beirut, Lebanon. We hypothesized that students would exhibit low knowledge, poor diet quality, and that knowledge predicted diet quality. Dietary knowledge was explored using a dedicated questionnaire, with scores above the 60th percentile considered as Knowledgeable (Kn+), and those below as less knowledgeable (Kn-). Dietary adherence to cancer prevention guidelines and the predictors of the Alternative Healthy Eating Index (AHEI)- a measure of diet quality calculated using the Modified Mediterranean Prime Screen, were also examined. The sample included 300 participants (55% females, mean age: 20 years). The mean knowledge score was 49.5%. Over 50% of students were aware of the association between red and processed meat, sodium, fruits and vegetables, obesity, and cancer. Kn+ group had a higher intake of vegetables and a lower intake of meats and sweetened beverages. Increased knowledge (B = 0.78, 95%CI: 0.18,1.37) and high physical activity (B = 4.62, 95%CI: 1.66,7.59) were associated with elevated AHEI scores. A significant positive interaction was observed between knowledge and enrollment in a health-related major. University students' dietary knowledge of and adherence to cancer prevention guidelines are suboptimal. Although higher knowledge predicts high-quality diets, the association was weak. Further studies should investigate the food systems influencing university students' dietary intake of university students in Lebanon and identify effective interventions to enhance health behavior. [ABSTRACT FROM AUTHOR]

Background: Although a lot of attention is paid to the flaws of balance training research in older adults, the low methodological quality and incomplete reporting of studies still limit the knowledge transfer between research and practice. These known shortcomings are considered also as barriers for creating recommendations for balance training in older adults. Despite the considerable efforts to improve the scientific quality of studies, such recommendations have not yet been formulated to date. Therefore, this scoping review aims (1) to analyze the literature that addresses balance training in older adults, (2) to identify and summarize gaps in the existing literature, and (3) to propose future research on this topic. Methods: We focused on studies that evaluated the effect of balance training on balance control in apparently healthy older adults over 60 years of age. Results: Out of 6910 potentially relevant studies, only 26 met the eligibility criteria. The identified shortcomings were as follows: missing a priori criteria for training session attendance and leisure-time physical activities, insufficiently described exercises and training load, and inappropriately chosen tests. Conclusions: Among the shortcomings of the balance training research, the insufficiently described balance training program and inappropriately chosen tests can be considered the most important. For this reason, even with an excellently designed experiment, it is almost impossible for practitioners to apply the results of such studies into practice. Therefore, researchers should pay more attention to possible users of the acquired knowledge, which is more than desirable in the case of exercise programs for older adults. [ABSTRACT FROM AUTHOR]

Introduction: The aging process is intricately linked to alterations in cellular and tissue structures, with the respiratory system being particularly susceptible to age-related changes. Therefore, this study aimed to profile the activity of proteases using activity-based probes in lung tissues of old and young rats, focusing on the expression levels of different, in particular cathepsins G and X and matrix Metalloproteinases (MMPs). Additionally, the impact on extracellular matrix (ECM) components, particularly fibronectin, in relation to age-related histological and ultrastructural changes in lung tissues was investigated. Materials and methods: Lung tissues from old and young rats were subjected to activity-based probe profiling to assess the activity of different proteases. Expression levels of cathepsins G and X were quantified, and zymography was performed to evaluate matrix metalloproteinases activity. Furthermore, ECM components, specifically fibronectin, were examined for signs of degradation in the old lung tissues compared to the young ones. Moreover, histological, immunohistochemical and ultrastructural assessments of old and young lung tissue were also conducted. Results: Our results showed that the expression levels of cathepsins G and X were notably higher in old rat lung tissues in contrast to those in young rat lung tissues. Zymography analysis revealed elevated MMP activity in the old lung tissues compared to the young ones. Particularly, significant degradation of fibronectin, an essential ECM component, was observed in the old lung tissues. Numerous histological and ultrastructural alterations were observed in old lung tissues compared to young lung tissues. Discussion and conclusion: The findings indicate an age-related upregulation of cathepsins G and X along with heightened MMP activity in old rat lung tissues, potentially contributing to the degradation of fibronectin within the ECM. These alterations highlight potential mechanisms underlying age-associated changes in lung tissue integrity and provide insights into protease-mediated ECM remodeling in the context of aging lungs. [ABSTRACT FROM AUTHOR]

Purpose: The current research analyzes cosmetic earnings management practices in emerging and developed markets before and after the global financial crisis. Design/Methodology/Approach: Using digital analysis, by applying Benford's Law the study analyzes the earnings adjustments that exceed a key reference point to determine whether earnings management anomaly exists or not? Based on a sample of 87165 firm-year observations of UK, US, Brazil, Russia, India, China and Pakistan listed corporations. Findings: Findings show that the managers of emerging markets have more incentive to manipulate earnings than their counterparts from developed markets. Further, the implementation of strict governance and legislative measures after the global financial crisis have significantly reduced the opportunistic behaviour of managers to manipulate earnings. However, the impact is lesser in emerging markets as compared to UK and US. Research implications: The empirical findings of this research are useful for policy making and regulatory authorities, investors and other stakeholders as our findings shed light on the restriction of cosmetic earnings management practices. Originality/Value: First study that tried to capture the cosmetic earnings management practices in both emerging and developed countries and in both pre and post financial crisis scenario. [ABSTRACT FROM AUTHOR]

Background: Researchers have increasingly recognized the importance of structural and social determinants of health (SSDOH) as key drivers of a multitude of diseases and health outcomes. The Multi-Ethnic Study of Atherosclerosis (MESA) is an ongoing, longitudinal cohort study of subclinical cardiovascular disease (CVD) that has followed geographically and racially/ethnically diverse participants starting in 2000. Since its inception, MESA has incorporated numerous SSDOH assessments and instruments to study in relation to CVD and aging outcomes. In this paper, we describe the SSDOH data available in MESA, systematically review published papers using MESA that were focused on SSDOH and provide a roadmap for future SSDOH-related studies. Methods and findings: The study team reviewed all published papers using MESA data (n = 2,125) through January 23, 2023. Two individuals systematically reviewed titles, abstracts, and full text to determine the final number of papers (n = 431) that focused on at least one SSDOH variable as an exposure, outcome, or stratifying/effect modifier variable of main interest (discrepancies resolved by a third individual). Fifty-seven percent of the papers focused on racialized/ethnic groups or other macrosocial/structural factors (e.g., segregation), 16% focused on individual-level inequalities (e.g. income), 14% focused on the built environment (e.g., walking destinations), 10% focused on social context (e.g., neighborhood socioeconomic status), 34% focused on stressors (e.g., discrimination, air pollution), and 4% focused on social support/integration (e.g., social participation). Forty-seven (11%) of the papers combined MESA with other cohorts for cross-cohort comparisons and replication/validation (e.g., validating algorithms). Conclusions: Overall, MESA has made significant contributions to the field and the published literature, with 20% of its published papers focused on SSDOH. Future SSDOH studies using MESA would benefit by using recently added instruments/data (e.g., early life educational quality), linking SSDOH to biomarkers to determine underlying causal mechanisms linking SSDOH to CVD and aging outcomes, and by focusing on intersectionality, understudied SSDOH (i.e., social support, social context), and understudied outcomes in relation to SSDOH (i.e., sleep, respiratory health, cognition/dementia). [ABSTRACT FROM AUTHOR]

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016–2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections–C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84–237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16–13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07–0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions. [ABSTRACT FROM AUTHOR]

Epistemic trust, defined as trust in socially transmitted knowledge, is discussed as a psychopathological factor in the context of new transdiagnostic approaches for the assessment of mental disorders. The aim of this study is to test the factorial, convergent, and discriminant validity of the German version of the new Epistemic Trust, Mistrust and Credulity–Questionnaire (ETMCQ). Data were collected cross-sectionally from the German-speaking general population (N = 584) and in a second sample of clinical (n = 30) and non-clinical (n = 30) participants. The previously proposed three-factor structure of the ETMCQ was analyzed using confirmatory factor analysis. The ETMCQ's ability to differentiate between clinical and non-clinical participants was tested with t-tests. Correlations with early childhood trauma, maladaptive personality traits, and impairments in personality functioning were examined. The relationship between epistemic trust and mentalization was analyzed in a structural equation model. Regarding the factorial validity, the model fit of the originally proposed ETMCQ proved to be insufficient. The model fit to the data was good for a shortened 12-item version. The study was unable to identify any significant differences between clinical and non-clinical participants. For mistrust and credulity, correlations with associated constructs supported their construct validity. However, the results for the trust subscale were heterogeneous. The study offers initial empirical support for a revised 12-item self-report measure of epistemic trust and for the link between mistrust and credulity with markers of psychopathology. Further investigation of the ETMCQ and its psychometric properties, as well as research on integration of epistemic trust into new, transdiagnostic approaches to psychopathology is needed. [ABSTRACT FROM AUTHOR]

Background: The accurate estimation of residual growth is crucial for the appropriate timing of growth-guiding surgery in patients with axial leg deviations. Skeletal age methods such as the Modified and the Abbreviated Modified Fels Knee System were developed on historical patient cohorts and the applicability to the modern pediatric population with axial leg deviation has not yet been evaluated. Questions/purposes: Are both final adult height prediction methods (the Modified Fels Knee System (FKS) and the Abbreviated Modified Fels Knee System (aFKS)) accurate to determine SA and the final adult height on long leg radiographs in patients with axial leg deviations? Which multiplier table shows highest association between predicted and true final adult body height? Do FKS- and aFKS- skeletal age determination methods improve final adult body height prediction accuracy compared to the simple use of chronological age? Methods: A single center, retrospective study of 31 patients who underwent temporary hemiepiphysiodesis due to axial leg deviations in the frontal plane between 2018 and 2020 was conducted. Skeletal age at the time of surgery was determined on an anterior-posterior long leg X-ray using FKS and aFKS. Adult height predictions were calculated using three different multiplier tables (Paley et al., Sanders-Greulich and Pyle (SGP), Sanders-Peak Height Velocity (PHV)). The accuracy of adult height prediction was determined by comparing the mean differences and mean absolute differences between predicted and true adult height. Results: All adult height predictions overestimated the true adult height. The final height prediction using aFKS and the SGP multiplier showed the lowest overestimation (mean 3.2 cm, SD 5.5 cm). The PHV multiplier table showed the highest correlation between predicted and true adult height (FHPRE_FKS_PHV: r = 0.913, p < 0.001 and FHPRE_aFKS_PHV: r = 0.862, p < 0.001). The simple use of chronological age at the time of surgical intervention (CASI) with the Paley multiplier table showed the highest median delta absolute values and lowest correlations with true adult height (median 7.4 cm, 25%-75% percentile: 3.5–10.0 cm, r = 0.838, p < 0.001). Nevertheless, no significant differences in delta absolute values between various adult height predictions methods could be shown. Conclusions: Overall, the results of the present retrospective cohort study show that there was no significant improvement in final height prediction accuracy when using the FKS or the aFKS method compared to the simple use of chronological age. One reason could be that patients with varus/valgus malalignment have specific growth characteristics that are not accounted for in multiplier tables or the FKS and aFKS method. Since there is no significant difference in prediction accuracy between the methods, the choice of method may depend on other factors, such as clinical preference or availability of resources. However, due to the small sample size, the study cannot definitively rule out potential differences between the prediction methods, and larger studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication, social interaction, and repetitive behavior. The declaration of the COVID-19 pandemic in March 2020 resulted in significant changes in daily life due to restrictive measures. This period posed particular challenges for families with children living with autism, given the limitations in medical care and social services. Objective: This study aimed to understand how families with autistic children perceive stress during the pandemic and the coping strategies employed in unexpected situations. Method: A total of 44 families with children with ASD and 300 control families, including 44 control families in a matched subsample, were included in the study. To assess stress and parental coping with COVID-19-related stress, the Responses to Stress Questionnaire (Adult Self-Report RSQ–COVID-19) was utilized. Results: Caregivers of autistic children experienced significantly higher stress levels (p =.027, d = 0.479) during the pandemic, with notable stressors such as limited access to medical care and challenges associated with remote work. Despite expectations, coping strategy differences were not statistically significant. Conclusion: Families and supporters of children with autism naturally encounter various experiences and challenges stemming from their additional needs. Our study's results highlight an accentuation of stress during challenging situations. As these situations may recur in the future, there is a need to design and implement support plans for these families, appropriate intervention programs, and preparations for the utilization of telemedicine tools. [ABSTRACT FROM AUTHOR]

ObjectiveTo address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects.DesignWe optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort.MethodsThis study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort). We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects.ResultsHere, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects.ConclusionSince plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.

People living with HIV/AIDS (PLH) experience high rates of depression and related psychosocial risk factors that vary by gender. This study examines gender differences in depression severity among antiretroviral therapy (ART) patients (n = 362) from a large government ART clinic in Kolkata, India. Hypotheses for multiple linear regression models were guided by an integrated gendered stress process model focusing on variables reflecting social status (age, partner status), stressors (stigma), and resources (income, social support). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS); 22% of the sample reached the cutoff for severe depression, 56% moderate, and 13% mild depression. Compared to men, women reported lower income, education (50% no formal education vs. 20% men), availability of emotional and instrumental support, and were less likely to be married or cohabiting (53% women vs. 72% of men). However, more women had partners who were HIV-positive (78% women vs. 46% men). Overall, depression severity was negatively associated with availability of emotional support and self-distraction coping, and positively associated with internalized HIV/AIDS stigma, availability of instrumental support, and behavioral disengagement coping. Interactions for instrumental support by income and partner status by age varied significantly by gender. Analyses stratified by gender indicated that: 1) Frequently seeking instrumental support from others was protective for men at all income levels, but only for high-income women; and 2) having a partner was protective for men as they aged, but not for women. These results suggest that gender disparities in depression severity are created and maintained by women's lower social status and limited access to resources. The effect of stigma on depression severity did not vary by gender. These findings may inform the tailoring of future interventions to address mental health needs of PLH in India, particularly gender disparities in access to material and social resources for coping with HIV. Trial Registration: ClinicalTrials.gov registration #NCT02118454, registered April 2014.

BackgroundPreventing unintended pregnancy is critical for women living with HIV (WLWH) to safely achieve their reproductive goals. Family planning services should support WLWH at risk of repeat unintended pregnancies. We examined the relationship between unintended pregnancy and subsequent contraception use among WLWH in Uganda.Study designThis was a retrospective analysis of data from a longitudinal cohort of individuals initiating antiretroviral therapy (ART), restricted to women with pregnancy (confirmed via urine β-hcg testing) between 2011-2013. The exposure of interest was intended vs unintended pregnancy, and the outcome was self-report of modern contraceptive use (hormonal methods, intrauterine device, sterilization, and/or consistent condom use) at 12 (range 6-18) months post-partum. A log-binomial model was used to estimate relative risks of modern contraceptive use post-partum based on intent of the index pregnancy, adjusted for age, socioeconomic status, education, relationship and HIV status of pregnancy partner, contraceptive use prior to pregnancy, years since HIV diagnosis, ART regimen, and CD4 cell count.ResultsAmong 455 women, 110 women reported 110 incident pregnancies with report on intent. Women had a baseline median age of 29 years, baseline CD4 count 403 cells/mm3, and were living with HIV for 3.8 years. Fifty pregnancies (45%) were reported as unintended and 60 (55%) as intended. Postpartum, 64% of women with unintended and 51% with intended pregnancy reported modern contraception (p = 0.24). In adjusted models, there was no association between pregnancy intent and post-partum contraception. However, contraceptive use prior to the referent pregnancy was positively associated with post-partum contraceptive use (aRR 1.97 (95% CI 1.12-3.48, p = 0.02), while higher baseline CD4 cell count was associated with lower post-partum contraceptive use (aRR 0.95, 95% CI 0.90-0.99, p = 0.02).ConclusionsAlmost half of incident pregnancies among WLWH in this cohort were unintended. Experiencing an unintended pregnancy was not associated with post-partum contraceptive use. Creative strategies to support contraceptive uptake for birth spacing and prevention of unintended pregnancies in the post-partum period are needed.

Background: Several studies indicate that people who stutter show greater variability in speech movements than people who do not stutter, even when the speech produced is perceptibly fluent. Speaking to the beat of a metronome reliably increases fluency in people who stutter, regardless of the severity of stuttering. Objectives: Here, we aimed to test whether metronome-timed speech reduces articulatory variability. Method: We analysed vocal tract MRI data from 24 people who stutter and 16 controls. Participants repeated sentences with and without a metronome. Midsagittal images of the vocal tract from lips to larynx were reconstructed at 33.3 frames per second. Any utterances containing dysfluencies or non-speech movements (e.g. swallowing) were excluded. For each participant, we measured the variability of movements (coefficient of variation) from the alveolar, palatal and velar regions of the vocal tract. Results: People who stutter had more variability than control speakers when speaking without a metronome, which was then reduced to the same level as controls when speaking with the metronome. The velar region contained more variability than the alveolar and palatal regions, which were similar. Conclusions: These results demonstrate that kinematic variability during perceptibly fluent speech is increased in people who stutter compared with controls when repeating naturalistic sentences without any alteration or disruption to the speech. This extends our previous findings of greater variability in the movements of people who stutter when producing perceptibly fluent nonwords compared with controls. These results also show, that in addition to increasing fluency in people who stutter, metronome-timed speech also reduces articulatory variability to the same level as that seen in control speakers. [ABSTRACT FROM AUTHOR]

The honey bee, Apis mellifera L., is one of the main pollinators worldwide. In a temperate climate, seasonality affects the life span, behavior, physiology, and immunity of honey bees. In consequence, it impacts their interaction with pathogens and parasites. In this study, we used Bayesian statistics and modeling to examine the immune response dynamics of summer and winter honey bee workers after injection with the heat-killed bacteria Serratia marcescens, an opportunistic honey bee pathogen. We investigated the humoral and cellular immune response at the transcriptional and functional levels using qPCR of selected immune genes, antimicrobial activity assay, and flow cytometric analysis of hemocyte concentration. Our data demonstrate increased antimicrobial activity at transcriptional and functional levels in summer and winter workers after injection, with a stronger immune response in winter bees. On the other hand, an increase in hemocyte concentration was observed only in the summer bee population. Our results indicate that the summer population mounts a cellular response when challenged with heat-killed S. marcescens, while winter honey bees predominantly rely on humoral immune reactions. We created a model describing the honey bee immune response dynamics to bacteria-derived components by applying Bayesian statistics to our data. This model can be employed in further research and facilitate the investigating of the honey bee immune system and its response to pathogens. [ABSTRACT FROM AUTHOR]

The structured professional judgement (SPJ) approach was initially developed to support risk assessment and management decisions. The approach is now being adapted and applied to admission assessments for adult secure services. This systematic review aims to summarise the evidence for the effectiveness and acceptability of the SPJ approach in admission assessments of this kind. A comprehensive electronic search strategy was used to identify studies indexed in PubMed, PsycInfo, Medline and Cochrane Library (January 2007 –January 2024). Two search strategies included terms (and synonyms) for psychiatric patients (quantitative) or clinicians and clinicians' experiences (qualitative), structured professional judgement, admission, and secure services. Twelve quantitative articles (published 2007–2020) were identified. SPJ-informed guidance included were the DUNDRUM-1, DUNDRUM-2, DUNDRUM-3, DUNDRUM-4, and the HCR-20. While findings were variable, the overall pattern indicated that ratings suggestive of more problems were associated with increased likelihood of admission or movement to higher security levels. There is emerging evidence for the use of SPJ guidance to support admission decision-making. Specifically, it should be used as an adjunct to existing decision-making processes rather than as a replacement for those processes. Further research, both quantitative and qualitative, across a wider range of settings and populations is recommended. [ABSTRACT FROM AUTHOR]

Identifying causal sentences from nuclear incident reports is essential for advancing nuclear safety research and applications. Nonetheless, accurately locating and labeling causal sentences in text data is challenging, and might benefit from the usage of automated techniques. In this paper, we introduce LERCause, a labeled dataset combined with labeling methods meant to serve as a foundation for the classification of causal sentences in the domain of nuclear safety. We used three BERT models (BERT, BioBERT, and SciBERT) to 10,608 annotated sentences from the Licensee Event Report (LER) corpus for predicting sentence labels (Causal vs. non-Causal). We also used a keyword-based heuristic strategy, three standard machine learning methods (Logistic Regression, Gradient Boosting, and Support Vector Machine), and a deep learning approach (Convolutional Neural Network; CNN) for comparison. We found that the BERT-centric models outperformed all other tested models in terms of all evaluation metrics (accuracy, precision, recall, and F1 score). BioBERT resulted in the highest overall F1 score of 94.49% from the ten-fold cross-validation. Our dataset and coding framework can provide a robust baseline for assessing and comparing new causal sentences extraction techniques. As far as we know, our research breaks new ground by leveraging BERT-centric models for causal sentence classification in the nuclear safety domain and by openly distributing labeled data and code to enable reproducibility in subsequent research. [ABSTRACT FROM AUTHOR]

Introduction: Patients with head and neck cancer (PwHNC) benefit from targeted exercise interventions: symptom relief, compensation for dysfunction, improvement in quality of life (QoL). Data on acceptance physical interventions in PwHNC are rare. The 'OSHO #94' trial investigates the short- and medium-term effects of individualized home exercise in PwHNC on QoL, physical activity and functionality. The study includes a feasibility phase (proof of concept) in order to evaluate the acceptance. Here we present the study protocol as well as the feasibility results. Methods and analysis: This prospective, multicentre, single-arm intervention study includes PwHNC ≥18 years of age in aftercare or palliative care with stable remission under immunotherapy. The study opened in January 01, 2021, with estimated completion by December 31, 2024. The PwHNC receive an individualized home exercise program consisting of mobilization, coordination, strengthening and stretching exercises. This should be carried out at least three times a week over 12 weeks for 15 to 30 minutes, supplemented by aerobic training two to three times a week for 30 minutes (intervention). Once weekly telephone calls with a physiotherapist are performed. Subsequently, there is a 12-week follow-up (FU) without exercise specifications/contact. Outcomes are measured before and after the intervention and following the FU. Primary outcome of the feasibility phase (n = 25) was the determination of the dropout rate during the intervention with a termination cut off if more than 30% PwHNC withdrew premature. The primary outcome of the OSHO #94' trial (N = 53) is the change in global QoL score from pre- to post-intervention (EORTC QLQ-C30). Secondary outcomes include clinical and patient-reported measures, training details as well as functional diagnostic data (e.g. level of physical activity, training frequency, flexibility, fall risk and aerobic performance). Results: 25 PwHNC were enrolled onto the feasibility cohort. Only16% (4/25 patients) did not complete the study. Therefore, recruitment of PwHNC was continued. The dropout rate was adjusted from 30% (N = 60) to 20% (N = 53, calculated sample size n = 42 PwHNC and 20% (n = 11) to dropout). Conclusions: Individualized home exercise programs in PwHNC in aftercare seem feasible. Consequently, the aim is now to evaluate the short and medium-term effects of individualized home exercise. [ABSTRACT FROM AUTHOR]

This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.

Background: Despite accessible diagnostics and treatment of hypertension, a high proportion of patients worldwide remain unaware of their diagnosis, and even more remain untreated. Several studies suggest that absence of comorbidities is a predictive factor for unawareness and consequently non-treatment of hypertension. There are only a few studies that have assessed the hypertension prevalence and management among apparently healthy individuals. Objective: The aim of the study was to assess and compare hypertension prevalence, awareness, treatment and control among apparently healthy individuals, patients with internal diseases, and patients with non-internal diseases. Methods: Data from standardised blood pressure measurements conducted during the Czech European Health Examination Survey 2014 and information on health status and health care use collected during the Czech European Health Interview Survey 2014 were analyzed. We focused on participants aged 25–64. Data were weighted on sex and age to ensure an appropriate sex and age structure of the population. The χ2-test and binary logistic regression analyses were used to compare distribution of cascade of care for hypertension between the health-status groups of respondents. Results: The final eligible sample consisted of 1121 participants. The prevalence of hypertension was 32.8% in the healthy group, 29.8% in the non-internal disease group and 52.4% in the internal disease group, (p < 0.001). Awareness was 54.1%, 59.1% and 85.2% respectively, (p < 0.001). Treatment was 44.2%, 52.6% and 86.4%, respectively, (p < 0.001). Among apparently healthy respondents 62.6% had their blood pressure measured by a medical professional in the last year, compared to 71.1% in the non-internal disease group and 91.7% in the internal disease group, (p < 0.001). Differences in hypertension control were not statistically significant. Conclusions: Generally, our data show a discordance in hypertension management within the Czech population. Apparently healthy individuals are the least aware of their diagnosis and the highest proportion of them remain untreated. [ABSTRACT FROM AUTHOR]

Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility to infections and autoreactive T cells and resulting from defective genomic rearrangement of genes for the T cell and B cell receptors. The most frequent etiologies are hypomorphic mutations in "non-core" regions of the Rag1 or Rag2 genes, the protein products of which are critical members of the cellular apparatus for V(D)J recombination. In this report, we describe an infant with Omenn syndrome with a previously unreported termination mutation (p.R142*) in Rag1 on one allele and a partially characterized substitution mutation (p.V779M) in a "core" region of the other Rag1 allele. Using a cellular recombination assay, we found that while the p.R142* mutation completely abolished V(D)J recombination activity, the p.V779M mutation conferred a severe, but not total, loss of V(D)J recombination activity. The recombination defect of the V779 mutant was not due to overall misfolding of Rag1, however, as this mutant supported wild-type levels of V(D)J cleavage. These findings provide insight into the role of this poorly understood region of Rag1 and support the role of Rag1 in a post-cleavage stage of recombination.

Bioactive lipids, including oxylipins, endocannabinoids, and related compounds may function as specific biochemical markers of certain aspects of inflammation. However, the postprandial responsiveness of these compounds is largely unknown; therefore, changes in the circulating oxylipin and endocannabinoid metabolome in response to a challenge meal were investigated at six occasions in a subject who freely modified her usual diet. The dietary change, and especially the challenge meal itself, represented a modification of precursor fatty acid status, with expectedly subtle effects on bioactive lipid levels. To detect even the slightest alteration, highly sensitive ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS/MS) methods for bioactive lipid profiling was employed. A previously validated UPLC-ESI-MS/MS method for profiling the endocannabinoid metabolome was used, while validation of an UPLC-ESI-MS/MS method for oxylipin analysis was performed with acceptable outcomes for a majority of the parameters according to the US Food and Drug Administration guidelines for linearity (0.9938 < R2 < 0.9996), limit of detection (0.0005-2.1 pg on column), limit of quantification (0.0005-4.2 pg on column), inter- and intraday accuracy (85-115%) and precision (< 5%), recovery (40-109%) and stability (40-105%). Forty-seven of fifty-two bioactive lipids were detected in plasma samples at fasting and in the postprandial state (0.5, 1, and 3 hours after the meal). Multivariate analysis showed a significant shift of bioactive lipid profiles in the postprandial state due to inclusion of dairy products in the diet, which was in line with univariate analysis revealing seven compounds (NAGly, 9-HODE, 13-oxo-ODE, 9(10)-EpOME, 12(13)-EpOME, 20-HETE, and 11,12-DHET) that were significantly different between background diets in the postprandial state (but not at fasting). The only change in baseline levels at fasting was displayed by TXB2. Furthermore, postprandial responsiveness was detected for seven compounds (POEA, SEA, 9(10)-DiHOME, 12(13)-DiHOME, 13-oxo-ODE, 9-HODE, and 13-HODE). Hence, the data confirm that the UPLC-ESI-MS/MS method performance was sufficient to detect i) a shift, in the current case most notably in the postprandial bioactive lipid metabolome, caused by changes in diet and ii) responsiveness to a challenge meal for a subset of the oxylipin and endocannabinoid metabolome. To summarize, we have shown proof-of-concept of our UPLC-ESI-MS/MS bioactive lipid protocols for the purpose of monitoring subtle shifts, and thereby useful to address lipid-mediated postprandial inflammation.

Here we present the results of a large-scale bioinformatics annotation of non-coding RNA loci in 48 avian genomes. Our approach uses probabilistic models of hand-curated families from the Rfam database to infer conserved RNA families within each avian genome. We supplement these annotations with predictions from the tRNA annotation tool, tRNAscan-SE and microRNAs from miRBase. We identify 34 lncRNA-associated loci that are conserved between birds and mammals and validate 12 of these in chicken. We report several intriguing cases where a reported mammalian lncRNA, but not its function, is conserved. We also demonstrate extensive conservation of classical ncRNAs (e.g., tRNAs) and more recently discovered ncRNAs (e.g., snoRNAs and miRNAs) in birds. Furthermore, we describe numerous "losses" of several RNA families, and attribute these to either genuine loss, divergence or missing data. In particular, we show that many of these losses are due to the challenges associated with assembling avian microchromosomes. These combined results illustrate the utility of applying homology-based methods for annotating novel vertebrate genomes.

Transpiration efficiency (TE), the biomass produced per unit of water transpired, is a key trait for crop performance under limited water. As water becomes scarce, increasing TE would contribute to increase crop drought tolerance. This study is a first step to explore pearl millet genotypic variability for TE on a large and representative diversity panel. We analyzed TE on 537 pearl millet genotypes, including inbred lines, test-cross hybrids, and hybrids bred for different agroecological zones. Three lysimeter trials were conducted in 2012, 2013 and 2015, to assess TE both under well-watered and terminal-water stress conditions. We recorded grain yield to assess its relationship with TE. Up to two-fold variation for TE was observed over the accessions used. Mean TE varied between inbred and testcross hybrids, across years and was slightly higher under water stress. TE also differed among hybrids developed for three agroecological zones, being higher in hybrids bred for the wetter zone, underlining the importance of selecting germplasm according to the target area. Environmental conditions triggered large Genotype x Environment (GxE) interactions, although TE showed some high heritability. Transpiration efficiency was the second contributor to grain yield after harvest index, highlighting the importance of integrating it into pearl millet breeding programs. Future research on TE in pearl millet should focus (i) on investigating the causes of its plasticity i.e. the GxE interaction (ii) on studying its genetic basis and its association with other important physiological traits. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic presented a challenge for caregiving relatives in the home care setting. Caregivers can transmit SARS-CoV-2 to their relatives who are often at high risk for a severe course of COVID-19. Regular testing of asymptomatic caregivers for SARS-CoV-2 may reduce the risk of transmission. The optimal method and frequency of regular asymptomatic testing is unknown. We conducted a prospective, randomised trial to assess the feasibility, recruitment and acceptance of different testing frequencies. This serves to inform a future definitive randomised controlled trial. Methods: We carried out a parallel three-armed feasibility trial, enrolling adult participants who provided home-based care for a relative at least twice a week. Participants were randomly assigned using sealed envelopes to either conduct saliva-based antigen self-testing at a frequency of once a week (group I), twice a week (group II), or every two days (group III). The participants completed questionnaires on a weekly basis. Main outcome measures were feasibility of recruitment, adherence to self-tests and distress caused by self-testing. We further collected data on the use of mouth-nose mask. Results: From 25 March to 7 May 2021 we assessed 27 participants and randomised 26 in the study: 8 participants in group I, 8 in group II and 10 in group III. All participants completed the study. In group I 48/48 (100.0%; 95% CI 92.6% to 100.0%), in group II 93/96 (96.9%; 95% CI 91.2% to 98.9%) and in group III 209/210 (99.5%; 95% CI 97.4% to 99.9%) self-tests were carried out at home. Participants did not perceive regular self-testing as burdensome in any of the study arms. We did not observe any infection with SARS-CoV-2. During the study, mask adherence decreased from 35% to 19% in all groups. Conclusion: Conducting such a study was feasible. The participants tolerated regular self-testing well, which was reflected in a high level of test adherence. However, regular self-testing may have led to decreased protective behaviour. To demonstrate that regular asymptomatic testing reduces infection transmission, a future definitive trial should be performed at a time of a high prevalence of SARS-CoV-2 and be implemented as a multicentre study. Trial registration: The trial is registered with the German Clinical Trials Register, DRKS00026234. [ABSTRACT FROM AUTHOR]

In Europe, two fastidious phloem-limited pathogens, 'Candidatus Phytoplasma solani' (16SrXII-A) and 'Candidatus Arsenophonus phytopathogenicus', are associated with rubbery taproot disease (RTD) and syndrome basses richesses (SBR) of sugar beet, respectively. Both diseases can significantly reduce yield, especially when accompanied by root rot fungi. This study investigates the presence, geographic distribution and genetic traits of fastidious pathogens and the accompanying fungus, Macrophomina phaseolina, found on sugar beet across four geographically separated plains spanning seven countries in Central Europe. The survey revealed variable incidences of symptoms linked to these fastidious pathogens in the Pannonian and Wallachian Plains, sporadic occurrence in the North European Plain, and no symptomatic sugar beet in the Bohemian Plain. Molecular analyses unveiled the occurrence of both 'Ca. P. solani' and 'Ca. A. phytopathogenicus' throughout Central Europe, with a predominance of the phytoplasma. These fastidious pathogens were detected in all six countries surveyed within the Pannonian and Wallachian Plains, with only a limited presence of various phytoplasmas was found in the North European Plain, while no fastidious pathogens were detected in Bohemia, aligning with observed symptoms. While 16S rDNA sequences of 'Ca. P. solani' remained highly conserved, multi-locus characterization of two more variable loci (tuf and stamp) unveiled distinct variability patterns across the plains. Notably, the surprising lack of variability of tuf and stamp loci within Central Europe, particularly the Pannonian Plain, contrasted their high variability in Eastern and Western Europe, corresponding to epidemic and sporadic occurrence, respectively. The current study provides valuable insights into the genetic dynamics of 'Ca. P. solani' in Central Europe, and novel findings of the presence of 'Ca. A. phytopathogenicus' in five countries (Slovakia, Czech Republic, Austria, Serbia, and Romania) and M. phaseolina in sugar beet in Slovakia. These findings emphasize the need for further investigation of vector–pathogen(s)–plant host interactions and ecological drivers of disease outbreaks. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between corneal diameter and internal corneal span determined from angle-to-angle distance using ultrasound biomicroscopy (UBM) in an observational cross-sectional patient population comprised of 54 eyes (28 healthy control eyes, ages 0.1 to 11.3 years; 26 eyes with primary congenital glaucoma, ages 0.1 to 3.5 years) from 41 pediatric participants ages 0.1 to 11.3 years (mean age: 3±3 years, median age: 2 years). Methods: Forty cornea photographs with reference ruler and 110 UBM images were obtained. Three observers measured horizontal and vertical corneal diameter and angle-to-angle distance in each cornea photo and UBM image using ImageJ and the average values were used. Main outcome measures were Pearson correlation coefficient, linear regression, mean difference between corneal diameter and angle-to-angle distance, and intra-class correlation coefficients among measurements from all three observers for each parameter. Results: Corneal diameter and angle-to-angle distance had a strong positive correlation horizontally (Pearson r = 0.89, p<0.001) and vertically (r = 0.93, p<0.001). Correlation was consistent regardless of presence of primary congenital glaucoma and participant age. Regression analysis demonstrated a linear relationship between the parameters for horizontal (CD = 0.99*AA+0.28, R2 = 0.81, p<0.001) and vertical (CD = 0.91 *AA+1.32, R2 = 0.85, p<0.001) dimensions. Overall, reliability was good-excellent, ranging from an ICC of 0.76 for vertical corneal diameter to 0.90 for horizontal angle-to-angle distance. Conclusions: Based on the strong positive correlation found between corneal diameter and angle-to-angle distance in our study population, UBM image analysis can be used to accurately estimate corneal diameter from angle-to-angle distance in children with healthy eyes and primary congenital glaucoma. UBM may provide a useful intraocular alternative for estimating corneal diameter and monitoring diseases that affect the cornea in infants and children, such as congenital glaucoma. [ABSTRACT FROM AUTHOR]