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We reanalyse the recent compilation of distance measurements to M87 by collecting the data from published literature. Different from the traditional statistical methods, based on the principle of minimum information loss, we use a robust most frequent value (MFV) procedure to estimate the distance to M87, irrespective of the Gaussian or non-Gaussian distributions. The MFV-based robust estimate for the M87 distance modulus is given by |$31.09^{+0.04}_{-0.03}$| (statistical) |$^{+0.05}_{-0.07}$| (systematic) mag corresponding to a 68.27 per cent confidence interval, whereas the result of combining the two uncertainties in quadrature is |$31.09^{+0.06}_{-0.08}$|  mag. We also construct the error distributions of M87 distance moduli values according to the weighted mean, median, and MFV, which is non-Gaussian. This demonstrates that the MFV method offers a more accurate and robust estimate of the distance to M87 compared to methods that depend on the unfulfilled assumption of Gaussianity. [ABSTRACT FROM AUTHOR]

We introduce the parity-odd power (POP) spectra, a novel set of observables for probing parity violation in cosmological N -point statistics. POP spectra are derived from composite fields obtained by applying non-linear transformations, involving also gradients, curls, and filtering functions, to a scalar field. This compresses the parity-odd trispectrum into a power spectrum. These new statistics offer several advantages: they are computationally fast to construct, estimating their covariance is less demanding compared to estimating that of the full parity-odd trispectrum, and they are simple to model theoretically. We measure the POP spectra on simulations of a scalar field with a specific parity-odd trispectrum shape. We compare these measurements to semi-analytic theoretical calculations and find agreement. We also explore extensions and generalizations of these parity-odd observables. [ABSTRACT FROM AUTHOR]

Background Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. Methods In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. Results The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P >.05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P =.036, odds ratio = 2.09 [95% CI = 1.31-5.95]). Conclusions We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies. [ABSTRACT FROM AUTHOR]

Objective This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA. Methods A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels. Results In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (β = 0.795, CI 95%, 0.196-1.395; P =.010), -SH/(-SH+-SS) (β = -0.475, CI 95%, 0.114-0.836; P =.010) and IMA (β = 3.932, CI 95%, 0.859-7.005; P =.013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI. Conclusion In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices. [ABSTRACT FROM AUTHOR]

Background Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC. Methods We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model. Results We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P =.022). The results of both studies were robust and neither had publication bias. Conclusion Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size. [ABSTRACT FROM AUTHOR]

Objectives Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. Methods Serum samples from patients within the MyoCite cohort, a well-characterized retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017–2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patients' serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against immunoprecipitation as the reference standard, measuring sensitivity, specificity and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific myositis-specific autoantibodies. Results Immunoprecipitation identified myositis autoantibodies in 56.5% (n  = 83) of patient samples, with anti-Jo1 (n  = 16; 10.9%) as the most common, followed by anti-MDA5 (n  = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83 and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and immunoprecipitation, and κ values for LIAs for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2 and anti-SAE ranged between 0.21 and 0.60. Conclusion While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5 and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor. [ABSTRACT FROM AUTHOR]

While researchers commonly use the bootstrap to quantify the uncertainty of an estimator, it has been noticed that the standard bootstrap, in general, does not work for Chatterjee's rank correlation. In this paper, we provide proof of this issue under an additional independence assumption, and complement our theory with simulation evidence for general settings. Chatterjee's rank correlation thus falls into a category of statistics that are asymptotically normal, but bootstrap inconsistent. Valid inferential methods in this case are Chatterjee's original proposal for testing independence and the analytic asymptotic variance estimator of Lin & Han (2022) for more general purposes. [ Received on 5 April 2023. Editorial decision on 10 January 2024] [ABSTRACT FROM AUTHOR]

Estimation of the time-average variance constant is important for statistical analyses involving dependent data. This problem is difficult as it relies on a bandwidth parameter. Specifically, the optimal choices of the bandwidths of all existing estimators depend on the estimand itself and another unknown parameter that is very difficult to estimate. Thus, optimal variance estimation is unachievable. In this paper, we introduce a concept of converging flat-top kernels for constructing variance estimators whose optimal bandwidths are free of unknown parameters asymptotically and hence can be computed easily. We prove that the new estimator has an asymptotically constant risk and is locally asymptotically minimax. [ABSTRACT FROM AUTHOR]

Subgraph counts, in particular the number of occurrences of small shapes such as triangles, characterize properties of random networks. As a result, they have seen wide use as network summary statistics. Subgraphs are typically counted globally, making existing approaches unable to describe vertex-specific characteristics. In contrast, rooted subgraphs focus on vertex neighbourhoods, and are fundamental descriptors of local network properties. We derive the asymptotic joint distribution of rooted subgraph counts in inhomogeneous random graphs, a model that generalizes most statistical network models. This result enables a shift in the statistical analysis of graphs, from estimating network summaries to estimating models linking local network structure and vertex-specific covariates. As an example, we consider a school friendship network and show that gender and race are significant predictors of local friendship patterns. [ABSTRACT FROM AUTHOR]

The postdisaster experiences of 167 social work students in the aftermath of the Great Flood of 2016 were examined. Using a cross-sectional survey design and validated self-report measures, the current study examined the association between students' protective factors (hope, altruism, spiritual support; at 8, 20, and 12 items, respectively) and six adaptive coping mechanisms, and further sought to determine whether such associations varied according to students' race (white vs. African American). Six hierarchical multiple linear regression analyses were conducted using each of the adaptive coping strategies (acceptance, active coping, positive reframing, self-distraction, planning, and venting). Results showed that students' race moderated the associations between altruism and active coping, spiritual support and active coping, spiritual support and self-distraction, altruism and planning, spiritual support and planning, and altruism and venting. The decomposition of the significant interactions indicated that the effect of altruism on active coping, planning, and venting was greater among white than among African American participants; the effect of spiritual support on active coping, self-distraction, and planning was greater among African American than among white participants. Recommendations include educating all students about risks incurred when working with traumatized populations. Research examining postdisaster coping responses of social workers can inform culturally responsive supervision approaches. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. Study Design In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. Study Results Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P  < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P  < .05, false discovery rate correction). Conclusions Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients. [ABSTRACT FROM AUTHOR]

Background Following the Taliban's resurgence, Afghan girls were probited from attending school and university, likely causing adverse psychological effects. Therefore, the present study investigated depression, suicidal ideation, and quality of life (QoL) among Afghan girls banned from education by the Taliban. Methods A survey study assessed depression, suicidal ideation, and QoL among 426 females prohibited from attending secondary schools, high schools, and universities by the Taliban. The study used the CES-D 20 Scale to assess depression, and the WHOQOL-Bref Questionnaire to assess QoL. Associations between variables were tested with chi-square tests, and predictors of QoL were analyzed through multivariate regression analysis. Results Among the 426 participants, 87.6% exhibited depression symptoms and 49.8% reported suicidal thoughts. Significant predictors of overall QoL included monthly family income (B  = 0.147, P  = 0.001), recent others' behavior toward participants (B  = −0.247, P  < 0.001), physical illness (B  = 0.110, P  = 0.011), experiencing a recent traumatic event (B  = 0.108, P  = 0.015), depression (B  = −0.159, P  < 0.001) and suicidal ideation (B  = −0.187, P  < 0.001). Conclusions In Taliban-ruled Afghanistan, the results indicated that female students who have been prohibited from studying in classes have a high prevalence of depression and suicidal ideation. Having depression and suicidal ideation significantly predicted decreased quality of life among female students. [ABSTRACT FROM AUTHOR]

Background Many individuals with chronic obstructive pulmonary disease (COPD) experience frequent hospitalization and readmissions, which is burdensome on the health system. This study aims to investigate factors associated with unplanned readmissions and mortality following a COPD-related hospitalization over a 12-month period in Australia, focusing on mental disorders and accounting for the acute phase of the COVID-19 pandemic. Methods A retrospective cohort study using linked hospitalization and mortality records identified individuals aged ≥40 years who had at least one hospital admission with a principal diagnosis of COPD between 2014 and 2020 in New South Wales, Australia. A semi-competing risk analysis was conducted to examine factors associated with unplanned readmission and mortality. Results Adults with a mental disorder diagnosis, specifically anxiety, had a higher risk of 12-month unplanned readmission. Individuals with anxiety and dementia also had a higher risk of mortality pre- and post-unplanned readmission. Individuals who were admitted during the acute phase of the COVID-19 pandemic period had lower risk of unplanned readmission, but higher risk of mortality without unplanned readmission. Conclusion Interventions aimed at reducing admissions should consider adults living with mental disorders such as anxiety or dementia to improve healthcare delivery and health outcomes for individuals living with COPD. [ABSTRACT FROM AUTHOR]

Background As per the National Family Health Survey (NFHS-4, 2015–16) report, 40% of women aged 15–49 in India experienced intimate partner violence (IPV), with emotional abuse significantly associated with negative reproductive health (RH) outcomes. Methods The study uses secondary data from the NFHS-4 and conducts statistical analysis based on information gathered from 8766 married women aged 15–49 years in Northeast India. Bivariate analysis followed by multiple logistic regression analysis is performed to understand the relationship between IPV and its effects on women's RH. Results The findings indicate that ever-married women in Northeast India have faced physical violence (25.1%), sexual violence (11.8%), emotional abuse (6.4%) and severe violence (5.3%). Among all women who participated in the study, 6.9% had experienced non-live births, 4.2% miscarriages, 2.4% abortions, 0.3% stillbirths, 16.9% terminated pregnancies and 2.1% sexually transmitted infections (STI). Sexually abused women (SAW) showed higher likelihoods of non-live births, STIs, miscarriages, abortions and pregnancy terminations. SAW had a 65% higher risk of miscarriages, while those experiencing physical violence had a 64% increased risk of abortions. Conclusion IPV significantly impacts women's RH in Northeast India. This study presents evidence from surveys on sexual and RH among married women affected by IPV in Northeast India. [ABSTRACT FROM AUTHOR]

Background The health and environmental benefits of legume consumption are reflected in dietary guidelines worldwide. However, legume intake fails to meet recommendations. Dietitians' legume counseling practices can impact consumption patterns. This cross-sectional study assessed Israeli dietitians' knowledge, attitudes, perceptions and practices regarding legume counseling and identified pertinent barriers and facilitators. Methods An electronic survey among Israeli dietitians (n  = 309) was performed. Multivariable logistic regression assessed associations between recommending legumes with participants' socio-demographic and professional characteristics, knowledge, perceptions, attitudes toward legume counseling and personal legume intake. Results Almost half (47.4%) of the participants recommended that 76% or more of their patients increase legume intake. Factors that were associated with recommending legumes were perceptions of fewer barriers to consumption [adjusted OR (aOR) 1.92 (95% CI 1.24–2.96)] and positive attitudes toward legume counseling pertaining to its importance [aOR 1.95 (95% CI 1.12–3.4)]. Negatively associated factors were a low level of personal legume consumption [aOR 0.38 (95% CI 0.15–0.94)] and working in hospitals [aOR 0.43 (95% CI 0.19–0.98)]. Conclusions Israeli dietitians' recommendations for legume consumption were well below current guidelines. These findings indicate the need for a tailored intervention for nutrition professionals to increase the frequency of legume counseling and overall consumption. [ABSTRACT FROM AUTHOR]

Background Malnutrition is a public health problem that affects physical and psychosocial well-being. It manifests as a rapid deterioration in nutritional status and bilateral edema due to inadequate food intake or illness. Methods This study is a retrospective cohort of 1208 children with severe acute malnutrition (SAM) in Sofala Province from 2018 to 2022. It includes hospitalized children aged 6–59 months with SAM and related complications. The dependent variable is recovery, and the independent variables include age, sex of the child, vomiting, dehydration, hypoglycemia, nutritional edema and anthropometry. Survival curves were plotted using the Kaplan–Meier method, and bivariable and multivariable Cox regression analyses were performed. Results The crude analysis revealed significant factors for nutritional recovery in children with SAM, including age, weight, height, malaria, diarrhea and dehydration. Children under 24 months had a 28% lower likelihood of recovery. Weight below 6.16 kg decreased the likelihood by 2%, and height above 71.1 cm decreased it by 20%. Conversely, malaria, diarrhea and dehydration increased the likelihood of recovery. However, after adjustment, only diarrhea remained a significant predictor of nutritional recovery. Conclusion This study found that diarrhea is a predictor of nutritional recovery in children with SAM. [ABSTRACT FROM AUTHOR]

Aims Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood. Methods and results We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram–CMR agreement. Bland–Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P < 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI −0.0002, +0.0005 mm/m/year). Conclusion MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS. [ABSTRACT FROM AUTHOR]

Purpose The influence of Open Access (OA) on the citation impact of scholarly articles remains a topic of considerable debate. This study aims to elucidate the relationship between OA publication and citation metrics, as well as article visibility, within the context of the Postgraduate Medical Journal (PMJ). Methods We conducted a retrospective analysis of 373 articles published in PMJ between 2020 and 2021. Data on OA status, citations, page views, PDF downloads, and other relevant variables were extracted from Journal Citation Reports and PMJ's official website. Multivariable linear regression and other statistical analyses were used to assess the impact of OA on these metrics. Results OA articles (n  = 78) demonstrated significantly higher citation counts, page views, and PDF downloads compared with subscription-based articles (n  = 295). Specifically, OA articles showed a significant increase in citation frequency with a β coefficient of 25.08 and a 95% CI of 17.168–32.992 (P  < .001). Similarly, OA status was independently associated with increases in page views [β = 288.636, 95%CI: 177.749–399.524, P  < .001] and PDF downloads [β = 118.966, 95%CI: 86.357–151.575, P  < .001]. Strong correlations among total citations, page views, and PDF downloads were observed in both OA and subscription articles. Conclusion The study highlights a significant and independent association of OA publishing with increased citation counts, page views, and PDF downloads in PMJ, suggesting that OA articles have broader reach and greater visibility. Further research, including randomized controlled studies across various journals, is needed to confirm these findings and explore the full impact of OA publishing. Key message 1. What is already known on this topic: Prior research on the impact of Open Access (OA) on scholarly articles has produced mixed results, with some studies indicating a citation advantage for OA articles in various fields, while others found no significant difference. This inconsistency in findings across disciplines highlighted the need for a focused study on the citation impact of OA in specific journals such as the Postgraduate Medical Journal (PMJ). 2. What this study adds: Our study uniquely demonstrates that OA articles in PMJ are associated with significantly higher citation counts, page views, and PDF downloads compared with subscription-based articles. It highlights a notable correlation between OA article visibility (as measured by page views and downloads) and citation counts, thereby enriching the current understanding of the benefits of OA publishing. 3. How this study might affect research, practice, or policy: These findings suggest a considerable advantage of OA publishing in increasing the visibility and impact of research. They highlight the potential benefits for journals and policymakers in advocating OA publications and underscore the strategic advantage for researchers in opting for OA to achieve wider dissemination and impact. This study may also serve as a catalyst for further research into the varied effects of OA across different disciplines and journal types. [ABSTRACT FROM AUTHOR]

This paper presents analytical results on the anatomy of nested sampling, from which a technique is developed to estimate the run-time of the algorithm that works for any nested sampling implementation. We test these methods on both toy models and true cosmological nested sampling runs. The method gives an order-of-magnitude prediction of the endpoint at all times, forecasting the true endpoint within standard error around the halfway point. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI],.7–1.5; P =.98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI,.7–1.7; P =.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT 04315948; EudraCT 2020-000936-23. [ABSTRACT FROM AUTHOR]

Background The management of multidrug-resistant tuberculosis (MDR-TB) remains challenging. Treatment outcome is influenced by multiple factors; the specific roles of diabetes and glycemic control remain uncertain. This study aims to assess the impact of glycemic control on drug exposure, to investigate the association between drug exposure and treatment outcomes, and to identify clinically significant thresholds predictive of treatment outcome, among patients with diabetes. Methods This multicenter prospective cohort study involved patients with confirmed MDR-TB and diabetes. Drug exposure level was estimated by noncompartmental analysis. The minimum inhibitory concentrations (MICs) were determined for the individual Mycobacterium tuberculosis isolates. The influence of poor glycemic control (glycated hemoglobin ≥7%) on drug exposure and the associations between drug exposure and treatment outcome were evaluated by univariate and multivariate analysis. Classification and regression tree analysis was used to identify the drug exposure/susceptibility thresholds. Results Among the 131 diabetic participants, 43 (32.8%) exhibited poor glycemic control. Poor glycemic control was independently associated with decreased exposure to moxifloxacin, linezolid, bedaquiline, and cycloserine, but not clofazimine. Additionally, a higher ratio of drug exposure to susceptibility was found to be associated with a favorable MDR-TB treatment outcome. Thresholds predictive of 6-month culture conversion and favorable outcome were bedaquiline area under the concentration–time curve (AUC)/MIC ≥245 and moxifloxacin AUC/MIC ≥67, demonstrating predictive accuracy in patients, regardless of their glycemic control status. Conclusions Glycemic control and optimal TB drug exposure are associated with improved treatment outcomes. This dual management strategy should be further validated in randomized controlled trials of patients with MDR-TB and diabetes. [ABSTRACT FROM AUTHOR]

Background Tuberculosis is a leading cause of death worldwide, and food insecurity is known to negatively influence health outcomes through multiple pathways. Few studies have interrogated the relationship between food insecurity and tuberculosis outcomes, particularly independent of nutrition. Methods We conducted a prospective cohort study of adults initiating first-line treatment for clinically suspected or microbiologically confirmed drug-sensitive tuberculosis at a rural referral center in Haiti. We administered a baseline questionnaire, collected clinical data, and analyzed laboratory samples. We used logistic regression models to estimate the relationship between household food insecurity (Household Hunger Scale) and treatment failure or death. We accounted for exclusion of patients lost to follow-up using inverse probability of censoring weighting and adjusted for measured confounders and nutritional status using inverse probability of treatment weighting. Results We enrolled 257 participants (37% female) between May 2020 and March 2023 with a median age (interquartile range) of 35 (25–45) years. Of these, 105 (41%) had no hunger in the household, 104 (40%) had moderate hunger in the household, and 48 (19%) had severe hunger in the household. Eleven participants (4%) died, and 6 (3%) had treatment failure. After adjustment, food insecurity was significantly associated with subsequent treatment failure or death (odds ratio 5.78 [95% confidence interval, 1.20–27.8]; P =.03). Conclusions Household food insecurity at tuberculosis treatment initiation was significantly associated with death or treatment failure after accounting for loss to follow-up, measured confounders, and nutritional status. In addition to the known importance of undernutrition, our findings indicate that food insecurity independently affects tuberculosis treatment outcomes in Haiti. [ABSTRACT FROM AUTHOR]

Aims To compare patient-reported outcomes (PROs) in patients newly (<6 months) diagnosed with atrial fibrillation (AF) with those who have had a longer diagnosis (≥6 months) and to investigate whether or not these outcomes change over a 6-month period. Methods and results In this longitudinal survey study, 129 patients with AF completed the Revised Illness Perception Questionnaire, the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia, and the Hospital Anxiety and Depression Scale at baseline and after 6 months. At baseline, patients newly diagnosed with AF (n = 53), compared with patients with a previous diagnosis (n = 76), reported AF as more temporary (P = 0.003) and had a higher belief in personal and treatment control (P = 0.004 and P = 0.041, respectively). At a 6-month follow-up, patients newly diagnosed reported a lower symptom burden (P = 0.004), better health-related quality of life (HRQoL); (P = 0.015), and a higher personal control (P < 0.001) than patients previously diagnosed. Over time, in patients newly diagnosed, symptom burden and the anxiety symptom score decreased (P = 0.001 and P = 0.014, respectively) and HRQoL improved (P = 0.002). Conclusion Patients newly diagnosed with AF reported more positive PROs both at baseline and at a 6-month follow-up than patients with a previous diagnosis of AF. Therefore, it is important to quickly capture patients newly diagnosed to support their belief in their own abilities. Such support may, alongside medical treatments, help patients manage the disease, which may lead to reduced symptom burden and better HRQoL over time. [ABSTRACT FROM AUTHOR]

Objective Total knee replacement (TKR) is a common solution for patients with advanced knee osteoarthritis (OA). Still, fall rates remain relatively high after surgery. TKR may alter pain and knee function, balance control, and proprioception. However, given the role of complex (dual-task) walking in fall prediction for older adults, it is unknown how TKR alters the attentional demand of walking in older adults. The goal of this study was to examine the effect of TKR on dual-task walking among older adults. Methods Participants were evaluated 1 month before surgery and 4.5 months after surgery. Participants walked along an instrumented 7-meter path for 1 minute with and without a cognitive task (serial-3 subtraction). Pain and knee function, knee proprioception, dynamic balance, and balance confidence, as well as dual-task costs (DTC) were compared before and after the surgery and factors associated with change in gait DTCs were assessed. Results Thirty-eight participants completed the study (age 72.6 years, SD = 4.9; 11 men). A significant decrease in pain was found following TKR, with no change in balance, balance confidence, or proprioception. There were no differences in gait DTCs before and after the surgery. However, change in dynamic balance, specifically reactive postural control and dynamic gait, predicted changes in gait speed and stride time DTCs. Conclusion The absence of an effect of TKR on gait DTCs can potentially underlie increased fall risk after TKR. Results from this study emphasize the significance of balance as a measure and focal point for rehabilitation after TKR. Impact This study contributes to our understanding of the attentional cost of walking in people before and after TKR, as well as to factors associated with it. Results from this work can assist formulation of rehabilitation programs for people with knee OA. [ABSTRACT FROM AUTHOR]

The European Health Literacy Survey Questionnaire (HLS-EU-Q47) is available in multiple languages, and shortened versions have also been developed. This study aimed to examine the reliability and validity of the short version of the questionnaire (HLS-Q12) developed for community-dwelling older adults in Japan. The HLS-Q12 was developed using 12 of the 47 items of the Japanese version of the HLS-EU-Q47. In this study, the survey was conducted by distributing self-administered questionnaires to community-dwelling individuals aged 65 years and older who consented to participate; their responses were collected by mail. The correlation between the HLS-Q12 and the HLS-EU-Q47 was tested to assess criterion validity. To test construct validity, nine novel hypotheses were proposed. We also conducted a confirmatory factor analysis of the HLS-Q12. Based on a resurvey after 5–7 days, test–retest reliability was examined using interclass correlation coefficients (ICCs) and Bland–Altman analysis. In total, 118 individuals provided valid responses to the questionnaire. The Spearman rank correlation coefficient between the HLS-Q12 and the HLS-EU-Q47 was r  = 0.98 (p  < 0.001), and eight of the nine hypotheses were supported. The ICC was 0.96 (p  < 0.001), and the 95% limit of agreement was −0.26 ± 5.9, suggesting no systematic error. Thus, the Japanese version of the HLS-Q12 was found to be reliable with high criterion validity and reproducibility. Hence, the HLS-Q12 is a useful scale for measuring health literacy among older adults in Japan. [ABSTRACT FROM AUTHOR]

This study sought to analyze an explanatory model on the relationship among sociodemographic factors, health-promoting lifestyle behaviors and psychological distress (depression, anxiety and stress) in college students. This is an observational, analytical and cross-sectional study conducted on a national sample of 4203 students who entered a macro university in Honduras in 2021, 2022 and 2023. We used a sociodemographic survey, the Health-Promoting Lifestyle Profile (HPLP-II) and the Depression, Anxiety and Stress Scales (DASS-21). Univariate analysis and a multivariate structural equation model were conducted. The average HPLP-II score was 117.45 (± 23.41), and the average DASS-21 score was 20.06 (± 14.16). The multivariate model showed a good data fit (comparative fit index = 0.951; Tucker–Lewis index = 0.957; root mean square error of approximation = 0.067 [90% CI = 0.067–0.068]). Results indicate that being a woman (β = 0.11; p  < 0.001) and being enrolled in biological and health sciences (β = 0.09; p  < 0.001) significantly predict HPLP-II scores. Furthermore, being a woman (β = 0.17; p  < 0.001), age (β = 0.10; p  < 0.001) and having pre-existing medical conditions (β = 0.16; p  < 0.001) significantly explain part of the variance of DASS-21. A significant reverse relationship between health-promoting behavior and psychological distress was shown (r  = −0.36; p  < 0.001). This study identifies protective and risky sociodemographic factors linked to health-promoting lifestyle behaviors and psychological distress. Our findings have implications for developing comprehensive intervention policies and strategies to promote health in higher education settings. [ABSTRACT FROM AUTHOR]

Considering that a sizable segment of the population spends significant amount of time at work, workplaces have been identified as practical platforms for health educational programs. Although employee wellness programs in high-income countries have shown measurable benefits in productivity and physical and mental health, evidence-based programs in low- and middle-income countries, such as Lebanon, are unavailable. The aim is to develop and implement a pilot workplace wellness program focusing on health-related areas to improve health knowledge and behavior among working men and women of reproductive age. In collaboration with March of Dimes, the National Collaborative Perinatal Neonatal Network developed a culturally sensitive health education program focusing on lifestyle, infection, nutrition and family planning. Sessions were delivered by a multidisciplinary team of specialists at a local bank in Lebanon. To assess the impact of the program, participants completed Knowledge and Behavior Assessment Questionnaire (KBAQ) before and after implementation. KBAQ was conducted 6 months after implementation to measure retention and continuing impact. Forty-seven participants completed the program, of whom 44.7% are male, 98% have university degree and 56.5% are married. Total knowledge score improved significantly from 64.2 to 74.3 and remained significant at 6 months post-implementation with a score of 71.7 (p  < 0.001). At 6-month follow-up, emotional score improved (p  = 0.028), while smoking decreased (p  = 0.008). Also, employees' health knowledge and behavior showed sustained and significant improvement. We plan to implement our program at other sites and among employees from different backgrounds to understand the impact of the wellness program on employees' knowledge and behaviors at a larger scale. [ABSTRACT FROM AUTHOR]

Teachers play a crucial role in students' learning and in the development of health literacy. Hence, the aim of this study was to identify the core competencies needed for teachers of health education in supporting student learning. A three-round Delphi study was carried out over an 8-week period, through consultation with 25 Finnish experts in health education. An open-ended question was used to identify the core competencies for school health educators. The data were analysed using inductive content analysis. In subsequent rounds, experts were asked to assess the importance of the identified competencies on a 7-point Likert scale, and finally to rank the most important competencies. In total, 52 competencies were identified and categorized into eight core competence domains. Thereafter, 40 competencies were assessed and selected for the third round, in which the experts ranked the 15 most important competencies, encompassing four core domains, i.e. pedagogic and subject-specific didactic, social and emotional, content knowledge and continuous professional development. Other domains of competence identified in the present study were ethical competence, competence in school health promotion, contextual competence and professional well-being competence. The study defines health education teacher core competencies and domains, and the information can be used in teacher education programmes, for developing teaching and for teachers' self-evaluation. [ABSTRACT FROM AUTHOR]

Limited health literacy is linked to unhealthy behaviors, adverse health outcomes, poor quality of life and financial burdens on society. However, little is known about the level of health literacy, especially among school-going children. This cross-sectional study assesses health literacy levels and their determinants in 354 school children from Kathmandu Metropolitan City, utilizing a multi-stage cluster sampling method. The 10-item Health Literacy for School-Aged Children was used to measure the student's literacy levels. Bivariate analysis and multivariable logistic regression at the significance level of 0.05 were performed to determine factors associated with limited health literacy. The majority of participants (76.6%) had moderate health literacy, while 13.8% had a high level and 9.6% had a low level of health literacy. Students from nuclear families had lower odds [adjusted odds ratio (aOR): 0.4; 95% CI: 0.2–0.8] of having limited health literacy. Students whose mother education was up to secondary school (aOR: 10.1; 95% CI: 1.3–78.9), students with pre-existing mental health conditions (aOR: 3.7; 95% CI: 1.4–9.6) and students with unsatisfactory health status (aOR: 3.9; 95% CI: 1.5–10.5) had higher odds to have limited health literacy. These results suggest the importance of prioritizing school health promotion and education activities for students with pre-existing mental health conditions and mothers with low educational attainment. Implementing peer support group programs for children with mental illnesses, mobilizing school health professionals and introducing interventions such as vocational training of mothers can collectively improve health literacy among school-going children. [ABSTRACT FROM AUTHOR]

Summary We introduce WatFinder , a tool designed to identify and visualize protein–water interactions (water bridges, water-mediated associations, or water channels, fluxes, and clusters) relevant to protein stability, dynamics, and function. WatFinder is integrated into ProDy , a Python API broadly used for structure-based prediction of protein dynamics. WatFinder provides a suite of functions for generating raw data as well as outputs from statistical analyses. The ProDy framework facilitates comprehensive automation and efficient analysis of the ensembles of structures resolved for a given protein or the time-evolved conformations from simulations in explicit water, as illustrated in five case studies presented in the Supplementary Material. Availability and implementation ProDy is open-source and freely available under MIT License from https://github.com/ProDy/ProDy. [ABSTRACT FROM AUTHOR]

Summary Hydrogen–Deuterium Exchange Mass Spectrometry (HDX-MS) is a powerful protein characterization technique that provides insights into protein dynamics and flexibility at the peptide level. However, analyzing HDX-MS data presents a significant challenge due to the wealth of information it generates. Each experiment produces data for hundreds of peptides, often measured in triplicate across multiple time points. Comparisons between different protein states create distinct datasets containing thousands of peptides that require matching, rigorous statistical evaluation, and visualization. Our open-source R package, HDXBoxeR, is a comprehensive tool designed to facilitate statistical analysis and comparison of multiple sets among samples and time points for different protein states, along with data visualization. Availability and implementation HDXBoxeR is accessible as the R package (https://cran.r-project.org/web//packages/HDXBoxeR) and GitHub: mkajano/HDXBoxeR. [ABSTRACT FROM AUTHOR]

The number of genome assemblies has rapidly increased in recent history, with NCBI databases reaching over 41,000 eukaryotic genome assemblies across about 2,300 species. Increases in read length and improvements in assembly algorithms have led to increased contiguity and larger genome assemblies. While this number of assemblies is impressive, only about a third of these assemblies have corresponding genome size estimations for their respective species on publicly available databases. In this paper, genome assemblies are assessed regarding their total size compared to their respective publicly available genome size estimations. These deviations in size are assessed related to genome size, kingdom, sequencing platform, and standard assembly metrics, such as N50 and BUSCO values. A large proportion of assemblies deviate from their estimated genome size by more than 10%, with increasing deviations in size with increased genome size, suggesting nonprotein coding and structural DNA may be to blame. Modest differences in performance of sequencing platforms are noted as well. While standard metrics of genome assessment are more likely to indicate an assembly approaching the estimated genome size, much of the variation in this deviation in size is not explained with these raw metrics. A new, proportional N50 metric is proposed, in which N50 values are made relative to the average chromosome size of each species. This new metric has a stronger relationship with complete genome assemblies and, due to its proportional nature, allows for a more direct comparison across assemblies for genomes with variation in sizes and architectures. [ABSTRACT FROM AUTHOR]

The main objective of mapping quantitative trait loci (QTL) and genome-wide association studies (GWAS) is to identify and locate QTLs on the genome. Estimating the sizes of QTL is equally important as identifying the QTLs. The size of a QTL is often measured by the QTL variance, or the proportion of phenotypic variance explained by the QTL, known as the QTL heritability. The reported QTL heritability is biased upward for small-sized QTLs estimated from small samples, especially in GWAS with a very small P -value threshold accommodating to Bonferroni correction for multiple tests. The phenomenon is called the Beavis effect. Methods of correcting the Beavis effect have been developed for additive effect models. Corresponding methods are not available for QTLs with more than one effect, such as QTLs including dominance and other genetic effects. In this study, we developed explicit formulas for estimating the variances and heritability for QTL with multiple effects. We also developed a method to remove nuisance parameters via an annihilator matrix. Finally, biases in estimated QTL variances caused by the Beavis effect are investigated and corrected. The new method is demonstrated by analyzing the 1000 grain weight (KGW) trait in a hybrid rice population. [ABSTRACT FROM AUTHOR]

Objective To develop the optimal US scanning protocol for the diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Methods In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls with a negative synovial fluid analysis were prospectively enrolled in two Italian Institutions. Four rheumatologists, blinded to patients' clinical details, performed US examinations using a standardized scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from second to fifth fingers, hips, knees, ankles). CPPD was identified as presence/absence, according to the OMERACT definitions. Reduced US scanning protocols were developed by selecting the most informative joints to be imaged by US using the LASSO technique. Patients were randomly divided into training and validation sets. Their diagnostic accuracy was tested comparing the area under the receiver operating characteristic curves. Results The number of participants enrolled was 204: 102 with CPPD disease and 102 disease controls [age, mean (s. d.): 71.3 (12.0) vs 71.1 (13.5) years; female: 62.8% vs 57.8%]. The median number of joints with US evidence of CPPD was 5 [interquartile range (IQR): 4–7] and 0 (IQR: 0–1) in patients with CPPD disease and controls, respectively (P  < 0.01). The detection of CPPD in ≥2 joints using a reduced scanning protocol (bilateral assessment of knees, wrists and hips) showed a sensitivity of 96.7% (95% CI: 82.8, 99.9) and a specificity of 100 (95% CI: 88.8, 100.0) for the diagnosis of CPPD disease and had good feasibility [mean (s. d.): 12.5 (5.3) min]. Conclusion Bilateral US assessment of knees, wrists and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease. [ABSTRACT FROM AUTHOR]

Objectives SLE is a systemic autoimmune disease characterized by heterogeneous manifestations and severity, with frequent lung involvement. Among pulmonary function tests, the measure of the diffusing capacity of the lungs for carbon monoxide (DLCO) is a noninvasive and sensitive tool assessing pulmonary microcirculation. Asymptomatic and isolated DLCO alteration has frequently been reported in SLE, but its clinical relevance has not been established. Methods This retrospective study focused on 232 SLE patients fulfilling the 2019 EULAR/ACR classification criteria for SLE. Data were collected from the patient's medical record, including demographic, clinical and immunological characteristics, while DLCO was measured when performing pulmonary function tests as part of routine patient follow-up. Results At the end of follow-up, DLCO alteration (<70% of predicted value) was measured at least once in 154 patients (66.4%), and was associated with a history of smoking as well as interstitial lung disease, but was also associated with renal and neurological involvement. History of smoking, detection of anti-nucleosome autoantibodies and clinical lymphadenopathy at diagnosis were independent predictors of DLCO alteration, while early cutaneous involvement with photosensitivity was a protective factor. DLCO alteration, at baseline or any time during follow-up, was predictive of admission in intensive care unit and/or of all-cause death, both mainly due to severe disease flares and premature cardiovascular complications. Conclusion This study suggests a link between DLCO alteration and disease damage, potentially related to SLE vasculopathy, and a prognostic value of DLCO on death or intensive care unit admission in SLE. [ABSTRACT FROM AUTHOR]

Objectives The direct impact of inflammatory conditions and their therapy with corticosteroids contribute to an increased risk of osteoporosis with associated fractures. Familial Mediterranean fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. Methods A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000 and 2016 and controls was conducted including age- and sex-matched controls in a 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate Cox regression models. Results A total of 9769 FMF patients were followed for a median period of 12.5 years. Of these, 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8, respectively, and a crude hazard ratio of 1.62 (95% CI 1.35, 1.93; P  < 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls [60.1 (s. d. 12.4) vs 62.5 (s. d. 11.0) years; P  = 0.028]. A total of 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3, respectively, and a crude HR of 1.60 (95% CI 1.05, 2.44; P  < 0.05). Conclusion FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients. [ABSTRACT FROM AUTHOR]

Photometric wide-area observations in the next decade will be capable of detecting a large number of galaxy-scale strong gravitational lenses, increasing the gravitational lens sample size by orders of magnitude. To aid in forecasting and analysis of these surveys, we construct a flexible model based on observed distributions for the lens and source properties and test it on the results of past lens searches, including SL2S, SuGOHI, and searches on the COSMOS HST and DES fields. We use this model to estimate the expected yields of some current and planned surveys, including Euclid Wide, Vera Rubin LSST, and Roman High Latitude Wide Area. The model proposed includes a set of free parameters to constrain on the identifiability of a lens in an image, allowing construction of prior probability distributions for different lens detection methods. The code used in this work is made publicly available. [ABSTRACT FROM AUTHOR]

How do we construct our causal directed acyclic graphs (DAGs)—for example, for life-course modeling and analysis? In this commentary, I review how the data-driven construction of causal DAGs (causal discovery) has evolved, what promises it holds, and what limitations or caveats must be considered. I find that expert- or theory-driven model-building might benefit from some more checking against the data and that causal discovery could bring new ideas to old theories. [ABSTRACT FROM AUTHOR]

Sepsis is a leading cause of pediatric mortality and timely antibiotic administration has been shown to improve outcomes. In this retrospective review of a single center sepsis dataset, we identified younger age and female sex as more likely to have delays in antibiotics. [ABSTRACT FROM AUTHOR]

Introduction Recurrent falls are observed frequently among older people, and they are responsible for significant morbidity and mortality. The aim of the present study was to verify sensitivity, specificity and accuracy of World Guidelines for Falls Prevention and Management (WGFPM) falls risk stratification algorithm using data from the Osteoarthritis Initiative (OAI). Methods Participants aged between 40 and 80 years were stratified as 'low risk', 'intermediate risk' or 'high risk' as per WGFPM stratification. Data from the OAI cohort study were used, a multi-centre, longitudinal, observational study focusing primarily on knee osteoarthritis. The assessment of the outcome was carried out at baseline and during the follow-up visit at 24 months. Data about sensitivity, specificity and accuracy were reported. Results Totally, 4796 participants were initially included. Participants were aged a mean of 61.4 years (SD = 9.1) and were predominantly women (58.0%). The population was divided into three groups: low risk (n  = 3266; 82%), intermediate risk (n  = 25; 0.6%) and high risk (n  = 690; 17.3%). WGFPM algorithm applied to OAI, excluding the intermediate-risk group, produced a sensitivity score of 33.7% and specificity of 89.9% for predicting one or more falls, with an accuracy of 72.4%. Conclusion In our study, WGFPM risk assessment algorithm successfully distinguished older people at greater risk of falling using the opportunistic case finding method with a good specificity, but limited sensitivity, of WGFPM falls risk stratification algorithm. [ABSTRACT FROM AUTHOR]

Background High-risk human papillomavirus (HR-HPV) is a known cause of cervical cancer (CC). Latvia has a high incidence of CC compared with the average incidence in the European Union. This study aims to fill the data gap on the HR-HPV burden in Latvia, providing information on its prevalence and associated factors. Methods The cross-sectional study was conducted from February 2021 to April 2022. Participants 25–70 years old visiting a general practitioner (general population) or those referred to a colposcopy clinic with changes in their cervical cytology (colposcopy population) collected vaginal self-sample and completed a paper-based questionnaire. Samples were analyzed with Cobas 6800 System (Roche) for HPV16, HPV18 and other HR-HPV (HPV31/33/35/39/45/51/52/56/58/59/66/68). Descriptive statistics for categorical variables were performed. The Chi-square test was used to determine for the statistical significance of differences in the proportions of the dependent variable between subgroups of the independent variable. Univariate and multivariate binary logistic regression were used to identify factors associated with positive HR-HPV status. Results were considered statistically significant at P  < 0.05. Results A total of 1274 participants provided a valid sample. The prevalence of any HR-HPV infection was 66.8% in the colposcopy group and 11.0% in the general population. Factors associated with positive HR-HPV status were marital status single/divorced/widowed (vs. married/cohabiting) [adjusted OR (aOR) 2.6; P  = 0.003], higher number of lifetime sex partners [aOR 5.1 (P  < 0.001) and 4.0 (P  = 0.001)] for six or more and three to five partners in the general population; in the colposcopy group, the statistical significance remained only for Latvian ethnicity (vs. other) (aOR 1.8; P  = 0.008) and current smoking (vs. never) (aOR 1.9; P  = 0.01). Conclusion We documented a comparison to European Union HR-HPV infection burden in Latvia. Any HR-HPV positivity was significantly associated with sexual and other health behavior. [ABSTRACT FROM AUTHOR]

Objectives Self-compassion has been identified as a psychological resource for aging well. To date, self-compassion among older adults has typically been conceptualized as a trait variable. This study examined whether day-to-day (state) variability in self-compassion was associated with negative affective reactivity to daily stressors. Methods Daily diary assessment methods were used to examine the potential moderating role of between- and within-person self-compassion on the relationship between daily stressors and negative affect. A community-based sample of 107 older adults aged 65+ completed questionnaires once daily over 14 days. Results Multilevel modeling revealed that 37% of the variance in self-compassion occurred within persons. Daily self-compassion moderated the relationship between daily stressor exposure and daily negative affect. On days with greater stressor exposure than usual, older adults showed less negative affective reactivity on days when self-compassion was higher, compared with days when self-compassion was lower. No moderating effects were observed for between-person (trait) self-compassion. Discussion These findings suggest that self-compassion in older adults should be conceptualized as both state and trait variables and that state self-compassion may be protective in the stress–reactivity pathway. Future research should investigate whether brief self-compassion interventions might help older adults to avoid or downregulate negative emotions in response to stressors. [ABSTRACT FROM AUTHOR]

The coronavirus disease (Covid-19) pandemic raised challenges for everyday life. Development of new diagnostic tests was necessary, but under such enormous pressure risking inadequate evaluation. Against a background of concern about standards applied to the evaluation of in vitro diagnostic tests (IVDs), clear statistical thinking was needed on the principles of diagnostic testing in general, and their application in a pandemic. Therefore, in July 2020, the Royal Statistical Society convened a Working Group of six biostatisticians to review the statistical evidence needed to ensure the performance of new tests, especially IVDs for infectious diseases—for regulators, decision-makers, and the public. The Working Group's review was undertaken when the Covid-19 pandemic shone an unforgiving light on current processes for evaluating and regulating IVDs for infectious diseases. The report's findings apply more broadly than to the pandemic and IVDs, to diagnostic test evaluations in general. A section of the report focussed on lessons learned during the pandemic and aimed to contribute to the UK Covid-19 Inquiry's examination of the response to, and impact of, the Covid-19 pandemic to learn lessons for the future. The review made 22 recommendations on what matters for study design, transparency, and regulation. [ABSTRACT FROM AUTHOR]

The marketing of heated tobacco products (HTPs), like IQOS, influences consumers' perceptions. This mixed-methods study analyzed (i) survey data (2021) of 2222 US and Israeli adults comparing perceptions of 7 IQOS attributes (design, technology, colors, customization, flavors, cost and maintenance) and 10 marketing messages (e.g. 'Go smoke-free...') across tobacco use subgroups and (ii) qualitative interviews (n  = 84) regarding IQOS perceptions. In initial bivariate analyses, those never using HTPs (86.2%) reported the least overall appeal; those currently using HTPs (7.7%) reported the greatest appeal. Notably, almost all (94.8%) currently using HTPs also currently used cigarettes (82.0%) and/or e-cigarettes (64.0%). Thus, multivariable linear regression accounted for current cigarette/e-cigarette use subgroup and HTP use separately; compared to neither cigarette/e-cigarette use (62.8%), cigarette/no e-cigarette use (17.1%) and e-cigarette/no cigarette use (6.5%), those with dual use (13.5%) indicated greater overall IQOS appeal (per composite index score); current HTP use was not associated. Qualitative data indicated varied perceptions regarding advantages (e.g. harm, addiction and complexity) of IQOS versus cigarettes and e-cigarettes, and perceived target markets included young people, those looking for cigarette alternatives and females. Given the perceived target markets and particular appeal to dual cigarette/e-cigarette use groups, IQOS marketing and population impact warrant ongoing monitoring to inform regulation. [ABSTRACT FROM AUTHOR]

Mobile mammography units (MMUs) can enhance access to breast cancer screening by providing convenient, cost-effective service, particularly for uninsured and underinsured women. However, prior studies indicate that acceptability concerns about quality and privacy, among other issues, may prevent women from utilizing MMUs. The current study employs a within-participant experimental design exposing participants to messages about different MMU characteristics to determine which characteristics are most effective in persuading them to use an MMU. The study also examined how messaging interacts with participants' ethnic identity to influence outcomes. Data were collected from a diverse sample of uninsured and underinsured women as part of a formative study to promote the utilization of a mobile mammography facility in Central Texas. Results of mixed-effect linear models show that messages about equity, appointment convenience, privacy and comfort, and quality of equipment and staff were rated as more persuasive than messages about convenience of location and language accessibility. However, Hispanic women rated language accessibility higher than other participants did. The results can guide MMU organizers and promotion managers as they determine the best approach to promote mobile mammography services in different communities. [ABSTRACT FROM AUTHOR]

Aims Mitral regurgitation (MR) causes left atrial (LA) enlargement and impaired reservoir function. We assessed whether changes in LA size, strain, and stiffness in significant (moderate or greater) primary MR are sex-specific. Methods and results In the 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study, 111 patients with primary MR were prospectively investigated with 2D and 3D echocardiography. MR was severe if the 3D regurgitant fraction was ≥50%. LA size was assessed by maximum, minimum, and pre-A 3D volume (LAV), mechanics by peak reservoir (LASr) and contractile strain, and stiffness by the ratio: mitral peak E-wave divided by the annular e′ velocity (E/e′)/LASr. Women were older, had higher heart rate, and lower body mass index and MR regurgitant volumes (P < 0.05). 3D LAV indexed for body surface area and LA contractile strain did not differ by sex, while LASr was lower (22.2 vs. 25.0%) and LA stiffness higher in women (0.56 vs. 0.44) (P < 0.05). In linear regression analysis, female sex was associated with higher LA stiffness independent of age, minimum LAV, left ventricular global longitudinal strain, diabetes, and coronary artery disease (R 2 = 0.56, all P < 0.05). In logistic regression analysis, women had a four-fold (95% CI 1.2–13.1, P = 0.02) higher adjusted risk of increased LA stiffness than men. Conclusion Women with significant primary MR have more impaired LA reservoir mechanics and increased LA stiffness compared with men despite lower MR regurgitant volumes and similar indexed LA size. The findings reveal sex-specific features of LA remodeling in MR. Trial Registration ClinicalTrials.gov Identifier: NCT04442828 [ABSTRACT FROM AUTHOR]

Aims To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA). Methods and results Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.39 ± 1.17 years). Out of 202 patients who were analysed in the SMARTool main clinical study, a lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. A quantitative CTA analysis was performed by using a separate core laboratory blinded from clinical data. In the univariable analysis, it was found that no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, it was found that three lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester(20:3), sphingomyelin (SM)(40:3), and SM(41:1) were found to be positively related to non-calcified plaque progression (Bonferroni-adjusted P -values = 0.005, 0.016, and 0.004, respectively). Conclusion The current study showed an independent relationship between specific lipid species determined by a plasma lipidomic analysis and non-calcified coronary plaque progression assessed by a serial, quantitative coronary CTA analysis. [ABSTRACT FROM AUTHOR]

Background Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. Methods Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. Results The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N  = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N  = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N  = 143) demonstrated superior outcomes vs Chemo (N  = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P  = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P  < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P  = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P  < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. Conclusions Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027). [ABSTRACT FROM AUTHOR]

Background This prospective observational study evaluated the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC). A preplanned 2-year final analysis was performed to confirm survival and tumor behavior with nivolumab monotherapy. Patients and Methods The primary endpoint was overall survival (OS). The data regarding tumor size were prospectively collected and evaluated using the RECIST criteria. Exploratory analyses were performed for survival according to the tumor response and depth of response (DpR) in patients with measurable lesions who were receiving nivolumab monotherapy as third- or later-line therapy. Results In 487 patients, the median OS and progression-free survival (PFS) were 5.8 (95% CI 5.3-6.9) months and 1.8 (95% CI 1.7-2.0) months, respectively. The response rate (RR) was 14.5% in 282 patients with measurable lesions. In 234 patients treated with third- or later-line, the DpR was found to be associated with PFS and OS in the Spearman analysis (r  = 0.55 and 0.44, respectively) as well as using a discrete variable. When the DpR was divided into 5 groups (−20%≥DpR; −20%

Background This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. Methods The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. Results Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P  = .370 and.334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. Conclusions For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT. [ABSTRACT FROM AUTHOR]