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Psychometric Properties of the Indonesian Version of Religious Orientation Scale in Muslim Adolescents Sample
Get PDFThis study aimed to validate the Indonesian version of the Religious Orientation Scale (ROS-I), an adaptation of Allport and Ross’s (1967) measure of intrinsic and extrinsic religious orientation, using the Rasch model analysis. ROS-I, which consists of two subscales: Intrinsic Religious Orientation (IRO) and Extrinsic Religious Orientation (ERO) was tested to 410 Muslim adolescents from the Greater Jakarta area using online questionnaire. The psychometric evaluation showed that the ROS-I had good index of person and item separation, unidimensional construct, local independence, good item fit index, and good distributions for its rating scales. Therefore, the ROS-I has generally proven to be a valid and reliable tool for evaluating two aspects of religious orientation in Indonesian Muslim adolescents. However, this study restriction to Muslim adolescents’ population may limit its generalizability that calls for broader and more diverse population for future research. Nevertheless, the validated ROS-I offers a useful assessment of religious orientation in Indonesia and similar cultural settings
The interplay of reward responsiveness and socioeconomic disadvantage in the prospective prediction of depression symptoms in youth
Get PDFBACKGROUND: Alterations in reward responsiveness represent a key mechanism implicated in youth depression risk. However, not all youth with these alterations develop depression, suggesting the presence of factors that may moderate risk patterns. As socioeconomic disadvantage is also related to youth depression risk, particularly for youth exhibiting altered reward function, this study examined whether indices of family- and neighborhood-level disadvantage interacted with electrocortical reward responsivity to predict depression symptom trajectories across childhood and adolescence. METHODS: Participants included 76 youth (ages 9-16 years) at low and high risk for depression based on maternal history of depression. At baseline, youth completed a monetary reward-guessing task while electroencephalography was recorded to measure the reward positivity (RewP), an event-related potential indexing reward responsiveness. Family and neighborhood disadvantage were assessed using the income-to-needs (ITN) ratio and Area Deprivation Index (ADI), respectively. Self-reported and clinician-rated depression symptoms were assessed across a multiwave, 18-month follow-up. RESULTS: RewP interacted with family- and neighborhood-level disadvantage to predict self-reported depression symptom trajectories. Specifically, blunted RewP predicted self-reported depression symptom increases for youth with a lower ITN ratio and higher ADI score. A blunted RewP also predicted clinician-rated depression symptom increases for youth living in neighborhoods with higher ADI scores. CONCLUSIONS: Findings suggest that reduced reward responsiveness is a mechanism implicated in future depression risk among youth, specifically in the context of family- and neighborhood-level socioeconomic disadvantage. Interventions that enhance reward response among youth exposed to higher levels of socioeconomic disadvantage may be particularly effective in preventing depression emergence
Genomic surveillance uncovers regional variation in HCV transmission networks in rural United States
Get PDFHepatitis C virus (HCV) remains a public health concern in the United States, particularly in rural communities where the opioid epidemic accelerates transmission among people who use drugs (PWUD). Despite this growing burden, the genetic features and transmission dynamics of HCV in these settings are poorly understood. We analyze 692 HCV antibody-positive specimens collected from rural communities in ten U.S. states using amplicon-based deep sequencing and the Global Hepatitis Outbreak and Surveillance Technology (GHOST) platform to reconstruct transmission networks. Among sequenced individuals, 29.5% are linked within clusters. Cluster structure varies by region from sparse networks in Ohio to dense clusters in New England and phylogenetic analyses show that some networks persist for over a decade, indicating sustained transmission. Nearly half of all clusters involve individuals connected through social recruitment, suggesting peer-referral strategies effectively identify transmission chains. Penalized regression retains only a few individual factors including younger age, peer or partner recruitment, illegal income, methamphetamine use, each with modest effects. These findings suggest that clustering is shaped primarily by social and structural contexts rather than individual characteristics and underscore the importance of integrating genomic surveillance with social-network insights to detect emerging HCV clusters and guide targeted interventions in underserved rural communities
Pediatric Thyroid Cancer Multidisciplinary Team Improves Adherence of Radioactive Iodine Treatment According to National Guidelines
Get PDFOBJECTIVE: To evaluate whether a multidisciplinary team (MDT) approach improves adherence to the 2015 American Thyroid Association (ATA) postoperative surveillance guidelines in pediatric thyroid cancer patients. METHODS: A retrospective review at our institution was performed on pediatric patients who had thyroidectomy for papillary or follicular thyroid cancer between 2017 and 2024. Patients who were treated from 2017 to 2020 (pre-MDT) were compared to those treated from 2021 to 2024 (post-MDT), following the establishment of the MDT in January 2021. Data collected included timing of postoperative thyroglobulin (Tg) tests, iodine-123 (123I) diagnostic scans, iodine-131 (131I) administration, and the number of endocrinologists involved in care. RESULTS: From 2017 to 2024, 47 patients were identified (n = 28 from 2017 to 2020; n = 19 from 2021 to 2024). Median age was 15 years. 131I was administered in 47% of low-risk patients from 2017 to 2020 (n = 7/15) and in 0% of low-risk patients from 2021 to 2024 (n = 0/7) (P = .04) based on ATA guidelines. Between the two time periods, there was an increased percentage of patients who had postoperative Tg tests or 123I diagnostic scans according to the ATA guidelines. DISCUSSION: There were significantly fewer low-risk patients who received 131I treatment in the 2021 to 2024 group compared to the 2017 to 2020 group. A greater proportion of patients received guideline-recommended postoperative test in the second time period. Introduction of the MDT and fewer endocrinologists involved in postoperative care of each patient from 2021 is associated with improved adherence to the ATA guidelines for pediatric thyroid cancer patients. IMPLICATIONS FOR PRACTICE: Our study supports the importance of the MDT in the postoperative care of pediatric thyroid cancer patients
A gene-based model of fitness and its implications for genetic variation: Linkage disequilibrium
Get PDFA widely used model of the effects of mutations on fitness (the “sites” model) assumes that heterozygous recessive or partially recessive deleterious mutations at different sites in a gene complement each other, similarly to mutations in different genes. However, the general lack of complementation between major effect allelic mutations suggests an alternative possibility, which we term the “gene” model. This model assumes that a pair of heterozygous deleterious mutations in trans behave effectively as homozygotes, so that the fitnesses of trans heterozygotes are lower than those of cis heterozygotes. We examine the properties of the two different models, using both analytical and simulation methods. We show that the gene model predicts positive linkage disequilibrium (LD) between deleterious variants within the coding sequence under conditions when the sites model predicts zero or slightly negative LD. We also show that focussing on rare variants when examining patterns of LD, especially with Lewontin’s D´ measure, is likely to produce misleading results with respect to inferences concerning the causes of the sign of LD. Synergistic epistasis between pairs of mutations was also modeled; it is less likely to produce negative LD under the gene model than the sites model. The theoretical results are discussed in relation to patterns of LD in natural populations of several species
The exposure potential restriction rule revisited
Get PDFThere are people who cannot receive certain treatments or experience certain exposures. For example, people without a uterine cervix cannot receive an intrauterine device. This lack of exposure potential in some persons instigated an interesting discussion in the 1980s regarding whether such persons should be included in case–control studies. A recommendation to exclude them was named the exposure potential restriction rule. We consider this rule in the context of current modern epidemiology and causal inference including clearly defining which causal questions can be answered with which assumptions, how exposure potential relates to the positivity assumption, how the exposure potential restriction rule may amplify uncontrolled confounding when the reason for a lack of exposure potential is an instrumental variable and the complementary idea of exposure compulsion. Using a simple simulation, we demonstrate that both restricting and not restricting on a variable that defines lack of exposure may induce bias depending on the causal structure. Therefore, careful thought must be used when deciding whether to remove participants who have no potential to be exposed or no potential to be unexposed
High-throughput cytological profiling uncovers genotype-phenotype associations in Mycobacterium tuberculosis clinical isolates.
Get PDFUnderstanding the functional impact of bacterial genetic diversity is crucial for linking pathogen variants to clinical outcomes. Here, we introduce a high-throughput cytological profiling pipeline optimized for Mycobacterium tuberculosis (Mtb) clinical strains, integrating OD-calibrated feature analysis and high-content microscopy. Our system quantifies single-bacterium morphological and physiological traits related to DNA replication, redox state, carbon metabolism, and cell envelope dynamics. Applied to 64 Mtb clinical isolates from lineages 1, 2, and 4, the approach revealed that cytological phenotypes recapitulate genetic relationships and exhibit both lineage- and density-dependent dynamics. Notably, we identified a link between a convergent "small cell" phenotype and a convergent ino1 mutation that is associated with the presence of an antisense transcript, suggesting a potential non-canonical regulatory mechanism under selection. In summary, we present a resource-efficient approach for mapping Mtb's phenotypic landscape, uncovering cellular traits that underlie its evolution and providing new insights into the functional consequences of bacterial genetic diversity. IMPORTANCE: Understanding how genetic variation in Mycobacterium tuberculosis (Mtb) shapes its physical traits is essential to unraveling the evolution of this global pathogen. Here, we introduce a systematically optimized, high-throughput imaging platform for the comprehensive characterization of Mtb clinical strains. We demonstrate that Mtb's phenotypic manifestation is shaped by both genetic background and culture density. By accounting for these factors, our analysis linked distinct cellular dynamics to specific lineages, sublineages, and even single nucleotide variations. Notably, we linked a recurring mutation to a unique cell-shortening phenotype, finding that it potentially acts by creating a cryptic antisense transcript. This platform provides a powerful framework for systematically dissecting the physiological dynamics underlying Mtb evolution and identifying new therapeutic vulnerabilities of this deadly pathogen
Expanding cholera serosurveillance to vaccinated populations.
Get PDFMass oral cholera vaccination campaigns targeted at subnational areas with high incidence are central to global cholera elimination efforts. Serological surveillance offers a complementary approach to address gaps in clinical surveillance in these regions. However, similar immune responses from vaccination and infection can lead to overestimates of the incidence of infection. To address this, we analyzed antibody dynamics in infected and vaccinated individuals to refine seroincidence estimation strategies for partially vaccinated populations. We tested 757 longitudinal serum samples from confirmed Vibrio cholerae O1 cases and uninfected contacts in Bangladesh as well as vaccinees from Bangladesh and Haiti, using a multiplex bead assay to measure IgG, IgM, and IgA binding to five cholera-specific antigens. Infection elicited stronger and broader antibody responses than vaccination, with rises in cholera toxin B-subunit (CTB) and toxin-coregulated pilus A (TcpA) antibodies uniquely associated with infection. Previously proposed random forest models frequently misclassified vaccinated individuals as recently infected (over 20% at some time points) during the first 4 months post-vaccination. To address this, we developed new random forest models incorporating vaccinee data, which kept false-positive rates among vaccinated (1%) and unvaccinated (6%) individuals low without a significant loss in sensitivity. Simulated serosurveys demonstrated that unbiased seroincidence estimates could be achieved within 21 days of vaccination campaigns by ascertaining the vaccination status of participants or applying updated models. These approaches to overcome biases in serological surveillance enable reliable seroincidence estimation even in areas with recent vaccination campaigns enhancing the utility of serological surveillance as an epidemiologic tool in moderate-to-high cholera incidence settings. IMPORTANCE: Serological surveillance can improve how we monitor cholera in high-burden areas where clinical surveillance is limited. However, vaccination can produce immune responses similar to infection, leading to overestimates in seroincidence. This study extends seroincidence estimation techniques using machine learning models to partially vaccinated populations. We analyzed antibody dynamics from vaccinated and infected individuals to develop methods that reduce the misclassification of vaccinated individuals as recently infected. These methods enable reliable seroincidence estimates in areas with recent vaccination campaigns, providing a step toward better epidemiologic monitoring in the context of global cholera control initiatives. Studies in other populations are needed to further validate our results and understand their generalizability
Association between neutrophil to lymphocyte ratio and Alzheimer's disease in large biobank cohorts.
Get PDFBackground Neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.ObjectiveThe objective of this study is to assess the association between NLR and AD as a biomarker or potential causal step for AD pathogenesis.
Methods Cohorts used for analysis include the UK Biobank (n = 207100; n = 2198 AD cases) and the All of Us research program (AoU, n = 45202; n = 263 AD cases) which allowed for a larger sample size than most previous studies. Cox proportional hazard models were used to assess the association between NLR and AD, including in models adjusting for factors in the UK Biobank Dementia Risk Score. A Mendelian randomization analysis was performed to assess the potential causality between NLR and AD.
Results NLR was associated with AD in the UK Biobank (HR: 1.03 per 1 SD, 95% CI: 1.01-1.05) but not in AoU (HR: 1.02, 95% CI: 0.92-1.14). A fixed effects model resulted in a pooled HR: 1.03 (95% CI: 1.02-1.05). These effects were robust to adjustment for C-reactive protein, APOE ε4 genotype status, APOE ε2 genotype status, and other AD risk factors. The MR analysis was performed with 214 NLR-associated variants but was not significant (IVW estimate: -0.001, p: 0.99).
Conclusions Findings provide evidence for NLR as a biomarker for AD but not as a causal risk factor
Outcomes after surgical fixation of lower extremity fractures in patients with chronic kidney disease
Get PDFAssess mortality and complications in patients with chronic kidney disease (CKD) after fixation of lower extremity fractures. Retrospective cohort. Single academic level 1 trauma center. Four hundred seventy-six patients with CKD and operative lower extremity fractures (pelvis to ankle). Patients were grouped according to preoperative glomerular filtration rate (GFR) per the National Kidney Foundation Guidelines. Patients with moderate-to-severe CKD and end stage renal disease (ESRD) were compared with those with predisease state CKD. Mortality and complication rates at time points up to 2 years or until death. Patients with predisease state CKD were significantly less likely to have a complication within 2 years than patients with ESRD but not patients with moderate-to-severe CKD. One-year and 2-year mortality rate were significantly higher in the moderate-to-severe CKD (36.1%) and ESRD (49.0%) groups than in the predisease state CKD group. Compared to the patients with predisease state CKD, patients with moderate-to-severe CKD and ESRD both had increased odds of 1-year mortality, 2-year mortality, and a complication at 2 years after operative fixation of a lower extremity fracture. Patients with ESRD also had increased odds of 30-day and 90-day mortality compared with patients with predisease state CKD. Compared to patients with predisease state CKD, patients with moderate-to-severe CKD and ESRD had increased odds of 1-year mortality and 2-year mortality, as well as a complication at 2 years. Patients with ESRD had increased odds of 30-day and 90-day mortality compared with patients with predisease state CKD. Two-year mortality rate was 49% in the ESRD group. Therapeutic level III