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A Study on the Risk Behaviour Among Street-Connected Children in the Kuala Lumpur, Malaysia: Antecedents Factors and Primary Intervention
No full textStreet life often forced street-connected children to engage in the risk behaviour. A prolonged and persistent exposure to the street environment facilitates this process and affects their development. This study aims to explore the involvement of street-connected children in risky behaviour, influence factors of street-connected children in risky behaviour and suggest interventions to reduce the involvement of street-connected children in risky behaviour. Purposive sampling techniques were employed to collect information from N = 303 street-connected children aged 9 to 17 years. Descriptive statistics, Pearson correlation, and multiple regression analysis have been employed to analyse the data. Findings show that the involvement of street-connected children in risky behaviour was influenced by peers. Meanwhile, parents working status, educational barriers, housing environment, emotional and psychological wellbeing, and life experience with school were not significant factors in their involvement in risky behaviour. The study contributes develop interventions for street-connected children to mitigate their involvement in risky behaviour, as well as to inform social worker and social provider to improve the health behaviour of these children’s. street-connected children, risky behaviour, homeless, children, antisocial, interventio
Beyond NACC's Uniform Data Set for cognition: the impact of additional items on measurement precision
No full textIntroduction: We sought to determine the implications of integrating additional cognitive test items beyond the items of the Uniform Data Set (UDS) administered by Alzheimer's Disease Research Centers (ADRCs).
Methods: We considered the UDS 1&2 and UDS 3 cognitive batteries alone ("UDS-only") and compared them to batteries augmented with additional items ("UDS-augmented") administered by the University of Pittsburgh, ADRC. We used confirmatory factor analyses to co-calibrate and harmonize three cognitive domains (memory, executive functioning, and language). Then we compared the UDS-only and UDS-augmented with respect to measurement precision, sample sizes required to detect 25% differences in rates of decline, and association between baseline scores and the hazard of converting from mild cognitive impairment to AD dementia.
Results: UDS-augmented substantially enhanced measurement precision across all cognitive domains for UDS 1&2 and UDS 3.
Discussion: There is substantial value in integrating item content beyond the UDS.
Highlights: We considered items from the UDS 1&2 and UDS 3 cognitive batteries alongside augmented site-specific content for the memory, executive functioning, and language domains. Augmented scales improved measurement precision in each case. As expected, improved measurement precision facilitated better performance for each scale. It would be useful to integrate multiple sources of cognitive data into comprehensive estimates of domain performance
Health Equity Leadership and Mentoring (HELM): A health equity-focused early-career development program to promote biomedical workforce diversity
No full textIntentionally enhancing and supporting the early careers of individuals from populations underrepresented in science and medicine (URSM) is essential to achieving health equity. The Health Equity Leadership and Mentoring (HELM) Program at the University of Minnesota and the University of Utah is designed to foster academic excellence and build leadership capacity of postdoctoral fellows, clinical fellows, and early-career faculty who identify as URSM and/or who are committed to careers in health equity research and clinical care. HELM models a culture of psychosocial safety to create a sense of belonging and uses evidence-based and culturally aware mentoring and career development strategies with the goal of retaining diverse faculty. HELM proved agile and adaptive during the Covid-19 pandemic and has been successful in states with and without legislation limiting diversity programs. Across the 2 institutions, the HELM program has supported over 200 trainees and early-career faculty through mid-2024. Among HELM participants who joined the program as faculty, 85%-95% have remained in their faculty positions
Automatic segmentation of clear cell renal cell carcinoma based on deep learning and a preliminary exploration of the tumor microenvironment
No full textBackground: Whole-slide imaging (WSI) is increasingly becoming a standard method for diagnosing clear cell renal cell carcinoma (ccRCC). This advanced imaging technique allows for high-resolution examination of tissue sections, improving diagnosis and management of renal cancers. Immunotherapy has emerged as an effective treatment for tumors; however, the differential characteristics of the tumor microenvironment (TME) significantly influence therapeutic outcomes. Understanding the interactions between cancer cells and the TME is essential for optimizing immunotherapeutic strategies. This study aims to investigate the characteristics of the TME in ccRCC using WSI, with the goal of identifying factors that might influence immunotherapy response and improving therapeutic strategies.
Methods: In this study, we proposed a novel method for the automatic segmentation of ccRCC regions based on deep-learning techniques. This method uses advanced convolutional neural networks to effectively distinguish between tumor areas (TAs) and surrounding tissues. Additionally, we employed inverse threshold segmentation to quantitatively analyze the results and spatial distributions of lymphocytes and collagen fibers in immunohistochemical and Masson's trichrome-stained images. This comprehensive approach not only streamlines the diagnostic process but also enhances the precision of histopathological assessments.
Results: Our model had a classification accuracy of 96.67% on image patches and a sensitivity of 94.29%, demonstrating its ability to segment TAs both accurately and efficiently. The distribution of cluster of differentiation (CD)3+ and CD8+ T lymphocytes, and collagen fibers in patients at different tumor-node-metastasis (TNM) stages was analyzed. The results revealed that a high infiltration of CD3+ T cells, particularly CD8+ cytotoxic T cells, was more prevalent in patients with advanced-stage tumors. Additionally, the proliferation of collagen fibers in tumors was found to be significantly correlated with tumor growth and metastasis.
Conclusions: Our results underscore the potential of artificial intelligence (AI) technology to provide novel insights to guide ccRCC immunotherapy. By applying deep learning to tumor segmentation and TME analysis, this methodology offers a promising approach to improve the understanding of tumor biology and therapeutic outcomes. Future research should focus on integrating these findings into clinical practice to optimize patient-specific immunotherapeutic strategies, and thus advance treatment protocols and improve the survival rates of ccRCC patients
Discovery Pipeline for AKI: Molecules, Mechanisms, Models, and Targets
No full textBackground: Acute kidney injury (AKI) represents a multifaceted clinical syndrome marked by precipitous loss of kidney function, high morbidity and mortality, and a strong propensity for progression to chronic kidney disease. Collectively, these challenges underscore the imperative to delineate conserved molecular and signaling networks that are uniformly engaged across diverse AKI etiologies.
Summary: Herein, we survey five emerging research domains poised to transform AKI pathophysiology and therapeutic paradigms. First, lymphatic network remodeling has been implicated as a critical determinant of renal immunodynamics and interstitial fluid homeostasis, whereby modulation of VEGF-C/D signaling reshapes immune cell trafficking and fibrogenic responses. Second, we will cover emerging evidence that positions macrophage ferritin heavy chain as a key regulator of macrophage phenotype and subsequent kidney ferroptosis susceptibility via coordinated regulation of synuclein-⍺, and Spic. Third, we will emphasize incorporating development as a biological variable into experimental design based on evidence that identifies age-dependent divergences in injury susceptibility, and progression of disease. Fourth, we cover mechanosensitive ion channels that are activated by therapeutic ultrasound offering novel opportunities to harness the cholinergic anti-inflammatory pathway for nephroprotection. Finally, targeting tubular epithelial cell senescence and mitochondrial bioenergetics as a promising approach to limit progression of kidney disease will be discussed.
Key messages: Collectively, these emerging mechanisms deepen our understanding of AKI pathophysiology and unveil novel therapeutic targets with the potential to transform the treatment landscape
HDL Cholesterol Is Remarkably Cardioprotective Against Coronary Artery Disease in Native Hawaiians and Pacific Islanders
No full textBackground: High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiometabolic risk and exhibits nonlinear effects at extreme levels. Cardiometabolic diseases are a leading cause of death and are particularly prevalent among Native Hawaiian and Pacific Islanders (NHPIs).
Objectives: This study characterizes HDL-C's association with coronary artery disease (CAD), major adverse cardiovascular events (MACE), and type 2 diabetes (T2D) in NHPIs compared to the general population.
Methods: Using electronic health record data from the National Institutes of Health All of Us Research Program, we applied Cox proportional hazards models to compare HDL-C's protective effects on CAD, MACE, and T2D between 261 NHPIs and the remaining cohort (n = 188,802). Models were adjusted for key confounders, and restricted cubic splines were used to assess nonlinear risk dynamics.
Results: Tracking individuals across 10,534,661 person-years (mean age 55.7 ± 15.8 years, 38% male), HDL-C was more strongly associated with reduced CAD risk in NHPIs (HR: 0.32; 95% CI: 0.19-0.54) than in the general cohort (HR: 0.57; 95% CI: 0.56-0.58). A marginally stronger association was observed for MACE (NHPI HR: 0.40; 95% CI: 0.23-0.71 vs general HR: = 0.54; 95% CI: 0.53-0.56), while T2D associations were similar. Spline analysis indicated that low HDL-C increases risk for both CAD and T2D in NHPIs.
Conclusions: HDL-C's protective role against cardiometabolic diseases is more pronounced in NHPIs, particularly for CAD. These findings support further investigation into tailored clinical assessments for this population
Exploring Centiloid Robustness: Impact of Sample Size and Image Resolution on Centiloid Conversion Accuracy
No full textAs Centiloids are increasingly used in trials and clinical settings to quantify amyloid-β (Aβ) PET, better characterization of sources of measurement error is essential. We examined 2 potential factors driving it: variability in the estimated coefficients in the SUV ratio-to-Centiloid conversion equation related to random sampling of the calibration dataset and PET image resolution. Methods: First, we analyzed [11C]PiB scans in 200 participants with a clinical diagnosis of Alzheimer disease (cAD) and 114 Aβ-negative participants. PET scans were processed using the standard Centiloid pipeline and a nonstandard MRI-based pipeline (native space, cerebellar cortex as reference). We split data into training and test datasets (n = 157 each) to compare conversion equations in subsamples with an n of 10-30 Aβ-negative and 15-50 cAD participants. Second, all [11C]PiB images, along with 604 [18F]florbetaben and 538 [18F]florbetapir images, were reduced from high (6/7 mm3) to medium (8 mm3) and low (10 mm3) resolution and resulting Centiloids were compared between resolutions. rPOP and CapAIBL, 2 PET-only processing pipelines, were used to explore the effects of the PET spatial resolution across different pipelines. Results: In the smallest required sample of 15 cAD and 10 Aβ-negative participants, conversion error was 1.7 Centiloids at 25 Centiloids and 3.4 Centiloids at 100 Centiloids. Error decreased to 1.0 Centiloid at 25 Centiloids and 2.0 Centiloids at 100 Centiloids, when including 50 cAD and 30 Aβ-negative participants. Lower image resolution was associated with a systematic difference in Centiloids, especially in highly positive [11C]PiB scans: a scan estimated as 100 Centiloids in high resolution was quantified as 94.2 Centiloids and 84.9 Centiloids at medium and low resolution. When a [11C]PiB scan was quantified as 25 Centiloids in its high resolution, lowering its resolution resulted in reduced values of 23.5 Centiloids and 20.6 Centiloids for medium and low resolution, respectively. Similar trends were observed for [18F]florbetaben and [18F]florbetapir scans. Conclusion: A relatively accurate SUV ratio-to-Centiloid conversion equation for level 2 analyses can still be achieved with a minimally required datasets. Increasing the number of cAD participants reduced error at higher values, whereas adding Aβ-negative participants had little effect. Image resolution significantly impacts Centiloids in highly positive scans and should be considered when interpreting data acquired with different settings. Errors remain minimal at 25 Centiloids, the typical cutoff for determining Aβ positivity
Trends in Treatment of Severe Haemophilia and Impact on Inhibitor Assessment by the EUHASS Registry
No full textBackground: The last 15 years have seen new extended half-life (EHL) recombinant FVIII/IX concentrates and nonreplacement therapy for haemophilia A (emicizumab) introduced in Europe. These changes affect FVIII/IX exposure in previously untreated patients (PUPs) and previously treated patients (PTPs) with severe haemophilia A and B (SHA and SHB) and may modify inhibitor development and/or detection.
Aim: To report trends in treatment for severe haemophilia and concomitant changes in inhibitor incidence.
Methods: Between 2008 and 2022, 97 centres reported inhibitor development against FVIII/IX concentrates to the European Haemophilia Safety Surveillance System (EUHASS). Inhibitors were reported quarterly, and PUPs without inhibitor development annually. Cumulative inhibitor incidences (95% confidence intervals [CI]) were calculated for PUPs and incidence rates/1000 years (CI) for PTPs.
Results: By 2022, SHA-PUPs (n = 1574) received emicizumab (44%), SHL-rFVIII (21.5%), pdFVIII (17.5%) and EHL-rFVIII (17%). SHB-PUPs (n = 236) received EHL-rFIX (79%) and SHL-rFIX (21%). SHA-PTPs (68,772 years) received EHL-rFVIII (31%), SHL-rFVIII (28%), emicizumab (25%), and pdFVIII (15%). SHB PTPs (11,185 years) received EHL-rFIX (69%), pdFIX (15%) and SHL-rFIX (15%). Observed Inhibitor incidence in SHA-PUPs decreased from 24% before 2016 to 6% in 2022 (p < 0.001), and potentially in SHB-PUPs too (from 9% to 3%; p = 0.066), but remained stable in SHA/SHB PTPs.
Conclusion: In 2022, 44% of SHA-PUPs and 25% of SHA-PTPs received emicizumab prophylaxis. Concomitantly, observed inhibitor incidence reduced to 6% in SHA-PUPs. In SHB, EHL-rFIX treatment increased to 79% in SHB-PUPs and 69% in SHB-PTPs. Assessing inhibitor incidence for new concentrates is likely to be hampered by novel treatments causing delayed exposure to FVIII/FIX
Public Policy and Wealth Concentration in Brazil in Declining Workers Rights
No full textPresentation to the International Seminary on Public Policy. Portuguese title: "Politicas publicas de emprego e renda no contexto de concentracao de renda e destruicao dos direitos de trabalho
Association Between Anxiety, Depression, and Opioid Use Disorder in Adult Surgical Patients: A Real-World Data Study
No full textBackground/Objective:
The opioid crisis remains a central issue in public health. Prior research has explored how postoperative opioid prescribing contributes to the development of opioid use disorder (OUD). Pre-existing psychiatric conditions may influence postoperative misuse of opioid medications, but existing research on this association is limited in scope and generalizability. This study aimed to evaluate whether a diagnosis of depression and/or anxiety is associated with increased odds of OUD among adult patients undergoing common opioid-prescribing surgical procedures.
Methods:
In this retrospective case-control study, we used de-identified Electronic Health Record data from the IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights) Psychiatric database. Adult patients aged 18-70 who underwent a common opioid-prescribing surgical procedure were identified using CPT codes. Psychiatric and OUD diagnoses were identified using ICD-10 codes. Patients were grouped based on the presence or absence of an OUD diagnosis. Odds ratios were calculated to assess the association between OUD and prior diagnosis of anxiety, depression, or both.
Results:
Among 18,440 patients who underwent a qualifying surgery, 653 were diagnosed with OUD. Of these, 288 had depression, 280 had anxiety, and 223 had both diagnoses, indicating substantial overlap between conditions. Patients with depression (OR: 1.91; 95% CI: 1.63-2.23), anxiety (OR: 1.26; 95% CI: 1.08–1.48), and both conditions (OR: 3.84; 95% CI: 3.24–4.54) had significantly higher odds of OUD compared to surgical patients with other psychiatric diagnoses.
Conclusion and Clinical Implications:
These findings suggest that adult surgical patients with a history of anxiety and/or depression have increased odds of developing OUD. This underscores the clinical importance of individualized pain management and enhanced perioperative support for patients with psychiatric comorbidities. Future research should explore these associations in broader and more diverse populations and evaluate interventions that integrate mental health screening into preoperative planning