Health Science Reports
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Preprints posted in the last 7 days, ranked by how well they match Health Science Reports's content profile, based on 11 papers previously published here. The average preprint has a 0.06% match score for this journal, so anything above that is already an above-average fit.
Tefera, B.; Ali, R.; Megersa, B. S.; Girma, T.; Friis, H.; Abera, M.; Belachew, T.; Olsen, M. F.; Filteau, S.; Wells, J. C.; Wibaek, R.; Yilma, D.; Nitsch, D.
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Introduction Glomerular filtration rate (GFR) is invasive to measure. Therefore, in clinical care, estimated GFR is derived from serum levels of endogenous filtration markers such as creatinine and cystatin C. Multiple studies from high income countries showed differences between estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr). This study aimed to assess the agreement between eGFRcys and eGFRcr in Ethiopian children and identify factors influencing higher eGFRcys and eGFRcr. Method We studied 350 Ethiopian children who were part of the iABC birth cohort study. At the recent follow-up (average age 10 years), serum cystatin C and creatinine were measured. Formulas by Berg (2015) and Hoste (2014) were used to estimate eGFRcys and eGFRcr, respectively, and Bland-Altman plots assessed their agreement. The difference in eGFR (eGFRdiff) was calculated and categorized as less than -15 mL/min/1.73 m2 (higher eGFRcr), between -15 and <15 mL/min/1.73 m2 (concordant), and greater than or equal to 15 mL/min/1.73 m2 (higher eGFRcys). Multinomial logistic regression was used to identify factors associated with higher eGFRcr and higher eGFRcys. Result Estimated glomerular filtration rate (eGFR) showed significant variation based on the estimation formula used. When using formulas by Berg (2015) and Hoste (2014), the median (IQR) eGFRcys and eGFRcr were 99.4 (90.0; 114.1), and 123.2 (110.3; 143.8) mL/min/1.73 m2, respectively. Overall, we observed a poor agreement between eGFRcys and eGFRcr, with only 94 (27.6%) children having concordant results compared to 220 (64.7%) with higher eGFRcr and 26 (7.6%) with higher eGFRcys. If the eGFRcys results are considered reliable, 27.5% of the children had eGFR below 90 mL/min/1.73 m2. Conclusion There was very marked variation in the distributions of estimated eGFRs depending on which formulas for children were used. Agreement between eGFR estimated using cystatin C and creatinine was poor among Ethiopian children. Relative to eGFRcys, kidney function may be overestimated by creatinine-based equation as up to 30ml/min in Ethiopia. Ideally, a validation study with GFR measured by gold standard methods (Inlulin clearance) among children is required. However, because of its invasive nature and financial concerns, Iohexol clearance studies are recommended.
Tesfaye Guteta, E.; Diriba, A.; Tesfaye, K.; Kedir, E.; Wakgari, M.; Jabessa, D.; Chali, M.; Biyena, K.; Sileshi, G.; Jobir, G.
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From 2021 to 2025, MRSA emerged as a major multidrug-resistant pathogen in the study area. Among 545 S. aureus isolates, 67.2% were MRSA, disproportionately affecting children under five (26.5%) and males (55.5%). Case incidence more than doubled by 2025, suggesting rising transmission or resistance. Most isolates were hospital-associated (85.2%), predominantly from outpatients (88.5%), with middle ear discharge as the main source (67%). Gentamicin showed the highest susceptibility (72.1%), while penicillin G resistance was nearly universal (96.7%). The majority (93.4%) were multidrug-resistant, with high MARI values indicating widespread and likely inappropriate antibiotic use. These findings reflect a complex interplay between pathogen behavior, antimicrobial use, and healthcare practices. Increasing MRSA burden may stem from inadequate infection control, poor stewardship, or enhanced community transmission. Incorporating molecular typing could deepen understanding of strain diversity and resistance mechanisms to guide targeted interventions
Okolo, C. C.; Amole, T. G.
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Background The microbial aetiology of early childhood caries (ECC) in sub-Saharan African populations remains poorly characterised, with most studies focusing on conventional cariogenic pathogens like Streptococcus mutans. This study aimed to characterise the salivary microbial profile of children with ECC in urban Kano, northern Nigeria. Methods In this cross-sectional study of 162 children aged 3-5 years in urban Kano, unstimulated saliva samples were collected and analysed using standard bacteriological culture methods. Caries status was assessed using decayed, missing, and filled teeth (dmft) index and International Caries Detection and Assessment System (ICDAS). Microbial isolates were identified through Gram staining, colony morphology, and biochemical tests (catalase, coagulase, oxidase). Results Of 32 microbial isolates obtained, Staphylococcus aureus was the most prevalent (43.8%, n=14), followed by Streptococcus species (28.1%, n=9), Klebsiella species (12.5%, n=4), non-aureus staphylococci (6.3%, n=2), yeast (6.3%, n=2), and Pseudomonas species (3.1%, n=1). Only one isolate demonstrated direct association with dmft-detectable caries. Polymicrobial colonisation occurred in four cases (12.5%), predominantly featuring S. aureus-yeast combinations (n=2). White spot lesions (ICDAS 1-2) were associated with S. aureus and Klebsiella species in two separate cases. Conclusion This study reveals an unexpected predominance of S. aureus in the salivary microbiome of children in northern Nigeria, challenging conventional paradigms of ECC microbiology. The low correlation between microbial isolates and clinical caries suggests complex, multifactorial aetiology. These findings highlight the need for molecular characterisation of oral microbiomes in African populations and reconsideration of caries pathogenesis models in this unique epidemiological context.
Corlis, J.; Bollinger, L.; Mangenah, C.; Ncube, G.; Marake-Raleie, N.; Soothoane, R.; Gwavava, E.; Yemeke, T.; Eichleay, M.; Kapuganti, S.; Stegman, P.; Bellows, N.; Kripke, K.
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Because of its recent regulatory approval in southern and eastern Africa, CAB PrEP represents a scientific advancement with unknown implementation costs in most African countries. To our knowledge, this paper is the first study comparing PrEP costs in health facilities where clients had a choice between three PrEP methods. We collected and analyzed the direct service delivery costs for each method using the same costing approach and assumptions at three facilities in Lesotho and six facilities in Zimbabwe. On average, in Lesotho, the direct costs of providing CAB PrEP were $57.22 for an initiation visit and $54.20 for a refill visit (same PrEP product dose dispensed in both visit types), while the direct costs of oral PrEP were $22.47 (initiation visit with one month of PrEP dispensed) and $31.98 (refill visit dispensing a three-month dose of medication), and the direct costs of the dapivirine ring were $34.27 (initiation visit with one month of PrEP dispensed) and $50.70 (refill visit dispensing a three-month supply). In Zimbabwe, the average per-visit direct costs to provide CAB PrEP were $48.26 (initiation visit) and $47.40 (refill visit), to provide oral PrEP were $13.47 (initiation visit with one month of PrEP dispensed) and $21.78 (refill visit dispensing a three-month dose), and to provide the dapivirine ring were $42.56 (refill visit dispensing a three-month supply). Initiation visits for the dapivirine ring were not observed in Zimbabwe. At a time when national governments are creating budgets for the HIV response with decreased financial support from bilateral and multilateral partners, this paper will inform HIV prevention planning by providing critical client-level data from the healthcare provider perspective.
Bartal, A.; Allouche-Kam, H.; Elhasid Felsenstein, T.; Dassopoulos, E. C.; Lee, M.; Edlow, A. G.; Orr, S. P.; Dekel, S.
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Objective: Posttraumatic stress disorder (PTSD) after a traumatic birth is a serious but overlooked maternal morbidity, affecting ~20% of women following medically complicated deliveries. PTSD can undermine maternal caregiving. Rapid screening tools suited to busy obstetric settings are lacking. We developed and evaluated a brief screener, derived from the 20-item PTSD Checklist for DSM-5 (PCL-5), to identify PTSD related to childbirth. Study Design: We enrolled 107 women with traumatic childbirth. Participants completed the PCL-5 and the gold-standard clinician diagnostic interview for PTSD (CAPS-5); depression was measured with the Edinburgh Postnatal Depression Scale (EPDS). Bootstrap resampling with LASSO regression identified PCL-5 items most associated with PTSD. Firth logistic regression models estimated diagnostic accuracy. Sensitivity, specificity, area under the ROC curve (AUC), and Youden's J statistic determined performance and optimal cut-off. Results: A six-item version of the PCL-5 (PCL-5 R6), statistically derived from the full scale, showed excellent discrimination for PTSD compared with clinician evaluation (AUC = 0.95; 95% CI, 0.89-1.00). A cut-off score of 7 yielded high sensitivity (0.96) and good specificity (0.83), with an overall diagnostic efficiency of 0.86, detecting most PTSD cases while minimizing false positives. The PCL-5 R6 correlated moderately with the EPDS (rho = 0.53), showing that a depression screen alone cannot reliably detect PTSD. Conclusions: A short, 6-item PCL-5 provides a valid, efficient tool for detecting childbirth PTSD. Its brevity and accuracy make it practical for integration into routine postpartum care, enabling timely mental health screening.
Clay, J. M.; Lawrence, K. W.; Johal, P. K.; Sherk, A.; Stockwell, T.; Naimi, T.
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Objective: Minimum unit pricing (MUP) aims to reduce use of cheap, high strength alcoholic beverages that drive harm, yet concerns remain about inequitable effects for structurally vulnerable groups. As part of the Costs, Harms, Expenditures and Alcohol Prices (CHEAP) study, we linked individual-level, product-specific alcohol consumption data from a customized survey with provincial retail price data to estimate prices per standard drink (PPSD) and examine their association with alcohol-related outcomes across sociodemographic groups. Method: A cross-sectional survey of past-week drinkers in British Columbia, Canada, was linked to provincial product-level alcohol sales data. The population weighted sample included 1,217 adults aged [≥] 19 years (716 men; mean age 49.34, SD 16.98). Participants reported product-specific consumption, which was matched to retail prices to calculate individual-level PPSD. Survey weighted quasibinomial models then examined associations between PPSD and three outcomes: (1) causing harm to self or others in the past year, (2) scoring [≥] 8 on the Alcohol Use Disorder Identification Test, and (3) consuming [≥] 15 standard drinks per week. Analyses were stratified by income, education, subjective social status, and race/ethnicity. Results: Lower price per standard drink was associated with higher odds of harm (OR 3.05, 95% CI 1.25-7.40) and scoring [≥] 8 on the AUDIT (OR 2.34, 95% CI 1.37-3.99). Associations were stronger among structurally disadvantaged groups, including low-income respondents and Indigenous participants. Conclusions: Lower alcohol affordability is linked to risky alcohol use, with the strongest effects among structurally disadvantaged groups. MUP would reduce this risk and promote health equity.
Fallegger, R.; Gomez-Ochoa, S. A.; Boys, C.; Ramirez Flores, R. O.; Tanevski, J.; Pashos, E.; Feliers, D.; Piper, M.; Schaub, J. A.; Zhou, Z.; Mao, W.; Chen, X.; Sealfon, R. S. G.; Menon, R.; Nair, V.; Eddy, S.; Alakwaa, F. M.; Pyle, L.; Choi, Y. J.; Bjornstad, P.; Alpers, C. E.; Bitzer, M.; Bomback, A. S.; Caramori, M. L.; Demeke, D.; Fogo, A. B.; Herlitz, L. C.; Kiryluk, K.; Lash, J. P.; Murugan, R.; O'Toole, J. F.; Palevsky, P. M.; Parikh, C. R.; Rosas, S. E.; Rosenberg, A. Z.; Sedor, J. R.; Vazquez, M. A.; Waikar, S. S.; Wilson, F. P.; Hodgin, J. B.; Barisoni, L.; Himmelfarb, J.; Jain, S.;
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Acute kidney injury (AKI) and chronic kidney disease (CKD) are two interconnected clinical conditions, both defined by degree of functional impairment, but with heterogeneous clinical trajectories. Using new transcriptomic technologies, recent studies have described the cellular diversity in the healthy and injured kidney at the single cell level. Here, we used single nucleus transcriptomics to investigate the molecular diversity and commonalities in kidney biopsies from over 150 participants with AKI and CKD enrolled within the Kidney Precision Medicine Project (KPMP), and did so at the patient participant level. Using an unsupervised approach, we identified two multi-cellular programs associated with clinical and histopathological features of acute injury and chronic damage, respectively. We found that these programs are expressed across patients with AKI and CKD, supporting shared, rather than distinct, underlying molecular mechanisms. These programs capture tissue-level compositional changes towards adaptive and failed-repair states in tubular epithelial cells, as well as intra-cellular molecular changes characteristic of stress in all cell types. We identified subunits of the NFkB and AP-1 complexes, as well as members of the STAT family, as putative upstream regulators of the acute and chronic programs. We were able to link these continuous molecular measures of acute injury and chronic damage with urine and plasma protein profiles obtained at time of biopsy. These non-invasive protein signatures were predictive of renal outcomes in an independent cohort of 44 thousand participants from the UK biobank. In summary, unbiased identification of cellular programs in kidney disease biopsies defined molecular programs of injury cutting across conventional disease categorisation and established a non-invasive molecular link to long term patient outcomes.
Oliver, D.; Chesney, E.; Wallman, P.; Estrade, A.; Azis, M.; Provenzani, U.; Damiani, S.; Melillo, A.; Hunt, O.; Agarwala, S.; Minichino, A.; Uhlhaas, P. J.; McGuire, P.; Fusar-Poli, P.
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Background At present, there are no approved pharmacological treatments for people at clinical high risk for psychosis (CHR-P). We sought to assess the acceptability of cannabidiol (CBD): a promising candidate treatment for this population. Methods CHR-P individuals completed a survey which assessed their views on the acceptability of CBD, its expected effectiveness and side effects, and on formulation preferences. Results The sample comprised 55 CHR-P individuals (24.3 years and 69% female). Most (91%) were familiar with CBD, and had previously used cannabis (64%), and around half (42%) had tried over-the-counter CBD. 75% were willing to take CBD as an intervention for mental health problems. Most participants anticipated fewer side effects with CBD than with existing medications, and preferred tablet or capsule formulations over liquids. Discussion CBD is perceived as a highly acceptable treatment among CHR-P individuals.
Palma, F. A. G.; Cuenca, P. R.; de Oliveira, D. S.; Silva, A. M. N.; Lopez, Y. A. A.; Santiago, D. C. d. C.; das Virgens, M. N. R.; do Carmo, A. S.; dos Reis, A.; do Carmo, G. d. J.; Lima, A. M.; Almeida, R. S.; Oliva, L.; Santana, J. O.; Maciel, P.; Bourouphael, T.; Giorgi, E.; Lustosa, R.; Eyre, M. T.; Zeppelini, C. G.; Cremonese, C.; Costa, F.
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Despite the relevance of spatial mapping in analyzing the health situation and understanding the risk factors and determinants of leptospirosis, peripheral urban communities often remain invisible on maps, which tend to use data and methods that do not express community contribution nor promote local participation. Furthermore, in the implementation of sanitation interventions, the same happens: there is limited user participation, and a lack of identification of intervention needs based on the perception of community residents, failing the interventions. We conducted a cross-sectional study through collaborative mapping from February to October 2022 with 213 residents and self-declared heads-of-household in two peripheral urban communities. We analyzed the perception of sanitation needs indicated by residents and their relationship with the risk of leptospirosis in these communities. Based on community perception, sewage (NS: 87.1%; JSI/ME: 84.9%) and urban cleaning and solid waste management (NS: 25.9%; JSI/ME: 32.6%) were the sanitation needs. In NS, most participants indicated that the necessary interventions for sewage improvement were actions of sewer cleaning and sealing (26.5%), sewer cleaning and piping (23.5%), and implementation/installation/construction of a sanitary sewage network (41.4%). In JSI/ME, interventions included sewage sealing (48.7%) and piping (25.6%), in addition to actions to maintain sewage cleaning (93.3%). The removal of solid waste (trash) in the square (NS: 22.2%) and on the streets (JSI/ME: 69.2%), as well as community awareness (JSI/ME: 15.4%), were indicated as interventions to meet the needs of urban cleaning and solid waste management. Respondents agreed on where interventions should occur, which congregated around the local river. We found a negative correlation between the predicted leptospirosis seropositivity and perceived intervention needs in both study areas. The prevention of diseases such as leptospirosis in peripheral urban communities requires integrated basic sanitation interventions, encompassing different components and aligned with the local needs perceived by residents.
Veney, D. J.; Wei, L.; Miller, J. R.; Toland, A. E.; Presley, C. J.; Hampel, H.; Padamsee, T.; Bishop, M. J.; Kim, J. J.; Hovick, S. R.; Irvin, W. J.; Senter, L.; Stover, D.
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Purpose: Tumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact and durability of a concise 3-4 minute video for patient education prior to TGT in community versus academic sites and across cancer types. Patients and Methods: Patients undergoing standard-of-care TGT were enrolled at a tertiary academic institution in three cohorts: Cohort 1-breast cancer; Cohort 2-lung cancer; Cohort 3-other cancers. Cohort 4 consisted of patients with any cancer type similarly undergoing SOC TGT at one of three community cancer centers. Participants completed survey measures prior to video viewing (T1), immediately post-viewing (T2), and after return of TGT results (T3). Outcome measures included: 1) 10-question objective genomic knowledge/understanding (GKU); 2) 10-question video message-specific knowledge (VMSK); 3) 11-question Trust in Physician/Provider (TIPP); 4) perceptions regarding TGT. Results: A total of 203 participants completed all survey timepoints. Higher baseline GKU and VMSK scores were significantly associated with higher income and greater years of education. For the primary objective, there was a significant and sustained improvement in VMSK from T1:T2:T3 (Poverall p<0.0001), with no significant change in GKU (p=0.41) or TIPP (p=0.73). This trend was consistent within each cohort (all p[≤]0.0001). Results for four VMSK questions significantly improved, including impact on treatment decisions, incidental germline findings, and insurance coverage of testing. Conclusions: A concise, 3-4 minute, broadly applicable educational video administered prior to TGT significantly and sustainably improved video message-specific knowledge in diverse cancer types and in academic and community settings. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.
Syed, M. A.; Alnuaimi, A. S.; El Kaissi, D. B.; Syed, M. A.
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Background Artificial intelligence (AI) is increasingly being integrated into healthcare systems, with growing applications in clinical decision support, workflow optimization, and population health management. While substantial investments have been made in digital infrastructure, the successful adoption of AI in primary care depends critically on the readiness, awareness, and educational preparedness of healthcare professionals. Global health authorities emphasize the need for ethically grounded and workforce-focused approaches to AI integration; however, evidence on clinicians readiness for AI, particularly in primary care settings and in the Middle East region, remains limited. Objectives This study aims to assess the level of awareness, perceptions, attitudes, and educational needs related to AI among healthcare professionals working within Qatars Primary Health Care Corporation (PHCC). In addition, it seeks to examine organizational factors influencing the integration of AI-focused education in primary care and to develop an AI readiness framework that can inform targeted training strategies and policy planning. Methods This study will adopt a mixed-methods design guided by the Organizational Readiness for Change (ORC) framework, adapted for AI integration in primary care. The quantitative component will consist of an anonymous, census-style online survey distributed to all healthcare professionals across PHCC health centers and headquarters, assessing AI awareness, attitudes, training needs, and perceived infrastructure readiness. Composite AI awareness and attitude scores will be calculated, and regression analyses will be used to explore factors associated with AI readiness. The qualitative component will include semi-structured interviews and focus group discussions using maximum variation sampling to capture diverse professional perspectives. Qualitative data will be analyzed thematically, following COREQ and SRQR reporting standards. Quantitative and qualitative findings will be integrated to generate an AI readiness profile and an actionable education roadmap aligned with national digital health priorities. Discussion This study will provide the first comprehensive assessment of AI readiness among primary care healthcare professionals in Qatar. By identifying knowledge gaps, training priorities, and organizational enablers and barriers, the findings are expected to inform the development of evidence-based AI education strategies within continuing professional development frameworks. The proposed AI readiness framework may also offer a transferable model for other health systems seeking to align workforce development with responsible AI implementation in primary care.
Apostolov, A.; Pathare, A. D. S.; Lavogina, D.; Zhao, C.; Kask, K.; Blanco Rodriguez, L.; Ruiz-Duran, S.; Risal, S.; Rooda, I.; Damdimopoulou, P.; Saare, M.; Peters, M.; Koistinen, H.; Acharya, G.; Zamani Esteki, M.; Lanner, F.; Sola Leyva, A.; Salumets, A.
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The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregulated during the mid-secretory phase of the menstrual cycle. In a preclinical model of endometrial epithelial organoids, SE at physiological concentrations activates intracellular cAMP signaling, enhances epithelial metabolism, and upregulates receptivity markers without steroid hormone priming, whereas higher concentrations modestly reduce expression of a key receptivity marker PAEP/glycodelin and shift metabolism towards oxidative phosphorylation. By contrast, in stromal cells lacking detectable GLP-1R, SE disrupts decidualization, induces endoplasmic reticulum stress and suppresses cell-cycle at G2/M phase. Human embryo models, blastoids, expressed GLP-1R and underwent concordant SE-mediated transcriptional remodeling in epiblast and trophectoderm lineages, encompassing changes in metabolism and epigenetic regulation, but without shifts in lineage proportions. Notably, SE increased blastoid attachment to the endometrial epithelium in the absence of exogenous steroid hormones, suggesting enhanced epithelial-embryo interaction. Together, these findings reveal a compartment-specific mismatch, as SE augments epithelial and embryonic metabolic activity but compromises stromal support for implantation, with potential consequences for implantation due to stromal dysfunction.
Alawdat, s.; Hassan, Z. M.
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Abstract Background: Urinary tract infections (UTIs) are common health issue during pregnancy, often lead to adverse maternal and neonatal outcomes if left untreated, low knowledge contribute to high UTI rates, particularly in resource-limited settings like Jordan. To assess the knowledge levels about UTIs among pregnant women in Jordan and its association with socio-demographic characteristics. Methods: A descriptive cross-sectional study was conducted among 500 pregnant women attending antenatal clinics in four major governmental hospitals across Jordan. Data were collected using a validated questionnaire based on the Theory of Planned Behavior (TPB) comprising 25 questions, including 5 socio-demographic questions and 20 knowledge questions, scores were categorized as "adequate" or "inadequate" based on the median score. Results: Among participants, 51.4% had inadequate knowledge, while 48.6% demonstrated adequate knowledge. Higher knowledge levels were significantly associated with younger age (21-30 years), urban residence, higher education (university and postgraduate), and employment status. Conclusion: The findings highlight a knowledge gap among pregnant women regarding UTIs. Integrating targeted health education and addressing socio-demographic disparities into antenatal care, especially for women with low education and rural residence, may improve maternal outcomes. Keywords: Urinary tract infection, Knowledge, Pregnancy, Antenatal care, Jordan, Maternal health.
Zhao, Y.; Liu, F.; Chen, L.; Li, X.; Te, Z.; Wu, B.
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Background: Nursing interns are at high risk of psychological distress due to academic and clinical stressors. While poor sleep quality is linked to anxiety and depression, the buffering role of social support remains underexplored in this population. Aims: To explore the role of social support in regulating the relationship between sleep and mental health among nursing interns. Methods: A total of 396 nursing interns completed self-administered questionnaires including the Pittsburgh Sleep Quality Index (PSQI), Social Support Rate Scale (SSRS), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Hierarchical regression and simple slope analyses were used to test moderation effects. Results: Poor sleep quality was significantly associated with higher anxiety ({beta}=0.449, P<0.001) and depression ({beta}=0.535, P<0.001). Social support significantly moderated these relationships. Under low social support, the effects of sleep quality on anxiety ({beta} = 0.602) and depression ({beta} = 0.779) were stronger than under high support (anxiety: {beta} = 0.396; depression: {beta} = 0.515). Conclusions: Social support buffers the adverse psychological effects of poor sleep among nursing interns. Interventions should integrate sleep hygiene education with strategies to enhance social support.
Swinnen, M.; Gys, L.; Thalwitzer, K.; Deporte, A.; Van Gorp, C.; Vermeer, E.; Salami, F.; Weckhuysen, S.; Wolf, S. I.; Syrbe, S.; Schoonjans, A.-S.; Hallemans, A.; Stamberger, H.
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Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we included ambulatory patients aged 6 years or older with genetically confirmed STXBP1-RD. Instrumented 3D Gait Analysis (i3DGA) was performed to objectively quantify gait. Functional mobility was assessed with the Functional mobility scale (FMS) and Mobility Questionnaire 28 (MobQues28). Caregiver health-related quality of life was evaluated using the PedsQL-Family Impact Module (PedsQL-FIM). We explored associations between gait, functional mobility, STXBP1-variant type and clinical features (ID, age at seizure onset, seizure frequency, age at onset of independent walking). Correspondence between i3DGA and the Edinburgh Visual Gait Score (EVGS), an observational gait assessment, was investigated. Results Eighteen participants were included. Compared to typically developing peers, individuals with STXBP1-RD had significantly reduced walking speed, step and stride length. Gait patterns were highly variable, with the most frequent pattern being an externally rotated foot progression angle (FPA), present in 11/18 participants. At home, 93.75% of the participants (16/18) walked independently, yet community mobility was more variable: 11/16 (68.75%) walked independently, 2/16 (12.50%) with aid and 3/16 (18.75%) used a wheelchair, indicating increasing limitations with distance and environmental complexity. Earlier acquisition of independent walking strongly predicted later unassisted ambulation at community level (p<0.001). Median MobQues28 score was 57.14% and median PedsQL-FIM score was 60.42%, indicating a moderate level of mobility limitations and reduced health-related quality of life of caregivers. EVGS was highly positive correlated with i3DGA (p= 0.001). Discussion Quantitative gait analysis in individuals with STXBP1-RD demonstrates heterogenous kinematic deviations, with an externally rotated FPA emerging as the most common pattern. Age at independent walking was a clinically relevant predictor of later functional mobility. EVGS showed strong correspondence with i3DGA and may offer a more practical, semi-quantitative assessment for broader use. These findings inform clinical decision-making and guide the selection of scalable outcome measures for natural history studies and interventional trials.
McCullum, L.; Ding, Y.; Fuller, C. D.; Taylor, B. A.
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Background and Purpose: Magnetic resonance imaging (MRI) for radiation therapy treatment planning is currently being used in many anatomical sites to better visualize soft tissue landmarks, a technique known as an MRI simulation. A core component of modern MRI simulation configurations are the use of external laser positioning systems (ELPS) to help set up the patient. Though necessary for accurate and reproducible patient setup, the ELPS, if left on during imaging, may interfere negatively with image quality due to leaking electronic noise, of which MRI is sensitive to. It is currently unknown whether this leakage of electronic noise may further affect quantitative values derived from clinically employed relaxometric, diffusion, and fat fraction sequences. Therefore, in this study, we aim to characterize the impact of MRI simulation lasers on general image quality and quantitative imaging accuracy. Materials and Methods: First, a cine acquisition was used to visualize the real-time changes in image signal-to-noise ratio (SNR) from when the ELPS was deactivated to activated. To validate this effect quantitatively, the SNR was measured using the American College of Radiology (ACR) recommended protocol in a homogeneous phantom with the integrated body, 18-channel UltraFlex small, 18-channel UltraFlex large, 32-channel spine, and 16-channel shoulder coils. Next, a geometric distortion algorithm was tested in two vendor-provided phantoms while using the integrated body coil and the ACR Large Phantom protocol was tested. Finally, a series of quantitative MRI scans were performed using a CaliberMRI Model 137 Mini Hybrid phantom to validate quantitative T1, T2, and ADC while a Calimetrix PDFF-R2* phantom was used for quantitative PDFF and R2*. All scans were performed with both the ELPS both deactivated and activated. Results: Visible electronic noise artifacts were seen when using the integrated body coil when the ELPS was activated on the cine acquisition which led to a four-fold decrease in SNR using the ACR protocol. This SNR drop was not seen when using the remaining tested coils. The automatic fiducial detection algorithm was affected negatively by ELPS activation leading to misidentification when identified perfectly with the ELPS deactivated. Degradation in image intensity uniformity, percent signal ghosting, and low contrast object detectability was seen during ACR Large Phantom testing using the 20-channel Head/Neck coil. Concordance across quantitative MRI values was similar when the ELPS was both deactivated and activated while a consistent increase in standard deviation inside the ADC vials was seen when the ELPS was activated. Discussion: The extra noise induced from the activation of the ELPS during imaging should be avoided due to its potential to unnecessarily increase image noise. This is particularly true when conducting mandatory quality assurance testing for image quality and geometric distortion which utilize the integrated body coil which is most susceptible to ELPS-induced noise. Clear clinical guidelines should be implemented to make this issue known to the MRI technologists, physicists, and other relevant staff using an MRI with a supplementary ELPS for patient alignment.
Gandhi, N. R.; Fernandes Gyorfy, M.; Paradkar, M.; Jennet Mofokeng, N.; Figueiredo, M. C.; Prakash, S.; Prudhula Devalraju, K.; Hui, Q.; Willis, F.; Mave, V.; Andrade, B. B.; Moloantoa, T.; Kumar Neela, V. S.; Campbell, A.; Liu, C.; Young, A.; Cordeiro-Santos, M.; Gaikwad, S.; Karyakarte, R. P.; Rolla, V. C.; Kritski, A. L.; Collins, J. M.; Shah, N. S.; Brust, J. C. M.; Lakshmi Valluri, V.; Sarkar, S.; Sterling, T. R.; Martinson, N. A.; Gupta, A.; Sun, Y. V.
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Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of Mtb infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing Mtb-infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.
Malik, M. Z.; Mian, N. u.; Memon, Z.; Mirza, M. W.; Rana, U. F.; Alvi, M. A.; Ahmed, W.; Ummad, A.; Ali, A.; Naveed, U.; Malik, K. S.; Chaudhary, M. S.; Waheed, M.; Sattar, A.
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Background Persistent inequities in immunisation coverage, particularly among zero-dose and under-immunised children, continue to challenge Pakistan's Expanded Programme on Immunization. Weak feedback loop, inconsistent data quality, and limited real-time monitoring impede effective decision-making. This Implementation Research was conducted under the MAINSTREAM Initiative funded by Alliance for Health Policy and Systems Research (AHPSR) and supported by the Aga Khan Community Health Services Department and National Institutes of Health Pakistan to design, implement, and evaluate a digital monitoring and action planning tool to strengthen data-driven decision-making within routine immunisation systems. Methodology/Principal Findings A co-creation approach was employed to design a digital monitoring solution through inclusive consultations, key informant interviews, and focus group discussions with EPI Punjab at provincial and district levels. The solution included a customised mobile application for data collection and a Power BI visualisation dashboard to map low-coverage areas, identify drivers of dropouts and zero-dose children, and capture caregivers' information sources to inform targeted communication. The intervention was piloted in 60 households across six clusters of a Union Council of District Lahore. Advanced analytics identified reasons for non-vaccination and missed opportunities, generating tailored recommendations and practical plans for program managers. The analysis assessed acceptability, adoption, fidelity, and perceived scalability through field observations, system use, and stakeholder feedback. The co-developed digital tool enhanced visibility of coverage gaps through UC-level mapping, real-time dashboards, and structured action planning. Pilot testing in Lahore showed strong acceptability, ease of use, fidelity, and adaptability among managers, supervisors, and vaccinators. Scalability and sustainability potential were demonstrated, though barriers included leadership turnover, system fragmentation, workload pressures, and resource constraints. Conclusion The tool demonstrated feasibility to strengthen immunisation equity, accountability, and responsiveness. Co-creation with stakeholders enhanced ownership, operational relevance, and adoption, while complementing existing platforms. Sustainability will depend on effective integration, local ownership, capacity building, and accountability, while scalability requires interoperability, resource commitment, policy support, and alignment with existing workflows.
Johnson, L. R.; Bond, C. W.; Noonan, B. C.
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Background: Quadriceps weakness may reduce sagittal plane shock absorption during landing, shifting load toward the frontal plane and increasing knee abduction moment (KAM), a biomechanical risk factor for anterior cruciate ligament (ACL) injuries. Purpose: The purpose of this study was to evaluate the association between isokinetic quadriceps strength and peak KAM during drop vertical jump landing in adolescent athletes. Study Design: Secondary analysis of previously collected data. Methods: Healthy adolescent athletes completed quadriceps strength testing using an isokinetic dynamometer and a biomechanical assessment during a drop vertical jump task. Quadriceps strength was quantified as peak concentric torque and the peak external KAM was calculated during the landing phase on the dominant limb. Both strength and KAM were normalized to body mass. Linear regression was used to examine the association between normalized quadriceps strength and peak external KAM on the dominant limb. Results: The association between quadriceps strength and peak normalized KAM on the dominant limb was not statistically significant ({beta} = -0.053 (95% CI [-0.137 to 0.030]), F(1,119) = 1.62, R2 = 0.013, p = 0.206). Quadriceps strength explained only 1.3% of the variance in peak KAM, indicating a negligible association between these variables in this cohort. Discussion: Quadriceps strength was not associated with peak normalized KAM during landing, suggesting that frontal-plane knee loading during a drop vertical jump is not meaningfully explained by maximal concentric quadriceps strength alone. KAM appears to be driven more by multi-joint movement strategy and neuromuscular coordination than by the capacity of a single muscle group.
Moser, J. D.; Bond, C. W.; Noonan, B. C.
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Objectives: Compare Anterior Cruciate Ligament (ACL) Return to Sport after Injury (ACL-RSI) scores over time following ACL reconstruction (ACLR) between male and female patients aged 15 to 25 years with primary ACL injuries and ACL reinjuries. Design: Retrospective cohort design. Setting: Sports physical therapy clinics. Participants: 332 patients aged 15-25 years who underwent ACLR following either primary ACL injury or ACL reinjury, either contralateral or ipsilateral graft reinjury, and had at least one observation of the ACL-RSI. Main Outcome Measures: ACL-RSI score. Results: ACL-RSI scores significantly increased over time post- ACLR (p < .001), males reported significantly higher scores compared to females (p < .001), and patients with contralateral ACL reinjury demonstrated higher scores than those with ipsilateral ACL graft reinjury (p = .006), though there was no difference in scores between patients with primary ACL injury and ACL reinjury. A significant interaction effect of sex and injury status was also observed (p = .009), generally demonstrating that females had lower psychological readiness compared to males across injury statuses. Conclusions: ACL-RSI following ACLR varies based on biological sex and time post-ACLR, though ACL reinjury, independent of the reinjured leg, does not appear to effect scores compared to primary ACL injury.