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Gene

Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Gene's content profile, based on 41 papers previously published here. The average preprint has a 0.07% match score for this journal, so anything above that is already an above-average fit.

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A Foundational Exome Resource for Jordan: Dual Ancestry Admixture and Population-Specific Variants to Improve Clinical Variant Interpretation

Froukh, T.

2026-05-27 genetic and genomic medicine 10.64898/2026.05.23.26353895 medRxiv
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Currently, the genetic architecture of Middle Eastern populations is underrepresented in global genomic databases. This gap increases the rate of Variants of Uncertain Significance (VUSs) and clinical misinterpretations of genomic data especially in Middle Eastern populations. Whole exome sequencing was conducted on 90 healthy individuals from Jordan and the data were analysed using Principal Component Analysis (PCA) and multi-computational filtering. PCA revealed a double ancestry (EUR-AFR) admixture rather than a triple admixture (EUR-AFR-AMR). More than 3,500 populations-specific variants (PSVs) were identified, of which 72% were singletons. Additionally, 19 variants were significantly enriched compared to the maximum allele frequencies in public global databases (Fisher's exact test with Benjamini-Hochberg false discovery rate correction, p-value < 0.05). Consequently, the results suggest the reclassification of variants of Uncertain Significance (VUS) which reside in the ECE2 gene to likely benign and the variants of Conflicting Classification of Pathogenicity in the genes IL1RN and THPO to benign based on the significant allele frequency (AF=0.0389, p-value < 0.05). Furthermore, a pathogenic ClinVar variant was identified in a healthy individual, warranting careful interpretation. The findings underscore the importance of identifying PSVs in order to minimize or even prevent clinical misdiagnosis and highlight the unique genetic signature in Jordan. The study serves as a foundational resource for precision medicine in the region.

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Prevalence of nutritional, behavioral and anthropometric cancer-related risk factors among adults in Nouakchott, Mauritania: a cross-sectional study

Tolba, N.; Najdi, A.; El Hfid, M.; Hmeied Maham, M.; Brahim, S. M.; Tolba, A.; Sellal, N.

2026-05-26 epidemiology 10.64898/2026.05.23.26353924 medRxiv
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Background Cancer is a growing public health challenge in low- and middle-income countries, where urbanization, nutritional transition and lifestyle changes contribute to modifiable risk factors. In Mauritania, population-based data on cancer-related nutritional, behavioral and anthropometric risk factors remain limited. Objective To describe the frequency of the main nutritional, behavioral and anthropometric cancer-related risk factors among adults living in the three wilayas of Nouakchott. Methods A cross-sectional study was conducted among 1,000 adults aged 18 years and older in Nouakchott. Data were collected using a standardized questionnaire covering sociodemographic characteristics, dietary habits, physical activity and selected health behaviors. Anthropometric measurements were performed to assess body mass index and abdominal adiposity. Abdominal obesity was defined using sex-specific waist circumference cut-off points recommended by the World Health Organization: [&ge;] 88 cm in women and [&ge;] 102 cm in men. Results were presented as frequencies and proportions, with comparisons by sex, age group and wilaya of residence. Results Women represented 52.0% of participants, and 53.5% were aged 18-34 years. Excess body weight was frequent, with 38.6% overweight and 28.0% obese. Abdominal adiposity was also common, with 58.0% having increased or substantially increased waist circumference and 48.3% having an elevated waist-to-hip ratio. Physical inactivity was reported by 64.7% of participants, and 15.7% were current smokers. Dietary exposures included high red meat consumption in 66.8%, daily refined cereal intake in 67.5%, daily sugar-sweetened beverage consumption in 14.9%, and limited daily fresh fruit consumption in 13.8%. Significant differences were observed by sex for anthropometric indicators, by age for selected dietary habits, and by wilaya for physical activity, smoking and selected dietary behaviors. Conclusion This study shows a high frequency of modifiable cancer-related risk factors among adults in Nouakchott, particularly excess body weight, abdominal adiposity, physical inactivity and unfavorable dietary habits. These findings support the need to strengthen primary prevention strategies targeting nutrition, physical activity and tobacco control in Mauritania.

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Effects of Starting and Stopping Combined Oral Contraceptives on Markers of Ovarian Reserve

Bernig, U.; Kördel, M.; Sundström-Poromaa, I.; Kroemer, N. B.; Henes, M.

2026-06-01 sexual and reproductive health 10.64898/2026.05.29.26354411 medRxiv
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Objective To examine the effects of combined oral contraceptive (OC) use on clinical markers of ovarian reserve by comparing Anti-Muellerian Hormone (AMH), antral follicle count (AFC), and ovarian volume (OV) before and after starting or stopping OC. Methods This analysis is based on data from a prospective cohort study conducted at the University Hospital Tubingen, Germany, as part of the IRTG-2804 project. A total of 54 healthy women were included and categorized into three groups based on their OC use status: OC starters (n = 12), stoppers (n = 16), and long-term OC-users (n = 26). Each participant underwent a transvaginal ultrasound (including AFC and OV) and serum sampling (including AMH) at two time points (S1 and S2), three to six months apart. OC starters were assessed first during the early follicular phase (day 1-7) and then during active OC intake (day 8-21), while stoppers were assessed in the reverse order. Long-term users were assessed twice during active OC intake. Results OC stoppers showed significant within-group increases in all ovarian reserve markers, including AMH ({Delta} = 2.57 ng/mL, p < .001), AFC ({Delta} = 3.88, p = .004), and OV, which almost doubled (1.94-fold increase; 95% CI [1.35, 2.80], p < .001). In contrast, OC starters exhibited a significant decline in AMH ({Delta} = -1.25 ng/mL, p = .013), but no changes in AFC or OV. No significant longitudinal changes were observed among long-term OC users. Conclusion AMH levels decrease after starting OC use whereas AFC and OV are not affected. In contrast, AMH, AFC, and OV recover within three to six months after stopping OC, suggesting a reversible suppression of ovarian reserve markers during OC use. These findings are clinically relevant for fertility counseling and for the interpretation of ovarian reserve markers in women using hormonal contraception.

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Nutritional, behavioral and anthropometric factors associated with colorectal cancer in Nouakchott, Mauritania: a case-control study

Tolba, N.; Najdi, A.; El Hfid, M.; Hmeied Maham, M.; Mohamed Brahim, S.; Tolba, A.; Sellal, N.

2026-05-26 epidemiology 10.64898/2026.05.23.26353931 medRxiv
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Background Colorectal cancer is a growing public health concern in low- and middle-income countries, particularly in the context of nutritional transition and changing lifestyles. In Mauritania, evidence on factors associated with colorectal cancer remains limited. This study sought to identify nutritional, behavioral and anthropometric factors associated with colorectal cancer among adults living in Nouakchott. Methods A case-control study was conducted in Nouakchott between January and April 2026. The study included 50 confirmed colorectal cancer cases and 100 controls with no personal history of cancer. Data were collected using a standardized questionnaire covering sociodemographic characteristics, dietary habits, behavioral factors and anthropometric measurements. Crude and adjusted odds ratios with 95% confidence intervals were calculated using binary logistic regression. Results Low educational level was more frequent among cases than controls, 70.0% versus 27.0%, and remained independently associated with case status after adjustment (aOR = 4.98; 95% CI: 1.81-13.70; p = 0.002). Being married or living with a partner was also associated with case status (aOR = 3.72; 95% CI: 1.19-11.66; p = 0.024). Abdominal obesity was associated with colorectal cancer in bivariate analysis but not after adjustment. High consumption of salty foods remained associated with case status in the multivariate model (aOR = 47.45; 95% CI: 4.83-466.40; p = 0.001). However, this estimate should be interpreted with caution given the wide confidence interval and the limited sample size (n=50 cases). Refined sugars and canned foods were associated with case status only in bivariate analysis. Inverse associations observed for coffee and sugar-sweetened beverages should be interpreted cautiously because of possible reverse causality. Conclusion Low educational level and high consumption of salty foods were the most defensible factors associated with colorectal cancer in this study. These findings support strengthening nutrition-related prevention and health education interventions in Nouakchott. Larger studies with more detailed dietary assessment are needed to confirm these associations.

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Biological Age and Complication Prediction in Hypertension: A 13-Year Cohort

Kim, B.-s.; Bae, C.-y.; Kim, I.-h.; Choi, Y.-j.; Jeon, M.-h.

2026-05-29 epidemiology 10.64898/2026.05.27.26354288 medRxiv
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1. Background: With the rising prevalence of hypertension, especially among younger populations, there is a critical need to better assess health status and predict associated complications. This study developed a biological age model ("hypertension age") for hypertensive patients to predict the risk and timing of major complications. 2. Methods: Using South Korea's NHIS-NHID data, researchers analyzed 4,535,041 hypertensive patients who underwent health examinations between 2009 and 2010. Patients were followed for an average of 12.40 years (until 2022). Principal Component Analysis (PCA) was used to develop the biological age (cBA) model. The risk and onset timing of complications were analyzed using Cox proportional hazards and multiple regression models, adjusting for variables like medication use and baseline diseases. 3. Results: A 1-standard deviation (SD) increase in the age gap?where biological age exceeds chronological age (cBA - CA)?was significantly associated with an elevated risk for all major complications in both sexes (p < 0.001). Furthermore, a 1-SD increase in this gap significantly accelerated the time to complication onset for nearly all conditions (p < 0.001), with the exception of dementia in women. The impacts of medication use, hypertension duration, and baseline comorbidities varied by specific complication. 4. Conclusions: Lowering "hypertension age" relative to chronological age can significantly reduce the risk and delay the onset of major cardiovascular and related complications. Quantifying this biological age gap serves as a powerful motivational tool for personalized health management and complication prevention in hypertensive patients.

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Early Life Determinants of Forward Compression Wave Intensity in Adults

Haynes, A.; Mynard, J. P.; van der Veen, M.; Carson, J.; Green, D. J.

2026-05-27 cardiovascular medicine 10.64898/2026.05.26.26354176 medRxiv
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Intro: Characteristics of the pulse wave transmitted through the carotid arteries are predictive of cognitive decline and cerebrovascular health in humans. This study aimed to identify risk factor trajectories in childhood, adolescence and early adulthood that are associated with forward compression wave intensity (FCWI) in the common carotid artery in adults aged 28 years. Methods: Systolic blood pressure (SBP), body mass index (BMI) and fasting blood glucose (FBG) measured at multiple time-points when participants were aged between 8-20 years were included in a trajectory analysis. At age 28 years, FCWI was measured in 402 (M=206, F=196) participants who underwent a Duplex ultrasound assessment of the common carotid artery. Statistical analysis assessed differences in FCWI between each trajectory group for males and females separately. Results: In males, four trajectory groups were identified for BMI, three for SBP, and two for FBG. In females, three trajectory groups were identified for BMI, SBP, and FG. In males, having higher BMI (P=0.006), SBP (P=0.021) and FBG (P=0.002) from ages 8-20 years was associated with greater FCWI at age 28 years. In females, no associations were found between FCWI at age 28-years and trajectory groups for BMI (P=0.185), SBP (P=0.289) or FBG (P=0.070). Conclusion: Having high BMI, SBP and FBG throughout childhood, adolescence and early adulthood was associated with higher FCWI in the carotid artery at age 28 years in males, but not females. This may have a direct impact on the etiology of cognitive decline and cerebrovascular disease in later life.

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Multidomain HMOD in Ghanaian Adults: Prevalence, Predictors, and Implications

Agyapong, K. O.; Kyeremah, E.; Folson, A. A.; Agyekum, F.; Blenman, K. R. M.; Appiah, L.; Adu-Boakye, Y.; Owusu, I. K.

2026-05-30 epidemiology 10.64898/2026.05.21.26353747 medRxiv
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Background: Comprehensive assessment of hypertension-mediated organ damage (HMOD) across multiple organ systems remains limited in sub-Saharan Africa. We aimed to determine the prevalence and predictors of multidomain HMOD in a geographically diverse Ghanaian adult population. Methods: This secondary analysis of the Ghana Heart Study included 1,106 adults from four regions. Multidomain HMOD was defined as a pre-specified 9-domain TOD composite score ?2, based on the ESH/ESC 2018 guidelines framework. Logistic regression and ROC analysis were used to identify predictors and compare discriminative performance. Results: Mean age was 46.9 (17.2) years and 58% were female. Multidomain HMOD prevalence was 21.2% (235/1,106) and increased steeply with age: 8.6% (<45 years), 20.6% (45?59 years), and 44.4% (?60 years). Hypertension prevalence was 73% in the HMOD group versus 28% in those without HMOD (p < 0.001). The strongest independent associations were peripheral artery disease (OR 41.2), valvular burden (OR 14.4), and ECG-LVH (OR 9.0). baPWV showed superior discriminative performance (AUC 0.827, 95% CI 0.794?0.860) compared with the ASCVD Pooled Cohort Equations (AUC 0.466; ?AUC +0.351, DeLong test p < 0.001). Conclusions: One in five Ghanaian adults has hypertension-mediated organ damage in ?2 organ systems. baPWV is the strongest predictor and substantially improves risk stratification beyond conventional scores. These findings support the use of baPWV to guide hypertension management and HMOD assessment in West Africa.

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Associations between serum estradiol and estrone and Alzheimer's disease biomarkers: an analysis in female participants from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS)

Shin, J.; Muniz-Terrera, G.; Ritchie, C.; Manson, J.; Plachecki, S.; Kirschbaum, C.; Gregory, S.

2026-05-30 epidemiology 10.64898/2026.05.27.26354257 medRxiv
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INTRODUCTION: Postmenopausal estrogen decline may contribute to Alzheimer's disease (AD) risk, but longitudinal evidence linking circulating estrogens to cerebrospinal fluid (CSF) biomarkers is lacking. METHODS: We analyzed 866 female participants from the European Prevention of AD Longitudinal Cohort Study with baseline serum estradiol and estrone measured by liquid chromatography tandem mass spectrometry and repeated CSF measurements of amyloid-beta (A{beta})42, phosphorylated (p) Tau181, and total (t) Tau. RESULTS: Neither estradiol nor estrone was associated with longitudinal A{beta}42. Higher estradiol was associated with lower baseline tau and slower tau increases over time. Baseline estradiol-tau associations were stronger in apolipoprotein E (APOE) {epsilon}4 carriers, though APOE{epsilon}4 did not modify longitudinal associations. Amyloid positivity did not moderate hormone-tau associations but was associated with steeper tau increases over time. Estrone showed no significant associations. DISCUSSION: These findings suggest a more consistent relationship between estradiol and tau-related rather than amyloid-related pathology.

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Suspected rabies exposure among animal-bite human cases in Busia district, Uganda: Prevalence, associated factors and delayed post-exposure care-seeking. A cross-sectional study

Wagaba, D.; Nabukenya, I.; Kizza, J.; Unith, H.; Kanyange, A.; Turyahabwe, C.; Kibuuka, H.; Mugisha, D.; Ogola, S. P.; Nabidda, S.; Kisakye, L. K.; Kalyango, J.

2026-06-01 epidemiology 10.64898/2026.05.29.26354408 medRxiv
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Background Rabies is a zoonotic neglected public health problem associated with animal bites, especially domestic carnivores claiming 59,000 deaths annually predominantly in developing countries of Africa and Asia. There is a high risk of exposure among rural communities endemic with animal rabies where adoption of prevention strategies is minimal. This study determined the prevalence of suspected rabies exposure, associated factors, and delayed post-exposure care-seeking among animal-bite human cases in Busia district, Uganda. Methods: This was a cross-sectional study that involved 332 consecutively sampled animal bite human cases that occurred within the period 2023 to 2024. Data for the bite cases from records were collected using a data abstraction tool. In addition, interviewer-administered semi-structured questionnaires were used to collect data on sociodemographic, animal-related and environmental characteristics. Approximate bite locations were collected using Global Positioning System (GPS) coordinates via Kobo collect. Analysis was carried out in STATA 17 using mixed effects modified Poisson regression for factors associated with suspected rabies exposure. Results: The median age of the bite cases was 18 (IQR: 9-36) with the male gender predominantly affected. The prevalence of suspected rabies exposure was 53.6% (95% Confidence interval - CI: 46.8-60.3). Factors associated were urban versus (vs) rural residence (adjusted prevalence ratio-aPR: 1.04, 95%CI: 1.00-1.08), being bitten by a stray animal (aPR: 1.28, 95% CI: 1.22-1.35) and wild animal (aPR: 1.22, 95% CI: 1.14-1.30) vs domestic animal, vaccination status of the biting animal i.e. vaccinated vs unvaccinated (aPR: 0.76, 95% CI: 0.69-0.85), provoked vs unprovoked bites (aPR: 0.82, 95% CI: 0.79-0.86), and distance to nearest river ([&ge;]5km) vs <5km (aPR: 0.93, 95% CI: 0.87-0.99). The prevalence of delayed post-exposure seeking was 23.0% (95% CI: 16.5-31.1) among the suspected rabies exposures. Conclusion: The study reveals a high prevalence of suspected rabies exposure. Factors associated are multidimensional i.e. are of human, animal and environmental origin. The one health paradigm should be emphasized during routine surveillance of rabies-related cases. The study observed that 1 in 5 bite cases delayed to seek care post bite exposure. We recommend collaborations between sectors, routine vaccination and awareness campaigns, and monitoring of wild carnivore populations and environmental dynamics in rabies-related surveillance.

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High Incidence of Adverse Pregnancy Outcomes are Associated with Maternal Age and Infection Status in a Resource-Limited Community

Kituyi, S. N.; Odongo, A. O.; Wachuka, R.; Wambua, S.; Kobia, F.; Gitaka, J.; Kanoi, B. N.

2026-06-01 epidemiology 10.64898/2026.05.29.26354424 medRxiv
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Maternal health during pregnancy is critical for favorable birth outcomes and long-term wellbeing of both mothers and infants. Women in rural, malaria-endemic regions face unique biological and socioeconomic challenges that may increase the risk of adverse pregnancy outcomes (APOs). This study investigated the incidence and determinants of APOs among pregnant women attending antenatal care at Webuye sub-County Hospital in Western Kenya, a rural malaria-endemic setting. We conducted a retrospective cohort analysis utilizing previously collected data of 300 women enrolled during early pregnancy and followed through delivery. Maternal demographic, clinical, and infection-related factors were assessed, and associations with APOs were evaluated using chi-square tests and multivariable logistic regression. Maternal age and gestational age at enrollment were significantly associated with malaria history (P<0.001). Maternal BMI abnormality (124.5/1000 pregnancies), anemia (99.3/1000), fetal or neonatal death (81.3/1000), and preterm birth (43.8/1000) were observed (all P<0.001), suggesting a substantial burden. Younger mothers (<20 years) and older mothers (>35 years) were significantly more likely to develop anemia (P =0.026), and prior malaria infection further increased anemia risk (P =0.02). Abnormal urinalysis findings indicative of urinary tract infection were significantly associated with low birthweight (P =0.031). No significant associations were found between APOs and infant sex, parity, gravidity, or maternal ABO blood type. These findings highlight a substantial burden of APOs in this rural population, exceeding national and global estimates. Strengthening malaria prevention, nutritional support, urinary infection screening, and encouraging early antenatal care attendance are critical to improving maternal and neonatal outcomes. Targeted interventions for adolescent and older mothers, along with enhanced point-of-care diagnostics, may reduce preventable complications in similar resource-limited, malaria-endemic settings.

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Identification of a Fractional Model for an Outbreak of the Dengue Fever

Cresson, J.; Pere, M.; Szafranska, A.

2026-05-27 epidemiology 10.64898/2026.05.26.26354120 medRxiv
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This work focuses on the global and partial identification problem for fractional differential equations. We provide a general numerical procedure based on global and local optimization algorithms with two refinements for biological systems that ensure solution positivity and homogeneous parameter units. The method is applied to a new fractional model of Dengue outbreak called the Fractional Homogeneous Nishiura (FHN) model, calibrated using data of newly infected people in Cape Verde. We show that our identification method yields a better fit between data and model solutions than previous approaches and that our FHN model captures the dynamics of Dengue more closely than existing systems.

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Geospatial Analysis of Antenatal Care Utilization and Its Determinants Among Women in Ghana: Evidence from 2022 Demographic and Health Survey

Opoku, S. Y.; Weyori, E. W.; Ampon-Wireko, S.; Nawaane, P.; Asaarik, M. J. A.; Fiavor, F.; Owusua, T.

2026-05-28 sexual and reproductive health 10.64898/2026.05.27.26354191 medRxiv
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Background: Antenatal care (ANC) utilization is critical for improving maternal and neonatal health outcomes. Despite the World Health Organization recommendation of at least eight ANC contacts during pregnancy and the implementation of free maternal healthcare policies in Ghana, significant geographic and socioeconomic disparities in ANC utilization persist. This study therefore assessed the spatial distribution and geographically varying determinants of ANC utilization among women in Ghana. Methods: A cross sectional analytical study was conducted using women data from the 2022 Ghana Demographic and Health Survey. The analysis included women aged 15 to 49 years with an index child younger than five years preceding the survey. Descriptive statistics were computed using Stata version 18, while spatial analyses were conducted in QGIS version 3.44. Global Morans I was used to assess spatial autocorrelation, whereas Local Morans I and Getis Ord Gi analyses identified spatial clusters, hotspots, and coldspots of ANC utilization. Ordinary Least Squares (OLS) regression and Geographically Weighted Regression (GWR) models were fitted to assess global and local determinants of ANC utilization. Results: Overall, only 26.0% of women achieved adequate ANC utilization, while 74.0% reported inadequate ANC attendance. Adequate ANC utilization was higher among women with higher education (42.0%) and those from the richest households (41.3%) compared with women without formal education (19.1%) and those from the poorest households (17.6%). Regional disparities were observed, with Western (48.8%), Eastern (48.0%), and Greater Accra (47.3%) regions recording the highest ANC utilization, whereas Savannah (24.7%), Northern (25.8%), and North East (26.8%) regions recorded the lowest utilization levels. Global Morans I demonstrated significant positive spatial autocorrelation (Morans I = 0.457, p = 0.044), indicating geographic clustering of ANC utilization across Ghana. Getis Ord Gi analysis identified significant coldspots within Northern, Savannah, and North East regions, while Central Region demonstrated significant hotspot clustering. OLS regression showed that maternal education (B = 0.284, p = 0.003) and household wealth (B = 0.191, p = 0.011) positively influenced ANC utilization, whereas distance to health facility negatively influenced utilization (B = -0.156, p = 0.019). The GWR model demonstrated improved explanatory performance (Adjusted R-squared = 0.71), confirming substantial spatial heterogeneity in ANC determinants across Ghana. Conclusion: Adequate ANC utilization in Ghana remains low and geographically unequal. Maternal education, household wealth, and geographic accessibility significantly influence ANC utilization, with pronounced disparities concentrated within Northern Ghana. Spatially targeted maternal health interventions aimed at improving education, reducing socioeconomic inequalities, and enhancing healthcare accessibility are required to improve equitable ANC utilization across Ghana.

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Defining a person-centered conceptual model to inform measurement of contraception's effects on the menstrual cycle

Mackenzie, A.; Smit, J.; Miric, M.; Edelman, A.; Beksinska, M.; Catano, A.; Chung, S.; Cuevas, E.; Delacerda, M.; Forbes, M.; Hoppes, E.; Ingeno, L.; Jacobson, L.; Khomo, M.; Lebetkin, E.; Majola, T.; Matos, M.; Mavundla, M.; McCaffrey, S.; Mendez, A.; Mendez, M.; Mhlaba, N.; Mosery, N.; Ndlovu, L.; Qiya, B.; Stankevitz, K.; Sullivan, A.; Zulu, B.

2026-05-30 sexual and reproductive health 10.64898/2026.05.21.26353514 medRxiv
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Objective: To address the need for improved measurement of the ways contraception impacts the baseline menstrual cycle (i.e., contraceptive-induced menstrual changes; CIMCs) by assembling an interdisciplinary, global research collective to rigorously develop a person-centered measure for CIMCs in multiple languages. As the first step, this paper reports on our conceptual model development, which is the foundation for ongoing measure development. Study design: We conducted 18 focus groups with 106 people experiencing CIMCs while using hormonal or intrauterine contraception in Durban, South Africa, Santo Domingo, Dominican Republic, and Portland Oregon, United States. We used a virtual affinity mapping approach to analyze qualitative data, which was the basis of our conceptual model along with relevant theory and related models in the literature. Results: The conceptual model of experiences with CIMCs depicts the baseline menstrual cycle, including CIMCs and conceptually-linked effects and the impacts and perceptions of those CIMCs. We found key domains of changes in pain, bleeding volume, bleeding patterns, and characteristics of blood. Conclusion: Our CIMC conceptual model will inform development of a measure with evidence of validation across three language and global contexts. Adoption of a person-centered, standardized CIMC measurement across trials will improve knowledge and decision-making between methods.

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DKK1 and CKAP4 expression is associated with cervical lymph node metastasis in tongue squamous cell carcinoma

Fujita, H.; Takahashi, O.; Yada, N.; Tanaka, J.; Haraguchi, K.; Morioka, M.; Yaginuma, T.; Sasaguri, M.; Kokabu, S.; Habu, M.

2026-06-01 dentistry and oral medicine 10.64898/2026.05.29.26354440 medRxiv
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Objective: To identify Dickkopf-1 (DKK1) as a prognostically relevant candidate in head and neck squamous cell carcinoma and to evaluate whether DKK1 and cytoskeleton-associated protein 4 (CKAP4) expression is associated with cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC). Methods: DKK1 was screened using the Human Protein Atlas Pathology Atlas. Immunohistochemical expression of DKK1 and CKAP4 was examined in 54 patients with primary TSCC (cT1-4N0) treated surgically between 2015 and 2020. Nine cases were excluded because of insufficient tissue blocks or inadequate staining quality, leaving 45 evaluable cases. Associations with delayed cervical lymph node metastasis were assessed together with conventional clinicopathological factors, including infiltrative growth pattern (INF) and pathological depth of invasion (pDOI). Results: In public database analysis, high DKK1 expression was associated with poorer overall survival in head and neck squamous cell carcinoma. In the TSCC cohort, pDOI [&ge;]5 mm and INF pattern c were significantly associated with cervical lymph node metastasis. Positive DKK1 and CKAP4 expression were also significantly associated with cervical lymph node metastasis. Furthermore, combined DKK1/CKAP4 positivity, when incorporated with INF and pDOI, provided additional risk stratification, and cases with all 3 factors showed a markedly increased likelihood of cervical lymph node metastasis. Conclusions: Expression of DKK1 and CKAP4 was associated with cervical lymph node metastasis in TSCC. Combined assessment of DKK1/CKAP4 expression with INF and pDOI may improve pathological risk stratification and may help identify patients who require closer neck evaluation and postoperative management.

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Wilson's Central Terminal Changes Location on the Body Surface During the P-Wave: Why Precordial Leads Might Not Be What We Think

Bender, J.; Stoks, J.; Barrios Espinosa, C.; Becker, S.; Cluitmans, M. J. M.; Loewe, A.

2026-05-28 cardiovascular medicine 10.64898/2026.05.20.26352966 medRxiv
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Background and Aims: Clinical interpretation of the precordial leads V1-V6 assumes that Wilson's central terminal (WCT) has a fixed anatomical location. Consequently, a positive signal corresponds to electrical activation spreading from WCT towards the respective electrode, and vice versa. However, the location of WCT has never been systematically investigated. Yet, a better understanding of WCT location could improve the interpretation of the precordial leads. This work aims to characterize the spatial expansion and location of the physical WCT i.e., the electrical potential defined by the WCT, during the P-wave on the body surface. Methods: An intensive analysis of body surface potential maps (BSPMs) during atrial depolarization in an in silico patient cohort and clinical data was conducted. Results: During the P-wave, the location of WCT was not stationary but the spatial extent and location varied across time as well as across individuals. Four distinct spatial patterns of WCT distribution on the body surface were identified in silico, and three of these were found in the clinical cohort. WCT signals agreed with BSPM signals at commonly assumed positions of WCT only for a small fraction of the P-wave. Conclusion: The spatial extension and location of WCT changes during the P-wave and thus should be considered when interpreting the precordial leads.

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Impact of AI-Assisted Mammography Reading on Quality Indicators in the Czech Breast Cancer Screening Programme: A Retrospective Study

Veverkova, L.; Dolezalova, Z.; Marackova, V.; Mathew, E.; Urbankova, M.; Ambrozova, M.; Piskovsky, T.; Ngo, O.; Majek, O.

2026-05-26 oncology 10.64898/2026.05.25.26353869 medRxiv
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Objectives: The aim of mammographic screening is the early detection of invasive cancers. In the era of artificial intelligence (AI), this tool may improve diagnosis of earlier stages. The purpose of this study was to assess the impact on selected quality indicators retrospectively. Method: The data source was the Breast Cancer Screening Registry using data from one Screening Unit that currently uses AI routinely. The indicators of the cancer detection rate (CDR), further assessment rate (FAR), and recall rate (RR) in the year 2023, when AI was used, and the year 2022, without AI, in women aged 45-69 were compared. The statistical evaluation used the chi-square test and logistic regression adjusting for the effects of age, a woman's risk level, and the screening round at a 5% significance level. Results: In 2022, without AI, 4,034 women aged 45-69 were included, compared with 4,049 women in 2023 when AI was used. This study showed a non-significant increase in CDR from 5.0 breast cancers detected per 1,000 women (non-AI assessment) to 5.2 (AI-assisted assessment), p = 0.919; OR (95% CI): 1.034 (0.542-1.974), a significant decrease in the FAR from 5.2% to 3.9%, p < 0.001; OR (95% CI): 0.665 (0.529-0.836), and a decrease in RR from 2.4% to 1.9%, p = 0.083; OR (95% CI): 0.754 (0.548-1.037). Conclusion: AI has the potential to be a useful tool in the early detection of breast cancer by improving quality through a decrease in FAR and RR, while probably maintaining CDR.

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Health Literacy and Lifestyle Scores Among A Small but Diverse Group of Older Asian Adults Who Attended Community Health Events in Los Angeles

Zhang, E.; Tran, T.; Shun, K.; Tran, D.; Tsai, A.; Kwang, E.; DerSarkissian, M.; Kuo, T.

2026-05-29 epidemiology 10.64898/2026.05.27.26354181 medRxiv
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The Asian population in Los Angeles is among the largest and most heterogeneous in the U.S. This is true culturally and health-wise. Older Asians have differing risks for cardiovascular and cardiometabolic disease, depending on their ethnicity, health literacy, and lifestyle choices. This pilot examines several of these factors in a small but diverse group of older Asian adults who attended community health events from 2024-2025. Self-reported and biometric data were collected at five such events hosted by the Asian Pacific Health Corps at UCLA. The pilot generated health literacy and lifestyle (HLL) scores for all participating attendees and explored how they relate to their socio-demographics, healthcare habits, and predictions of their own health data. Overall, there were significantly more females than males with higher HLL scores (p = 0.027). College education (p = 0.028) and "normal" ranges for biometric data (e.g., blood pressure, BMI, blood glucose, cholesterol) were related to higher median HLL scores. With a few exceptions, fewer than 50% accurately predicted their biometric numbers regardless of HLL scores, suggesting a disconnect between perception and reality, and that better provider-patient communication may help foster greater patient understanding about their chronic conditions. These HLL score distributions indicate that educational attainment, better awareness of one's health, and high health literacy are individual factors that may influence older Asians' understanding and potential approach to managing their health conditions.

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Dengue spatiotemporal patterns in Minas Gerais, Brazil, 2014-2023: regional epidemic forces dominate over the environmental impact of the Brumadinho dam collapse

Fernandes, G. d. R.; Vaz, A. B. M.; Fonseca, P. L. C.; Oliveira, W. K.; Aguiar, E. R. G. R.; Lopes, B. C.; Mota-Filho, C. R.; Castro, M. L. P.; Starling, C. E.

2026-05-26 epidemiology 10.64898/2026.05.19.26353615 medRxiv
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Background: Dengue is a major public health problem in Brazil, and Minas Gerais is one of the states with the highest burden. In January 2019, the Brumadinho dam collapse released about 12 million cubic meters of iron ore tailings into the Paraopeba River basin, causing environmental disturbance that could plausibly affect vector habitats and dengue transmission. We evaluated the spatiotemporal dynamics of dengue in Minas Gerais from 2014 to 2023 and tested whether the disaster was associated with changes in affected municipalities. Methods: We performed an ecological spatiotemporal analysis using dengue notifications from SINAN for all municipalities in Minas Gerais (2014-2023). Municipalities were classified as Paraopeba basin, regional controls, or state controls. Temporal similarity was assessed using Pearson correlation-based hierarchical clustering and non-metric multidimensional scaling (NMDS). Sources of variation were examined with PERMANOVA and principal component analysis (PCA). A linear mixed-effects model with municipality as a random effect was used to test changes after 2019, with pre/post contrasts estimated from marginal means. Results: Dengue showed strong temporal synchrony across the state, with major epidemic peaks in 2015-2016, 2019, and 2023. Health region explained 31.5% of the variation in temporal incidence profiles (p = 0.001), whereas Paraopeba basin status explained no significant variation (p = 0.998). No temporal cluster was enriched for municipalities in the Paraopeba basin. PCA identified 2023, 2019, and 2016 as the main years driving variability. In the mixed model, year was significant (p < 0.001), but Paraopeba basin status and its interaction with time were not. Incidence increased significantly after 2019 in non-exposed municipalities (p < 0.001), but not in basin municipalities (p = 0.088). Conclusions: Dengue dynamics in Minas Gerais were driven mainly by regional and state-wide epidemic processes, with no significant independent effect of the Brumadinho dam collapse on notified dengue patterns.

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Prevalence and Characteristics of Steatotic Liver Disease in Germany - Magnetic Resonance Imaging in the German National Cohort (NAKO)

von Itter, M.-N.; Grune, E.; Nonnenmacher, T.; Rach, S.; Flis, M.; Haueise, T.; Weiss, J.; Brenner, H.; Keil, T.; Roden, M.; Schulze, M. B.; Schulz-Menger, J. E.; Völzke, H.; Stefan, N.; Schlett, C. L.; Kauczor, H.-U.; Machann, J.; Bamberg, F.; Nattenmüller, J.; Norajitra, T.; Rospleszcz, S.

2026-06-01 endocrinology 10.64898/2026.05.29.26354407 medRxiv
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Background and Aims: Steatotic liver disease (SLD) has high clinical and public health relevance. Robust population estimates of SLD and its subcategories are challenging due to the limitations of ultrasound measurements or non-invasive scores, particularly for low-grade steatosis. We aimed to quantify SLD prevalence using magnetic resonance imaging (MRI) in the population-based German National Cohort (NAKO). Methods: Hepatic multi-echo Dixon MRI was performed at 5 dedicated study sites with identical setup across Germany. Liver fat (proton density fat fraction, PDFF), R2* as proxy for liver iron, and liver volume were assessed. The resulting data of N = 29'842 individuals (age range 20-72 years) were weighted by survey weights for regional representativeness, resulting in a sample of 50% women and a mean age of 45.6 years. SLD was defined as PDFF [&ge;] 5.75%, and sex-specific prevalence according to age, BMI, socioeconomic status and geographic region was calculated. Results: Overall, SLD prevalence was 21.3% in women and 35.7% in men, and the majority were metabolic dysfunction-associated (MASLD, 89.3% of all SLD cases). Prevalence increased with age in a sex-specific pattern, suggesting potential menopausal effects in women. There was a relevant prevalence of SLD in individuals with normal weight (5.3% in women, 13.2% in men) and the age group <25 years (7.5% in women, 11.9% in women). Differences in prevalence between low and high socioeconomic status were more pronounced in women (37% vs 15.8%) compared to men (45.5% vs 30.3%). Conclusions: Data underscore the high public health relevance of SLD and its subcategory MASLD. The considerable prevalence in groups historically considered low-risk, such as younger or lean individuals, emphasizes the need for raising awareness early.

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TROMBIX-DZ: A real-world, prospective, observational study of Algerian patients with atrial fibrillation treated with rivaroxaban

Moulay Brahim, A. S.; Lekkam, S.; Helal, S.; Aouchar, M.; Benbitour, I.; Noual, L.; Aoudia, Y.; Adjeroud, N.; Ait Messaoudene, M. S.; Afif, M.; Lahmer, H. M. A.; Eid, H.; Laredj, N.; Aouiche, B.; Hamdi, R.; Beddai, M. F.; Berboucha, S.; Boudjelal, T.; Boumaaza, S.; Fernane, T.; Kachenoura, A.; Kaiter, Z.; Nemmar, N.; Lassakeur, N.; Mouffok, M.; Nassour, N.; Sebbagh, G.; Okbi, R.

2026-05-27 cardiovascular medicine 10.64898/2026.05.26.26353979 medRxiv
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Background: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide, representing the primary cardiac etiology of stroke. In recent years, direct oral anticoagulants (DOACs) have shown favorable results in terms of efficacy and safety in the prevention of thromboembolism in patients with AF. TROMBIX-DZ study investigated the safety and efficacy of rivaroxaban in routine clinical settings in response to the need for real-world evidence on the use of DOACs. Methods: We carried a national, multicenter, prospective, observational cohort study to evaluate the safety and efficacy of rivaroxaban in Algerian patients with atrial fibrillation. Patients were followed-up at 3 months intervals for 1 year. The primary outcome of this study was to evaluate the safety of rivaroxaban, reported as the frequency of treatment-emergent serious adverse events (SAEs); Secondary outcomes assessed the frequency of thromboembolic events, adverse events (AEs), and treatment persistence. Results: TROMBIX-DZ enrolled 398 eligible patients with AF from 19 specialized public and private cardiology centers across different regions in Algeria. The mean age was 70.5 {+/-} 11.94. 71.9% of patients received once daily rivaroxaban 20mg, and 28.1% received the 15mg dose. The most common comorbidities included, hypertension (77.1%), diabetes (28.6%) and heart failure (25.4%), prior strokes and TIA (8.8%), and prior major bleeding (3.1%). The mean CHA2DS2-VASc score was 3.147 {+/-} 1.3, and the mean HAS-BLED score was 1.682 {+/-} 1.198; 14.06% of patients had Creatinine clearance < 50 ml/min. A total of 5.77% had treatment-emergent AE, and 1.76% had treatment-emergent SAE. The incidence rate (events per 100 patient-years) of treatment-emergent major bleeding events, treatment-emergent thromboembolic events and all-cause death during the study period were 2.1, 0.9, and 4.18, respectively. Treatment persistence was 75.88% at the end of the study. Conclusion: TROMBIX-DZ study, the first cohort in the Maghreb region, provides important insights into the safety and efficacy of rivaroxaban in Algerian population with atrial fibrillation receiving standard medical care. Rates of major bleeding and stroke were low and broadly consistent with previous international real-world registries. Trial registration number: Clinicaltrial.gov: (NCT06184204). Keywords: Direct oral anticoagulants, Rivaroxaban, Atrial fibrillation, Major bleeding, Stroke, Thromboembolism, The Maghreb region, Real-world.