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Acta Tropica

○ Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Acta Tropica's content profile, based on 13 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Factors Associated with Divergent Introgression Outcomes from Wolbachia-Based Interventions in Rio de Janeiro, Brazil

Nelson, E.; Carcamo, P. M.; Ribeiro dos Santos, G.; Sylvestre Ribeiro, G.; Rodrigues da Costa, T.; Ilaria Dorigatti, I.; Salje, H.; Moreira, L. A.; Cummings, D. A. T.; Ko, A. I.

2026-10-21 infectious diseases 10.64898/2026.10.16.26365711 medRxiv
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Wolbachia-based interventions were less effective in achieving introgression in Rio de Janeiro than other settings. Reduced introgression occurred in locations where dengue was historically high, raising concerns of inequity. We examined factors affecting Wolbachia introgression in Rio through trajectory modeling, spatiotemporal Bayesian models, and Ae. aegypti abundance estimation. During the intervention (2017-2020), Wolbachia introgression was 26% (median; IQR,14-44%), with four distinct trajectories. Despite receiving more releases, densely populated areas with low socioeconomic status had lower introgression. In spatiotemporally explicit multivariable regressions, higher Ae. aegypti abundance, temperature, population density and lower socioeconomic status were associated with reduced introgression. Improved characterization of Ae. aegypti abundance and other structural/environmental predictors of introgression could be used to calibrate release doses to ensure equitable benefits from Wolbachia interventions.

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Compound climate extremes predict dengue risk at operational lead times across Brazil

Fletcher, C.; Mila, C.; Moirano, G.; Araujo, E.; Lührsen, D.; Codeco, C.; Codeco Coelho, F.; Lowe, R.

2026-10-19 public and global health 10.64898/2026.10.16.26365716 medRxiv
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Brazil has one of the highest dengue burdens globally, with transmission influenced by climate events. Yet, the effects of compound climate extremes on dengue risk and prediction have not been quantified to date. Using a Bayesian spatiotemporal model of monthly dengue cases across 435 health regions from 2010 to 2025, we estimated relative risk associated with interacting long-lag and short-lag drought indicators and temperature anomalies across nine Koppen-Geiger climatic zones, adjusting for absolute temperature and El Nino-Southern Oscillation. Long-lag dry, mid-lag warm and short-lag wet conditions were associated with the highest relative risk in five climatic zones, with temperature anomalies modifying hydrometeorological dynamics more strongly in temperate than tropical areas. Climate covariates improved the prediction of case counts and outbreaks compared to baseline models at lead times of 1, 3, 6 and 12 months, and for the upcoming season 5 months ahead. Improvements were greatest in the Northeast, Southeast, and Midwest. Recent dengue incidence provided the greatest improvement at the 1-month lead, whereas combining incidence with climate information performed best at 3- and 6-month leads. We extended our framework to weekly state-level predictions of the season ahead to align with national public health planning. We proposed a multi-staged dengue forecasting approach to enhance early warning and response across Brazil.

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Plasma proteomic profiling identifies country-specific diversity in visceral leishmaniasis patients across East Africa

Cunha, J.; Addisu, A.; Matano, D.; Younis, B.; Bayiyana, A.; Kumar, R.; Tiwari, R.; Engel, J.; Hogg, K.; Wiggins, R.; Biwott, W.; Osuna, F.; Ichugu, C.; Zeleke, A. J.; Ayele, E.; Sande, O. J.; Khalil, E. A. G.; Ibrahim, H. M. H.; Mahmoud, M. A.; Zakaria, A. I. B.; Adiko, B.; The Immstat@Cure Consortium, ; O'Toole, P.; D'Alessio, F.; Lacey, C. J. N.; Engwerda, C. R.; Sundar, S.; Mbui, J.; Hailu, A.; Mbuchi, M.; Musa, A.; Olobo, J.; Kaye, P. M.

2026-10-21 infectious diseases 10.64898/2026.10.16.26365713 medRxiv
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Background: Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by parasites from the Leishmania donovani complex. VL is endemic in 54 countries, with East Africa (EA) accounting for [~]70% of the global burden. Therefore, there is a pressing need to prioritize VL research in EA. Transcriptomics analysis in rodent models and patients following treatment have shown that immune homeostasis is not restored by the end of treatment. However, comprehensive proteomic studies in VL remain scarce, and the few available studies were conducted outside EA. Methodology/Principal Findings: As a part of ImmStat@cure consortium, we used the Olink Reveal proximity extension assay to profile circulating proteins in VL patients from Ethiopia, Kenya and Sudan. By comparing patients at admission and 17 days after treatment with SSG-PM, we have identified a systemic Th1-cytotoxic inflammatory profile at admission, characterized by high abundance of IFN{gamma}, IL-1B, IL-6, and the granzymes A and B. Chemokines with high abundance included CXCL8/10/11, CCL3, CCL4, CCL8, CXCL8 and CCL20, consistent with the recruitment of monocytes, macrophages, T cells, and NK cells. There were also evidence of immune regulation/exhaustion, with high levels of PD1, PD-L2, IDO1 and KYNU. Although the immune profiles were similar at admission, country specific differences were observed after treatment. Kenyan patients exhibited a sustained inflammatory profile and signatures of myeloid recruitment, characterized by high levels of IL-1B, IL-6 , IL-12A, CXCL8, CCL2, CCL3, CCL4, CCL7 and CEBPB. Sudanese patients showed signatures associated with lymphocyte activation and immune regulation. Conclusions/Significance: These results highlight the complexity of the immune changes associated with VL, identifying both core conserved profiles at admission and country-specific profiles after treatment. The data provided here will provide a valuable resource for future comparative studies across more diverse different geographic regions, for linkage studies that assess the impact of parasite genotype on immune / metabolic response and for use during the evaluation of new therapies against VL.

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Mapping county-level tick-borne disease risk in Illinois by integrating vector abundance, pathogen prevalence, and phenology

Hussain, A.; Bhowmick, S.; Mateus-Pinilla, N.; Smith, R. L.

2026-10-16 epidemiology 10.64898/2026.10.14.26365569 medRxiv
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Tick-borne disease risk reflects the combined influence of vector abundance, pathogen prevalence, human exposure, and seasonal activity, yet these components are rarely integrated at the county level. We developed species-specific ecological risk scores for three medically important tick species (Acari: Ixodidae): Amblyomma americanum (L.), Dermacentor variabilis (Say), and Ixodes scapularis Say, across all 102 Illinois counties using data from 2019 to 2022. County-level predicted tick abundance and pathogen prevalence were scaled and combined using equal weights to generate primary vector-level risk scores. Robustness to the equal-weight assumption was evaluated by systematically varying the relative weights assigned to abundance and pathogen prevalence, while a separate sensitivity analysis incorporated reported tick-bite incidence where available. Associations with human disease were evaluated using negative binomial regression of tick-borne disease case counts on the corresponding risk scores, with county population included as an offset. Monthly phenology indicators were constructed by integrating human disease cases, reported tick bites, and sampled tick abundance and were evaluated in relation to temperature and precipitation. Seasonal risk was estimated by combining county-level vector risk with species-specific monthly phenology, generating monthly risk surfaces that were deployed through an interactive R Shiny application. Higher risk scores were significantly associated with greater disease case rates for each tick species. County rankings were highly stable under moderate changes in abundance and prevalence weighting. Seasonal activity differed among species, with A. americanum and D. variabilis showing concentrated warm-season risk and I. scapularis exhibiting a broader seasonal profile. These county-level seasonal risk maps identify where and when relative tick-borne disease risk is elevated in Illinois, supporting targeted prevention, surveillance, and clinical awareness.

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Impact of anemia on length of hospital stay among patients hospitalized for severe malaria in Brazzaville, Republic of the Congo

Ekat, M. H.; Amona, M.; Andzi Barre, M.; Bendett Lebaho, P.; Aloumba, G. A.; Adoua Doukaga, T.

2026-10-16 infectious diseases 10.64898/2026.10.14.26365597 medRxiv
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Background: Severe malaria remains a major cause of hospitalization in malaria-endemic sub-Saharan Africa, and anemia is among its most frequent severity criteria. Data on the impact of anemia on hospital length of stay (LOS) among adults with severe malaria remain limited in Central Africa. We assessed the impact of anemia on LOS among adults hospitalized for severe malaria in Brazzaville, Republic of Congo. Methods: We conducted a cross-sectional, descriptive, and analytic study of medical records from adult patients ([&ge;]18 years) diagnosed with severe malaria (WHO criteria) and admitted to four hospitals in Brazzaville between January 2020 and December 2024. We dichotomized LOS as short (<5 days) or prolonged ([&ge;]5 days). Multivariable logistic regression, using a backward stepwise procedure, identified factors independently associated with prolonged LOS; isolated hemoglobinuria served as the reference severity category. Results: Among 523 patients hospitalized for severe malaria, 296 met the inclusion criteria. Median age was 25.5 years (IQR 20-40); 51.7% were female, and 82.1% had a low socioeconomic status. Median hemoglobin was 10.55 g/dL, and median LOS was 4 days (IQR 3-5). In multivariable analysis, prolonged LOS was independently associated with delay to consultation (aOR 1.25/day, 95% CI 1.09-1.44), isolated anemia (aOR 7.07, 1.23-40.55), convulsions (aOR 5.86, 1.81-18.97), prostration (aOR 4.42, 1.21-16.2), and impaired consciousness (aOR 4.29, 1.17-15.7). The strongest associations involved combined severity criteria: anemia with prostration (aOR 8.58), anemia with jaundice or hemoglobinuria (aOR 16.21), and impaired consciousness with anemia (aOR 33.31). Conclusions: Anemia is a major, potentially modifiable determinant of prolonged hospitalization in adults with severe malaria, with a markedly amplified effect when combined with neurologic impairment. Early anemia screening, improved access to safe blood transfusion, and reduced delays to care could shorten hospital stays and ease the burden on health systems in this setting.

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Expanding Kelch13 artemisinin resistance markers are associated with higher malaria incidence in Uganda

van Wyk, S.; Gwasupika, J.; Mapahla, L.; Asua, V.; Harrison, L. E.; Kamya, M. R.; Nankabirwa, J. I.; Barnes, K. I.

2026-10-20 infectious diseases 10.64898/2026.10.19.26365887 medRxiv
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Artemisinin partial resistance (ART R) associated Plasmodium falciparum Kelch13 mutations is expanding across Africa. However, their population level consequences remain poorly understood, particularly in settings of moderate to high malaria transmission. We investigated associations between Kelch13 and partner drug mutation prevalence and monthly confirmed malaria incidence across 16 Ugandan districts from 2017 to 2022, using integrated molecular, epidemiological, climatic, malaria control, and antimalarial resistance data and negative binomial regression. Combined prevalence of WHO validated and candidate Kelch13 mutations increased over the study period. Each 10 percentage point increase in Kelch13 prevalence was associated with a 13.1% higher incidence after multivariable adjustment (aIRR 1.131, 95% CI 1.090 to 1.174). Furthermore, each 10% increase in pfcrt K76T was associated with a 24% increase in malaria transmission. As expected, ITN distribution >80%, IRS coverage >90%, and higher altitude were associated with lower incidence, whereas temperatures of 25 to 30C, relative humidity of 60 to 80%, and higher precipitation were associated with higher incidence. The persistence of the Kelch13 and pfcrt K76T association after adjustment suggests that expanding ART R associated parasite populations are independently associated with malaria incidence. The relationship may be bidirectional. These findings support interpreting ART R within its ecological and intervention context and integrating molecular, epidemiological, and malaria control surveillance to safeguard antimalarial efficacy.

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Quantifying Fine-scale Vegetation Associated with Ixodes scapularis Density to Inform Public Health Programming, Western Massachusetts

Tsalah, J. M.; Bobskill, V.; Ravenhurst, J.; Ross, K.; Gardner, A.; Landesman, W.; Lover, A. A.

2026-10-20 epidemiology 10.64898/2026.10.14.26363243 medRxiv
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Vegetation plays a critical role in shaping fine-scale tick density by structuring local microclimates, habitat resources, and host interactions that largely determine tick survival and activity, with implications for tick-borne disease transmission. Tick burden in the United States continues to increase, with annual reported tick-borne disease cases more than doubling from 2004 through 2019. These trends call for a broader scope of tick-mitigation strategies that go beyond traditional prevention measures that focus on personal protection; and there is an opportunity to inform habitat-level interventions. Here, we quantify fine-scale vegetation structure across 48 subplots at tick surveillance sites in Western Massachusetts to assess local habitat features associated with Ixodes scapularis density and potential for human-tick contact risk. In assessing understory and overstory vegetation attributes, this study identified life stage-specific differences in predicted tick density, with higher adult densities in areas with deeper leaf litter and presence of invasive plant species and nymphs associated with high presence of ferns. Both adult and nymphal Ix. scapularis were predicted at higher densities in relatively low basal area forests (18.9 to 26.9 m2/hectare). This study design provides a simple, low-cost framework for organizations looking to incorporate tick-informed forest measurement ecology into their public health tick surveillance protocols with minimal training.

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Assessing Knowledge and Risk Perception of Mosquitoes and Mosquito-Borne Viruses Among Medical Students in Cyprus: A Cross-Sectional MosquitoWise Study

Dali, A. M.; Vujicic, A.; Gato, D.; Volkan, E.

2026-10-19 medical education 10.64898/2026.10.15.26365696 medRxiv
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Abstract Background: Cyprus has transitioned into a high-alert zone for mosquito-borne viruses. This necessitates a proactive assessment of its future physicians. Following the 2022 re-establishment of Aedes aegypti in Larnaca and Aedes albopictus in Limassol, Cyprus, the island is now biologically primed for local outbreaks of dengue, Zika, and chikungunya, alongside Culex-borne West Nile virus. The study assessed medical students' knowledge and risk perception. Methods: A cross-sectional online survey administered the validated MosquitoWise Health Belief Model instrument to undergraduate-entry and graduate-entry students at a university in Cyprus in mid-2026. Results: Of 1023 students, 119 responded (11.6%), with pre-clinical students overrepresented (p<0.001). Mean knowledge was 5.43/9, stronger on mosquito biology (72.5%) than virus knowledge (54.2%). Median severity was 6.00/7 against susceptibility 4.25/7. Knowledge differed by study stage (p<0.001), correlated with severity (rs = 0.399) but not susceptibility. Conclusions: The study establishes a critical baseline for pre-clinical medical students in Cyprus. Overall, participants performed better on mosquito biology when compared to mosquito-borne viruses and how they spread. Our findings highlight the value of integrating theoretical microbiology with clinical practice in medical education to enhance physicians' preparedness for the changing landscape of newly emerging infections in Cyprus and across Europe as a whole. Key Words: Arboviruses, Cross-Sectional Studies, Cyprus, Health Belief Model, Medical Students, Risk Perception.

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Roles, Challenges, and Solutions for Maternal and Child Health in rural Communities in Bangladesh

Abdullah, A. S.; Halim, A.; Haq, F.; Sayem, A. S. M.; Dalal, K.

2026-10-21 public and global health 10.64898/2026.10.18.26365859 medRxiv
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Background Despite substantial improvements in maternal and child health over the past two decades, preventable maternal and neonatal morbidity and mortality remain major public health concerns in rural Bangladesh. Community-based interventions involving Community Volunteers (CVs), Community Groups (CGs), and Community Support Groups (CSGs) have been introduced to strengthen maternal and child health (MCH) services through health promotion, community engagement, and improved linkage with primary healthcare facilities. This study explored the roles, challenges, and opportunities of these community-based platforms in improving maternal and child health services. Methods A qualitative study was conducted in Kalaroa Upazila of Satkhira District, Bangladesh, between July and October 2020. Data were collected through focus group discussions and in-depth interviews with mothers, Community Volunteers, Community Group members, and Community Support Group members. Participants were purposively selected to capture diverse experiences from intervention and comparison areas. Interviews were conducted using semi-structured guides, audio-recorded with informed consent, transcribed verbatim, translated into English, and analyzed thematically using an inductive approach. Results Participants from intervention areas demonstrated greater knowledge of birth preparedness, antenatal care, pregnancy danger signs, institutional delivery, postnatal care, and newborn care than those from comparison areas. Community Volunteers, CGs, and CSGs played important roles in identifying pregnant women, conducting household counselling, promoting skilled maternal healthcare, facilitating referrals, and strengthening community participation. Participants perceived that these activities increased maternal awareness, improved health-seeking behaviour, and enhanced utilization of maternal and newborn health services. However, persistent barriers, including socio-cultural beliefs, financial constraints, transportation difficulties, shortages of skilled healthcare providers, and inadequate logistical support for community volunteers, continued to limit equitable access to quality services. Participants recommended strengthening community awareness programmes, improving community clinic readiness, enhancing referral systems, and providing regular training and supportive supervision for community-based health workers. Conclusions Community-based maternal health interventions involving Community Volunteers, Community Groups, and Community Support Groups contribute to improved maternal knowledge, health-seeking behaviour, and utilization of essential maternal and newborn health services in rural Bangladesh. Sustaining these gains will require stronger primary healthcare services, continued community engagement, and targeted strategies to address persistent health system and socio-cultural barriers. These findings provide important evidence for strengthening community-based maternal and child health programmes in Bangladesh and similar resource-constrained settings.

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A nanopore-based amplicon-sequencing panel to determine the origin and zoonotic host species of Plasmodium knowlesi infections

da Silva, G.; Tapaopong, P.; Holzschuh, A.; Sattabongkot, J.; Nguitragool, W.; Koepfli, C.

2026-10-19 infectious diseases 10.64898/2026.10.16.26365752 medRxiv
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Population genomic studies have revealed strong regional structure in Plasmodium knowlesi across Southeast Asia. To facilitate routine genomic surveillance, we developed a targeted amplicon sequencing panel that preserves the large- and small-scale population genetic structure. We screened published genomes for short, highly polymorphic targets and a 30-SNP barcode. We validated multiplexed amplification and sequencing using a portable Oxford Nanopore Technologies MinION sequencer on 28 clinical infections from four southern Thai provinces collected between 2018-2023. Twenty-seven loci yielded sequence data and 23 infections with data from at least eight loci were retained for analysis. Across the 23 Thai infections and 104 published Malaysian genomes, 586 diverse SNPs were observed. The amplicon panel and 30-SNP barcode retained the major population structure observed in genome-wide data, including a clear distinction between Bornean and Peninsular Malaysian infections and two clusters in Borneo. Across newly sequenced Thai infections, 25 loci were diverse and showed substantial diversity (mean expected heterozygosity = 0.69). All infections were effectively monoclonal. Pairwise identity-by-descent revealed substantial recent relatedness, with 46 of 253 pairs at or above 0.5. Two Thai genetic groups (n = 12 and n = 11) were observed, mirroring previously observed structure in peninsular Malaysia. Groups were not significantly associated with province or collection year. In conclusion, targeted sequencing can reveal geographically informative population structure across scales and thus support surveillance.

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Detection and Characterization of Human Bocavirus in Stool Samples from an Acute Gastroenteritis Outbreak in Salvador, Bahia, Brazil, in 2024.

Vidal, B.; Neves, S. O.; Santos, I. P.; Sardi, S. I.; Campos, G. s.

2026-10-21 gastroenterology 10.64898/2026.10.19.26365916 medRxiv
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Introduction: Acute gastroenteritis (AGE) is a global public health problem and a major cause of mortality in low- and lower-middle-income countries. Human bocavirus (HBoV) is among the viral agents associated with this condition. Therefore, investigating the presence of HBoV in cases of AGE in Salvador, Bahia, as well as its prevalence and circulating strains, is important. Objective: To investigate the occurrence of HBoV infection during an AGE outbreak in Salvador. Methods: A total of 178 samples were analyzed for HBoV using nested polymerase chain reaction (nested PCR), and the amplification products were visualized by agarose gel electrophoresis. HBoV was detected in 5.7% of the samples analyzed. Conclusion: This study contributes to the understanding of HBoV epidemiology as a secondary agent associated with acute gastroenteritis during a norovirus outbreak in Salvador. Continued investigation and identification of the etiological agents involved in outbreaks are essential for evaluating the causes of AGE. These findings also highlight the need for broader diagnostic approaches and the importance of phylogenetic analysis for monitoring and controlling viral infections.

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Adenovirus as a Causative Agent of an Acute Gastroenteritis Outbreak in Salvador, Bahia, Brazil.

Vidal, B.; Neves, S.; Santos, I. P.; Sardi, S. I.; Campos, G. S.

2026-10-21 gastroenterology 10.64898/2026.10.19.26365929 medRxiv
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Introduction: Acute gastroenteritis (AGE) is a cause of childhood morbidity and may be associated with human adenovirus (HAdV) infection. This study aimed to investigate the occurrence of HAdV in fecal samples from children with AGE in Salvador, Bahia, Brazil, as well as to molecularly characterize the identified strains and evaluate their cytopathic effects in cell culture. Methods: A total of 131 samples were analyzed using the nested polymerase chain reaction (Nested-PCR) technique. Molecular characterization was performed through Sanger sequencing and phylogenetic analysis, while Vero cell cultures were used to investigate the occurrence of cytopathic effects. Results: Of the samples analyzed, 13 (9.9%) tested positive for HAdV, while 118 (90.1%) were negative. The highest detection frequency was observed in children aged three years or younger, particularly those under one year of age. Phylogenetic analysis identified variants related to HAdV-F41 and HAdV-B3, revealing genetic differences and distinct clustering patterns compared with reference sequences. In cell culture, cytopathic effects were observed four days after inoculation, although further analyses are required to confirm productive viral replication. Conclusion: These findings demonstrate the presence of HAdV in the samples studied and contribute to understanding its genetic diversity and circulation in Salvador, highlighting the importance of epidemiological surveillance and further studies on its role in the etiology of childhood AGE.

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Burden and factors associated with hospitalization among patients with chronic Diseases at a tertiary Hospital in Wolaita Zone, South Ethiopia: A Cross-sectional study

Koyra, H. C.; Belete, Y. W.; Kanche, Z. Z.; Desalegn, Z.; Koyra, M. M.

2026-10-16 public and global health 10.64898/2026.10.14.26365506 medRxiv
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Background Chronic diseases are the leading causes of illness, disability, and death worldwide, with a disproportionate burden in low- and middle-income countries. Hospitalization is a critical outcome in chronic disease management, reflecting disease severity, treatment failure, and healthcare utilization. However, data on hospitalization burden and its associated factors among chronic disease patients in Ethiopia, are limited. This study aimed to determine the rate of hospitalization and its associated factors among patients with chronic diseases attending a tertiary hospital in Wolaita Zone, South Ethiopia. Methods A facility-based cross-sectional study was conducted among 321 patients with chronic diseases attending the chronic follow-up clinic at Wolaita Sodo University Comprehensive Specialized Hospital from November to December 2022. Consecutive recruitment was used, with unique medical record numbers tracked to prevent double recruitment. Data were collected through structured questionnaires and medical record review. Negative binomial regression was used to identify factors associated with hospitalization rate, with incidence rate ratios (IRR) and 95% confidence intervals (CI) reported. A p-value < 0.05 was considered statistically significant. Results Of the 321 participants, 66% reported at least one hospitalization while on treatment, with a mean of 1.70 {+/-} 1.81 hospitalizations per patient. Drug discontinuation was the most frequently documented reason for hospitalization (39.5%), followed by disease complications (22.3%) and infections (11.7%). Multimorbidity was prevalent, with the majority (59.8%) had 2-3 conditions, and a mean of 2.40 {+/-} 1.02 chronic diseases per patient. Male sex was associated with a higher hospitalization rate, while regular physical exercise was associated with a lower number of hospitalizations. Conclusion This study found a high burden of hospitalization among chronic disease patients, with drug discontinuation being the leading documented reason. Male sex and regular physical exercise were significantly associated highlighting the need for medication adherence support programs and structured exercise programs integrated into routine chronic disease care, as well as gender-sensitive interventions.

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National incidence of coccidioidomycosis in the United States estimated through machine learning integration of epidemiological, veterinary, and socioecological data

Couper, L. I.; Camponuri, S. K.; Sykes, J. E.; Li, X.; Hubbard, A. E.; Bustamante, B. L. M.; Williamson, T.; Ruberto, I.; Sondermeyer-Cooksey, G.; Karmarkar, E. N.; Yu, A. T.; Heaney, A. K.; Head, J. R.; Remais, J. V.

2026-10-16 epidemiology 10.64898/2026.10.14.26365564 medRxiv
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Importance: Coccidioidomycosis, also known as Valley fever, is a serious fungal disease caused by inhaling Coccidioides spores aerosolized from the soil. Despite rising public health concern, the distribution and incidence of coccidioidomycosis in the US remain poorly characterized as not all states are required to report cases, and case under-ascertainment is presumed to be high, particularly outside of the endemic region. Objective: To estimate monthly, county-level coccidioidomycosis incidence across the US while accounting for widespread under-ascertainment. Design, Setting, and Participants: We integrated multisource data, including human cases diagnosed in electronic health records, serological testing of dogs, and ecological and sociodemographic predictors, in a machine learning model estimating monthly, county-level coccidioidomycosis incidence. The model was trained on surveillance data from Arizona and California from 2013 to 2023, then applied to predict incidence in states across the contiguous US over the same time period. Main Outcomes and Measures: Incidence of coccidioidomycosis at the monthly county level. Results: The model predicted coccidioidomycosis incidence from 2013 to 2023 for 3,108 counties from all states in the contiguous US. The model identified 60 counties in non-reporting states where predicted incidence was [&ge;]2 cases per 100,000 population (considered moderate to high incidence). In states with mandatory reporting outside of Arizona and California, the model predicted county-level incidence rates that were 28% higher (95% bootstrap interval, 0.1%-69.8%) than those captured in national surveillance, equating to a total of 608 potentially missed cases per year (95% bootstrap interval, 340-964). Conclusions and Relevance: In this cross-sectional study, the model quantified case under-ascertainment for coccidioidomycosis relative to Arizona and California, and highlighted the potential for alternative data sources to fill in gaps in mandatory reporting. Estimating incidence while accounting for under-ascertainment and non-reporting may help efforts to improve public and physician awareness and to detect emergence in new regions.

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Multi-omic and Survival Analysis of Acute Chest Syndrome Burden in Sickle Cell Disease

Kulshrestha, A.; Garrett, M. E.; Nouraie, S. M.; Machado, R. F.; Gordeuk, V. R.; Gladwin, M. T.; Telen, M. J.; Ashley-Koch, A. E.; NHLBI Trans-Omics for Precision Medicine (TOPMed),

2026-10-19 hematology 10.64898/2026.10.15.26365641 medRxiv
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Sickle cell disease (SCD) results from homozygosity or compound heterozygosity for a single point mutation in the beta hemoglobin gene. Despite carrying the same underlying causal mutation, patients exhibit highly heterogeneous clinical outcomes. Acute chest syndrome (ACS) is one of the leading causes of mortality in SCD. In this study, we aimed to identify genetic variants associated with ACS occurrence and recurrence (>5 episodes) in two SCD cohorts (OMG-SCD and Walk-PHaSST) of predominantly African ancestry and characterize their downstream molecular consequences. Although none of the SNPs reached the genome-wide threshold in the occurrence meta-analysis, we identified 40 independent genetic loci with p <10-5. However, the recurrence GWAS in OMG-SCD, which compared individuals with no prior history of ACS to individuals with a history of >5 episodes, identified one genome-wide significant locus along with 38 other independent loci with p <10-5. Survival analysis suggested lower survival probability among young ACS recurrence cases compared to controls or occurrence cases. Furthermore, molecular QTL analysis of ACS recurrence identified 42 SNP-protein and eight SNP-metabolite associations with p <10-3. Pathway and enrichment analysis identified secretory, platelet/hemostatic, and complement-mediated pathways, confirming the complex and heterogeneous pathophysiology of ACS. This study highlights the importance of a well-defined phenotype for identification of risk loci and elucidates the complex interplay of hemolytic, inflammatory, and cellular organization pathways that warrants further evaluation through large-scale multi-omic studies of SCD patients. Ultimately, the more extreme phenotype of ACS recurrence may be a more informative phenotype for analysis, risk prediction, and therapeutic targeting.

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Blood-based PhenoAge may reflect disease burden rather than biological aging in cancer

Simhal, A. K.; Lee, J.; Tan, K. S.; McCormick, P. J.; Fischer, G. W.; Scarpa, J. R.; Sapiro, G.; Mincer, J. S.

2026-10-19 oncology 10.64898/2026.10.15.26365671 medRxiv
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PhenoAge, a blood-based biological aging clock, is associated with cancer outcomes, a finding taken as evidence that biological aging shapes prognosis. In 3,067 patients undergoing primary tumor resection, PhenoAge acceleration rose with tumor stage. One or two of its eight blood components, differing by cancer type, carried the prognostic signal, and replacing its general-population weights with equal weights did not weaken it. In cancer, PhenoAge may reflect disease burden rather than biological aging.

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Longitudinal changes in motor network activity and connectivity in patients with suspected Transcient Ischemic Attack: an exploratory fMRI study

Charbonnier, G.; Bonnet, L.; Comte, A.; Medeiros de Bustos, E.; Lesourd, M.

2026-10-19 neurology 10.64898/2026.10.13.26365278 medRxiv
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Background and Objectives Transient ischemic attack (TIA) diagnosis is challenging because it relies mainly on clinical assessment and exclusion of common differential. Functional MRI (fMRI) may provide a diagnostic biomarker by detecting transient brain dysfunction not visible on conventional imaging. This pilot study aimed to characterize acute motor-task BOLD activation in patients with suspected DWI-negative TIA and compare functional patterns between confirmed TIA and alternative diagnoses. Secondary objectives were to assess longitudinal changes in activation and connectivity at 3 months. Methods In this prospective single-center study, adults presenting within 24 h of transient anterior-circulation neurological symptoms underwent conventional MRI and additional motor-task fMRI. Patients with acute DWI lesions were excluded. Final diagnosis was established after 3-month follow-up. Whole-brain analyses, individualized motor cortex region-of-interest (ROI) analyses, and generalized psychophysiological interaction (gPPI) connectivity analyses were performed during the acute phase and at 3 months. Results Eight patients were enrolled; six had complete longitudinal imaging data and were included in the final analyses. Final diagnoses were TIA (n=2), migraine aura (n=2), functional neurological disorder (n=1), and hypoglycemia (n=1). Whole-brain and ROI analyses showed reduced bilateral motor-related BOLD responses during the acute phase in both TIA patients and in the patient with hypoglycemia. In contrast, patients with migraine and functional neurological disorder exhibited less marked longitudinal changes. In TIA patients, motor cortex activation increased at 3 months, tending to normalize toward values observed in non-TIA participants. Connectivity analyses revealed heterogeneous patterns, but the 2 TIA patients demonstrated increased longitudinal connectivity between the motor cortex contralateral to symptoms and other sensorimotor regions, including supplementary motor, premotor, parietal, and postcentral cortices. Discussion These preliminary findings suggest that TIA may be associated with transient bilateral reductions in motor-network activity. Functional abnormalities appeared to improve over time, supporting the hypothesis of reversible network dysfunction. Although limited by the very small sample size, this study provides the first longitudinal assessment of emergency task-based fMRI in rigorously defined TIA and supports further investigation of acute functional MRI as a potential biomarker of transient cerebral dysfunction.

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When Words Sound Alike: Decoding Homophone Processing in Chinese Primary Progressive Aphasia

Tee, B. L.; Chen, T.-F.; Li-Ying, L. K.-C.; Chuang, Y.; Lo, R. Y.; Tsoh, J.; Chan, A. L.-T.; Wong, A.; Mok, V.; Yan, T. Y. C.; Lu, C. J.; Yu, Y.; Lee, Y.; Allen, I. E.; Leng, F.; Cheng, Y.-W.; Lin, C.-H.; Li, C.-H.; Chen, Y.; Zhou, G.; Ng, A.; Vonk, J.; Gorno-Tempini, M. L.

2026-10-19 neurology 10.64898/2026.10.16.26364895 medRxiv
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Chinese is one of the living languages with the highest homophone densities, making homophone processing a critical component of language comprehension and orthographic decoding, as well as an ideal model for examining its cognitive mechanisms. This study assessed mono- and bi-character homophone selection function in 129 Mandarin- and Cantonese-speaking participants, including 66 cognitively healthy individuals, 17 with semantic variant (sv) primary progressive aphasia (PPA), 23 with the nonfluent/agrammatic variant (nfv) PPA, and 23 with the logopenic variant (lv) PPA. All PPA variants showed impairment in homophone selection, with most significant deficits in svPPA and lvPPA. ROC analyses demonstrated its strong diagnostic utility for distinguishing PPA from controls. Voxel-based morphometry revealed that homophone performance correlated with gray-matter volume in left anterior and inferior temporal regions, with variant-specific patterns observed. These findings described the potential role of homophone selection in diagnosing PPA syndrome in Chinese speakers, illuminate crosslinguistic influences on language impairment in PPA, and provide novel insights into the cognitive processing of homophones.

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The Effect of Regionalization of Thoracic Surgery on Blood Transfusion at the Ottawa Hospital

Smith, J.; Smith, B.; Pittman, T.

2026-10-19 health economics 10.64898/2026.10.15.26365639 medRxiv
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This paper examines the impact of Cancer Care Ontario's regionalization of lung cancer surgery on blood transfusion use for thoracic surgery at The Ottawa Hospital. Using aggregate data scraped from the paper ''Changing trends in blood transfusion: an analysis of 244,013 hospitalizations'' by Shehata et al. (2014) we estimated the effect regionalization on the log mean number of blood transfusions among thoracic surgeons (who treat lung cancer), utilizing other surgical specialties as controls. We found that the average number of blood transfusions increased significantly among thoracic surgeons following the opening of a new cancer care centre at the hospital in December 2009, while control specialties showed no parallel change. Contextualizing these results in a modified ''population level'' treatment threshold model, it is argued that the main driver of this increase in blood transfusions among thoracic surgeons was due to the influx of less skilled thoracic surgeons to The Ottawa Hospital, and the closing of thoracic surgery units at smaller hospitals which was part of the broader regionalization process.

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The bystander effect: lesion spatial extent as a foundational artifact in Lesion Network Mapping

Edelman, S.; Elias, U.; Arzy, S.

2026-10-19 neurology 10.64898/2026.10.17.26365701 medRxiv
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Lesion network mapping (LNM) has provided a compelling framework in clinical neuroscience, linking focal brain damage at heterogeneous anatomical locations to shared functional networks across behavioural syndromes. Recently, the methodological specificity of LNM has come under discussion following observations that derived network maps tend to converge onto the normative connectome's generic degree distribution. While current efforts largely treat this convergence as a statistical inference challenge addressable via post-hoc spatial null models or individual-level analyses, we identify a foundational upstream measurement artifact operating within individual patients: the lesion "bystander effect". Because pathological lesions follow biological constraints rather than functional brain parcellations, a typical lesion encapsulates both a symptom-driving critical node and surrounding asymptomatic bystander tissue. By averaging connectivity profiles across the entire lesion mask, LNM mechanically dilutes focal clinical signals. Across empirical clinical cohorts, individual-level machine learning classifiers, synthetic within-cohort lesion unions, and whole-brain spherical simulations, we demonstrate that increasing lesion extent deterministically drives network maps toward the connectome degree vector following a mathematical power law. Fulfilling the clinical promise of LNM will therefore require computational strategies that isolate the causal functional core from surrounding bystander tissue prior to network projection.