medRxiv : the preprint server for health sciences最新文献

{"title":"A qualitative study of how maternal morbidities impact women's quality of life during pregnancy and postpartum in five countries in sub-Saharan Africa and South Asia.","authors":"Martha Abdulai, Priyanka Adhikary, Sasha G Baumann, Muslima Ejaz, Jenifer Oviya Priya, M Bridget Spelke, Victor Akelo, Kwaku Poku Asante, Bitanya M Berhane, Shruti Bisht, Ellen Boamah-Kaali, Gabriela Diaz-Guzman, Anne George Cherian, Zahra Hoodbhoy, Margaret P Kasaro, Amna Khan, Janae Kuttamperoor, Dorothy Lall, Gifta Priya Manohari, Sarmila Mazumder, Karen McDonnell, Mahya Mehrihajmir, Wilbroad Mutale, Winnie K Mwebia, Imran Nisar, Kennedy Ochola, Peter Otieno, Gregory Ouma, Piya Patel, Winifreda Phiri, Neeraj Sharma, Emily R Smith, Charlotte Tawiah, Natalie J Vallone, Allison C Sylvetsky","doi":"10.1101/2025.01.14.25320557","DOIUrl":"10.1101/2025.01.14.25320557","url":null,"abstract":"<p><strong>Aim: </strong>Maternal morbidities present a major burden to the health and well-being of childbearing women. However, their impacts on women's quality of life (QoL) are not well understood. This work aims to describe the extent to which the morbidities women experience during pregnancy and postpartum affect their QoL and identify any protective or risk factors.</p><p><strong>Methods: </strong>This qualitative study included pregnant and postpartum women in Kenya, Ghana, Zambia, Pakistan, and India. Data were collected between November 2023 and June 2024. Participants were selected via purposive sampling, with consideration of age, trimester, and time since delivery. A total of 23 focus group discussions with 118 pregnant and 88 late (≥6 months) postpartum participants and 48 in-depth interviews with early (≤6 weeks) postpartum participants were conducted using semi-structured guides developed by the research team. Data was analyzed using a collaborative inductive thematic approach.</p><p><strong>Results: </strong>Four overarching themes were identified across pregnancy and the postpartum period: (1) physical and emotional challenges pose a barrier to daily activities; (2) lack of social support detracts from women's QoL; (3) receipt of social support mitigates adverse impacts of pregnancy and postpartum challenges on QoL; and (4) economic challenges exacerbate declines in women's QoL during pregnancy and postpartum.</p><p><strong>Conclusions: </strong>Bodily discomfort and fatigue were near-universal experiences. Physical and emotional morbidities related to childbearing limited women's ability to complete daily tasks and adversely impacted their perceived QoL. Social and financial support from the baby's father, family and/or in-laws, community members, and healthcare providers are important to mitigate the impacts of pregnancy and postpartum challenges on women's health and well-being.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noncanonical EEG-BOLD coupling by default and in schizophrenia.","authors":"Michael S Jacob, Brian J Roach, Daniel H Mathalon, Judith M Ford","doi":"10.1101/2025.01.14.25320216","DOIUrl":"10.1101/2025.01.14.25320216","url":null,"abstract":"<p><p>Neuroimaging methods rely on models of neurovascular coupling that assume hemodynamic responses evolve seconds after changes in neural activity. However, emerging evidence reveals noncanonical BOLD (blood oxygen level dependent) responses that are delayed under stress and aberrant in neuropsychiatric conditions. To investigate BOLD coupling to resting-state fluctuations in neural activity, we simultaneously recorded EEG and fMRI in people with schizophrenia and psychiatrically unaffected participants. We focus on alpha band power to examine voxelwise, time-lagged BOLD correlations. Principally, we find diversity in the temporal profile of alpha-BOLD coupling within regions of the default mode network (DMN). This includes early coupling (0-2 seconds BOLD lag) for more posterior regions, thalamus and brainstem. Anterior regions of the DMN show coupling at canonical lags (4-6 seconds), with greater lag scores associated with self-reported measures of stress and greater lag scores in participants with schizophrenia. Overall, noncanonical alpha-BOLD coupling is widespread across the DMN and other non-cortical regions, and is delayed in people with schizophrenia. These findings are consistent with a \"hemo-neural\" hypothesis, that blood flow and/or metabolism can regulate ongoing neural activity, and further, that the hemo-neural lag may be associated with subjective arousal or stress. Our work highlights the need for more studies of neurovascular coupling in psychiatric conditions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRANSIENT ALTERATIONS IN THALAMO-CEREBELLAR FUNCTIONAL CONNECTIVITY IN PREMANIFEST HUNTINGTON'S DISEASE.","authors":"Melanie A Morrison, Jingwen Yao, Radhika Bhalerao, Angela Jakary, Julia Glueck, Theresa Driscoll, Michael D Geschwind, Alexandra B Nelson, Katherine L Possin, Christopher P Hess, Janine M Lupo","doi":"10.1101/2025.01.15.25320232","DOIUrl":"https://doi.org/10.1101/2025.01.15.25320232","url":null,"abstract":"<p><strong>Background: </strong>There are no disease modifying therapies for Huntington's disease (HD), a rare but fatal genetic neurodegenerative condition. To develop and test new management strategies, a better understanding of the mechanisms underlying HD progression is needed. Aberrant changes in thalamo-cortical and striato-cerebellar circuitry have been observed in asymptomatic HD, along with transient enlargement of the dentate nucleus.</p><p><strong>Purpose: </strong>To evaluate the relationship between thalamo-cerebellar connectivity and HD progression.</p><p><strong>Study type: </strong>Prospective and retrospective.</p><p><strong>Population: </strong>Patients with HD and healthy controls from a single-center dataset (n=34), and patients from the public TRACK-HD dataset (n=91).</p><p><strong>Field strength/sequence: </strong>3T and 7T.</p><p><strong>Assessment: </strong>Thalamo-cerebellar connectivity was compared across patients and controls and related to motor scores and predicted years to symptom onset. Cross-sectional findings were validated within-patient by mapping changes in individual connectivity over time. HD effects on cognitive performance were also explored and related to connectivity.</p><p><strong>Statistical tests: </strong>Kruskal-Wallis with post hoc Dunn's tests and Pearson correlations (p _significant <0.05).</p><p><strong>Results: </strong>In the 7T cohort, significant premanifest and control group differences in thalamo-dentate connectivity were observed (p _Dunn <0.05, η ² =.19-.22), with manifest HD connectivity approaching normative values. Thalamic connectivity with the dentate nucleus and anterior cerebellum also correlated with years to onset (p _Den =0.06, r=0.42, p _Ant <0.05, r=-0.45), together indicating potential transient functional alterations in premanifest HD. Similar patterns were observed between connectivity (thalamus to dentate nucleus and anterior lobe) and cognitive performance scores across all subjects (p<0.05, r _Den =-0.17, r _Ant =-0.18). In the premanifest TRACK-HD cohort, connectivity of multiple thalamo-cerebellar connections correlated with years to onset, revealing distinct patterns for patients with low versus high motor scores, again indicative of potential transient alterations. Exploratory non-parametric regression of serial imaging data further supported these findings.</p><p><strong>Data conclusion: </strong>Transient changes in thalamo-cerebellar connectivity are seen in premanifest HD with increasing progression. More studies are needed to validate this potentially useful biomarker.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of plasma proteomic links to human organ imaging.","authors":"Zirui Fan, Julio Chirinos, Xiaochen Yang, Juan Shu, Yujue Li, Joan M O'Brien, Walter Witschey, Daniel J Rader, Ruben Gur, Bingxin Zhao","doi":"10.1101/2025.01.14.25320532","DOIUrl":"10.1101/2025.01.14.25320532","url":null,"abstract":"<p><p>Plasma protein levels provide important insights into human disease, yet a comprehensive assessment of plasma proteomics across organs is lacking. Using large-scale multimodal data from the UK Biobank, we integrated plasma proteomics with organ imaging to map their phenotypic and genetic links, analyzing 2,923 proteins and 1,051 imaging traits across multiple organs. We uncovered 5,067 phenotypic protein-imaging associations, identifying both organ-specific and organ-shared proteomic relations, along with their enriched protein-protein interaction networks and biological pathways. By integrating external gene expression data, we observed that plasma proteins associated with the brain, liver, lung, pancreas, and spleen tended to be primarily produced in the corresponding organs, while proteins associated with the heart, body fat, and skeletal muscle were predominantly expressed in the liver. We also mapped key protein predictors of organ structures and showed the effective stratification capability of plasma protein-based prediction models. Furthermore, we identified 8,116 genetic-root putative causal links between proteins and imaging traits across multiple organs. Our study presents the most comprehensive pan-organ imaging proteomics map, bridging molecular and structural biology and offering a valuable resource to contextualize the complex roles of molecular pathways underlying plasma proteomics in organ systems.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Hematopoiesis Associates with Prevalent and Incident Cardiometabolic Disease in High-Risk Individuals.","authors":"Jessica A Regan, Lydia Coulter Kwee, Navid A Nafissi, Alexander G Bick, William E Kraus, Pradeep Natarajan, Sidd Jaiswal, Svati H Shah","doi":"10.1101/2025.01.14.25320566","DOIUrl":"10.1101/2025.01.14.25320566","url":null,"abstract":"<p><strong>Background: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related presence of expanded somatic clones secondary to leukemogenic driver mutations and is associated with cardiovascular (CV) disease and mortality. We sought to evaluate relationships between CHIP with cardiometabolic diseases and incident outcomes in high-risk individuals.</p><p><strong>Methods: </strong>CHIP genotyping was performed in 8469 individuals referred for cardiac catheterization at Duke University (CATHGEN study) to identify variants present at a variant allele fraction (VAF) ≥2%. Associations were tested among any CHIP variant, large CHIP clones (VAF ≥10%) and individual CHIP genes with prevalent cardiometabolic traits. Cox proportional hazard models tested CHIP associations with time-to-overall mortality and Fine-Gray analyses tested CHIP associations with incident cardiovascular outcomes.</p><p><strong>Results: </strong>We identified 463 CHIP variants in 427 individuals (5.0%) of which 268 (3.2%) harbored large CHIP clones. CHIP and large CHIP were associated with lower odds of obesity (OR 0.79 [95% CI 0.65-0.98], p=0.03; OR 0.76 [95% CI 0.57-0.99], p=0.04, respectively). CHIP was associated with prevalent HF (OR 1.25 [95% CI 1.01 - 1.55], p=0.04; especially for non-<i>DNMT3A</i> CHIP (OR 1.38 [95% CI 1.04-1.82], p=0.02). CHIP was also associated with incident events: Non-<i>DNMT3A</i> CHIP was associated with increased risk of time-to-HF hospitalization (HR 1.29 [95% CI 1.02-1.63], p=0.03).</p><p><strong>Conclusions: </strong>In high-risk individuals referred for cardiac catheterization, large CHIP and non-<i>DNTM3A</i> CHIP were associated with obesity, prevalent HF, incident CV events. These findings strengthen the importance of CHIP as a biomarker for CV disease and highlight the contributing risk of large CHIP clones and non-<i>DNMT3A</i> CHIP variants.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiated HIV Service Delivery vs Conventional Care: Tuberculosis Preventive Therapy Outcomes for People Living with HIV in Sub-Saharan Africa.","authors":"Ann Johnson, Lucy Chimoyi, Salome Charalambous, Nicole Kawaza, Chris J Hoffmann, J Lucian Davis, Violet Chihota","doi":"10.1101/2025.01.15.25320590","DOIUrl":"10.1101/2025.01.15.25320590","url":null,"abstract":"<p><strong>Introduction: </strong>Differentiated service delivery (DSD) models, which are mechanisms of HIV care that reduce provider visits and offer varied ART delivery methods, are scaling up across sub-Saharan Africa. It is unknown how the movement of patients to DSD models impacts services beyond ART, including the uptake and completion of tuberculosis preventive therapy (TPT).</p><p><strong>Methods: </strong>Using the RE-AIM framework, we analyzed data from Opt4TPT, a longitudinal cohort study examining TPT delivery in South Africa and Zimbabwe. We constructed multivariate logistic regression models to evaluate the association of receiving ART from a DSD model with the proportion of participants who initiated and completed TPT, as measured by electronic medication boxes. We constructed a Cox proportional hazards model to assess the association between DSD models and time to TPT initiation.</p><p><strong>Results: </strong>Among 1193 participants, 276 received ART through a DSD model, while 917 used the conventional model. Overall, 1035 (87%) initiated TPT, including 242 (88%) in DSD models and 793 (86%) in conventional models. Receiving ART from a DSD model was not significantly associated (OR 1.11, 95% CI 0.74-1.67, p = 0.61) with TPT initiation. DSD models had a significantly longer mean time to initiation (6.5 vs. 2.7 days, p = 0.01). Of the 731 (71%) participants with MERM box data, 356 (49%) completed TPT. Bivariate analysis showed significantly higher odds of completing TPT among those in DSD models (OR 1.53, 95% CI 1.06-2.21, p=0.024). This association was not significant in multivariate analysis after adjusting for demographic and clinical factors (OR 0.89, 95% CI 0.58-1.36, p=0.58).</p><p><strong>Conclusions: </strong>We found high TPT uptake in DSD and conventional models of care, indicating that TPT delivery in DSD models is feasible. We found low TPT completion in both models of care, showing a need to focus on improving TPT completion overall.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson Disease Neuropathological Comorbidities: Prevalences from Younger-Old to Older-Old, With Comparison to Non-Demented, Non-Parkinsonian Subjects.","authors":"Thomas G Beach, Geidy E Serrano, Erika D Driver-Dunckley, Lucia I Sue, Holly A Shill, Shyamal H Mehta, Christine M Belden, Ileana Lorenzini, Cecilia Tremblay, Parichita Choudhury, Alireza Atri, Charles H Adler","doi":"10.1101/2025.01.13.25319971","DOIUrl":"10.1101/2025.01.13.25319971","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Co-existing neuropathological comorbidities have been repeatedly reported to be extremely common in subjects dying with dementia due to Alzheimer disease. As these are likely to be additive to cognitive impairment, and may not be affected by molecularly-specific AD therapeutics, they may cause significant inter-individual response heterogeneity amongst subjects in AD clinical trials. Furthermore, while originally noted for the oldest old, recent reports have now documented high neuropathological comorbidity prevalences in younger old AD subjects, who are more likely to be included in clinical trials. Comorbid neuropathologies in subjects with Parkinson disease have received much less attention. As with AD, comorbidities may interfere with the evaluation of PD clinical trials. We have here examined the decadal-wise presence of multiple co-pathologies, and their clinical effects, in a series of autopsies of PD and control subjects from the Arizona Study of Aging and Neurodegenerative Disorders. Amyloid plaques were present in more than 40% of PD patients in their 60s, and in 85% of those in their 90s. Neurofibrillary tangles were present in PD, as in all elderly humans, from the 60s onwards, while Braak tangle stages of IV or greater, which are strongly associated with severe cognitive impairment, reached 40%, 50% and 60% in those subjects in their 70s, 80s and 90s, respectively. Both plaques and tangles were significant predictors of a lower MMSE score while greater CAA scores had borderline significance. None of these, however, were independently associated with a higher UPDRS score. The ApoE4 allele, while a known predictor of AD pathology, especially amyloid plaques, was not an independent predictor of function with either of these clinical measures, suggesting that its influence is largely mediated by the neuropathologies that it predisposes to. Non-AD tauopathies, including the major conditions of progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), as well as the microscopic changes of argyrophilic grains (ARG) and aging-related tau astrogliopathy (ARTAG), also co-existed with PD, especially ARG and ARTAG, which ranged between 20% and 40% across decades for the former and up to 80% for the latter; we did not find significant associations of either with final MMSE or UPDRS scores. We failed to find a significant association of limbic TDP-43 histopathology with either final MMSE score or final UPDRS motor score but our subjects were more heavily weighted with PD than those in prior studies and our cognitive correlate, limited to MMSE score, may have missed associations with cognitive domain subsets. We found several cerebrovascular pathologies to be predictors of both cognitive and motor impairment, including brain infarcts, circle of Willis atherosclerosis, and higher white matter rarefaction score. All of the investigated pathology types were common in the non-demented, non-parkinsonian control subjects, and all i","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Hormonal Contraceptives on HPV Dynamics in Adolescent Girls and Young Women: Insights from a Randomized Controlled Sub-Study in South Africa.","authors":"Ramla F Tanko, Ongeziwe Taku, Zizipho Z A Mbulawa, Keletso Phohlo, Iyaloo Konstantinus, Christina Balle, Tanya Pidwell, Anna-Ursula Happel, Katherine Gill, Linda-Gail Bekker, Heather B Jaspan, Anna-Lise Williamson, Jo-Ann S Passmore","doi":"10.1101/2025.01.14.25320519","DOIUrl":"https://doi.org/10.1101/2025.01.14.25320519","url":null,"abstract":"<p><strong>Objectives: </strong>Human papillomavirus (HPV) is the leading cause of cervical cancer, with adolescent girls and young women (AGYW) in sub-Saharan Africa carrying a disproportionately high burden of infection. Hormonal contraceptives may influence HPV acquisition, persistence, and clearance, but evidence remains inconclusive. This sub-study aimed to evaluate the impact of different hormonal contraceptives on HPV prevalence and genotype distribution in AGYW.</p><p><strong>Methods: </strong>Ninety-eight HIV-seronegative AGYW aged 15-19 years from South Africa were randomized to receive one of three hormonal contraceptive methods: norethisterone enanthate (Net-EN) injectable, combined oral contraceptive pills (COCPs), or the etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR). Cervical DNA samples were collected at baseline and after 16 weeks for HPV genotyping using the HPV Direct Flow Chip test. HPV prevalence, persistence, clearance, and acquisition were analyzed across contraceptive methods.</p><p><strong>Results: </strong>At baseline, HPV prevalence was high (94.9%), with no differences among contraceptive arms. After 16 weeks, HPV prevalence remained high (89.5%) across groups. No significant differences were observed in overall HPV prevalence or genotype distribution by contraceptive method. Longitudinal analysis revealed that AGYW using Net-EN tended to have a higher cumulative number of high-risk HPV (HR-HPV) genotypes that cleared whereas those using CCVR acquired more HR-HPV types and had greater HR-HPV persistence compared to other groups.</p><p><strong>Conclusions: </strong>This study highlights the high burden of HPV among South African AGYW. However, different hormonal contraceptive methods did not significantly influence HR-HPV dynamics.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of Indigenous American-like ancestry on risk of acute lymphoblastic leukemia in Hispanic/Latino children.","authors":"Jalen Langie, Tsz Fung Chan, Wenjian Yang, Alice Y Kang, Libby Morimoto, Daniel O Stram, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Joseph L Wiemels, Jun J Yang, Adam J de Smith, Charleston W K Chiang","doi":"10.1101/2025.01.14.25320563","DOIUrl":"10.1101/2025.01.14.25320563","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Genetic variants, particularly ones found enriched in Indigenous American (IA)-like ancestry and inherited by Hispanics/Latinos, may contribute to this disparity. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and the frequency and effect size of known risk alleles in a large cohort of self-reported Hispanic/Latino individuals. We also performed genome-wide admixture mapping analysis to identify potentially novel ALL risk loci. We found that global IA ancestry was positively associated with ALL risk, but the association was not significant after adjusting for socio-economic indicators. In a series of local ancestry analyses, we uncovered that at known ALL risk loci, increasing copies of the IA-like haplotype were positively and significantly associated with ALL case-control status. Further, the IA-like haplotype had ~1.33 times the odds of harboring the risk allele compared to non-IA-like haplotypes. We found no evidence of interaction between genotype and ancestry (local or global) in relation to ALL risk. Admixture mapping identified association signals on chromosomes 2 (2q21.2), 7 (7p12.2), 10 (10q21.2), and 15 (15q22.31); however, only the variants at 7p12.2 and 10q21.2 replicated in additional cohorts. Taken together, our results suggest that increased risk of ALL in Hispanic/Latino children may be conferred by higher frequency of risk alleles within IA-like ancestry, which can be leveraged as targets of new precision health strategies and therapeutics.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPIRIT-CONSORT-TM: a corpus for assessing transparency of clinical trial protocol and results publications.","authors":"Lan Jiang, Colby J Vorland, Xiangji Ying, Andrew W Brown, Joe D Menke, Gibong Hong, Mengfei Lan, Evan Mayo-Wilson, Halil Kilicoglu","doi":"10.1101/2025.01.14.25320543","DOIUrl":"10.1101/2025.01.14.25320543","url":null,"abstract":"<p><p>Randomized controlled trials (RCTs) can produce valid estimates of the benefits and harms of therapeutic interventions. However, incomplete reporting can undermine the validity of their conclusions. Reporting guidelines, such as SPIRIT for protocols and CONSORT for results, have been developed to improve transparency in RCT publications. In this study, we report a corpus of 200 RCT publications, named SPIRIT-CONSORT-TM, annotated for transparency. We used a comprehensive data model that includes 83 items from SPIRIT and CONSORT checklists for annotation. Inter-annotator agreement was calculated for 30 pairs. The dataset includes 26,613 sentences annotated with checklist items and 4,231 terms. We also trained natural language processing (NLP) models that automatically identify these items in publications. The sentence classification model achieved 0.742 micro-F1 score (0.865 at the article level). The term extraction model yielded 0.545 and 0.663 micro-F1 score in strict and lenient evaluation, respectively. The corpus serves as a benchmark to train models that assist stakeholders of clinical research in maintaining high reporting standards and synthesizing information on study rigor and conduct.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}