bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the choice of stepping intensity metric influence dose-response associations with mortality? A UK population cohort study of 70,174 adults
Authors: Wei Le , Ahmadi Matthew N. , Blodgett Joanna M. , Aguiar Elroy J. , Biswas Raaj Kishore , Bozo Cruz Borja del , Stamatakis Emmanuel 
Published: September 2024

AbstractBackgroundResearch on the health effects of stepping intensity in free-living environments is limited and inconclusive. Inconsistent use of stepping intensity estimation metrics could explain current equivocal results. We aimed to examine and compare a range of different cadence-based metrics in terms of their multivariable-adjusted associations with all-cause (ACM) cardiovascular disease (CVD), cancer and physical-activity (PA)-related cancer mortality.MethodsThis prospective cohort study included participants with valid wrist-worn accelerometer data from the UK Biobank. We estimated stepping intensity using ten different cadence-based metrics, including eight peak-cadence metrics (defined as averaged steps / min of the highest but not necessarily consecutive minutes) that most of whom have appeared in prior literature, plus two non-peak-cadence metrics: 1) average daily cadence, defined as steps/accelerometer wearing mins, and 2) average cadence of purposeful steps, defined as averaged steps / min of minutes with ≥40 steps. We rescaled each metric into a standardised cadence scale with mean of 0 and standard deviation (SD) of 1, using (absolute–mean)/SD. We compared the dose-response associations of each stepping intensity estimation metrics with mortality outcomes using previously published modelling involving Cox-restricted-cubic-spline model, presented as overlay plots on standardised and absolute cadence scales.ResultsAmong 70,336 participants (age [SD], 61.6 [7.8] years; female, 40,933 [58%]) followed up for a median of 8.0 years, all cadence-based metrics, besides the average cadence of purposeful steps, exhibited a comparable beneficial dose-response association with ACM/CVD/cancer mortality, with 95% CI largely overlapped (e.g., at −0.2 standardised steps/min, the hazard ratio (HR) of ACM for peak 1- and peak 30-min cadence were: 0.72, 95%CI [0.65, 0.82] and 0.66 [0.60, 0.73], respectively). The average cadence of purposeful steps only did not show dose-response associations with mortality outcomes (e.g., the HR that corresponds to the standardised median for the average cadence of purposeful steps in ACM was 0.98 [95% CI: 0.86, 1.12].ConclusionBesides the average cadence of purposeful steps, all stepping intensity estimation metrics demonstrated comparable beneficial dose-response associations with mortality of all-cause, CVD and cancer, suggesting these cadence-based metrics may be used interchangeably for estimating associations of free-living stepping intensity with health outcomes and applied in different research scenarios accordingly.
Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling
Authors: Bellissimo Christian J. , Yeo Erica , Ribeiro Tatiane A. , Jazwiec Patrycja A. , Ellewela Chethana , Bains Jaskiran , Ashkar Ali A. , Beristain Alexander G. , Bowdish Dawn M.E. , Sloboda Deborah M. 
Published: September 2024

AbstractExcess maternal adiposity (i.e., overweight and obesity) during pregnancy has been linked to impaired uteroplacental perfusion, compromised placental development, and a higher risk of adverse pregnancy outcomes. Owing to the nature of chronic inflammation and immune dysregulation accompanying excess adiposity, disruption of leukocyte-mediated tissue remodelling and immunoregulation within the decidua have emerged as likely drivers contributing to suboptimal placental function in pregnancies impacted by maternal overweight or obesity. However, the impacts of excess adiposity on major populations of innate lymphoid cells (ILCs) and macrophages which orchestrate these processes and the environment that these cells occupy remain vastly understudied. Here, we used a mouse model of chronic high-fat, high-sucrose (HFHS) diet-feeding to characterize the impacts of an obesogenic milieu on decidual immune dynamics during placental development at mid-gestation (E10.5). HFHS pregnancies exhibited marked increases in total decidual leukocyte abundance, driven by population-level increases in tissue-resident and conventional NK cells, and MHC-II+macrophages. This was not associated with abnormalities in implantation site morphology or decidual spiral artery remodelling but was coincident with histological patterns of local inflammation. In line with this, expression of canonical proinflammatory cytokines and chemokines were moderately upregulated in bulk decidual tissue of HFHS dams. This was accompanied by more potent elevations in multiple mediators of angiogenesis, endothelial activation, and coagulation in HFHS decidual tissue. Collectively, these findings point towards pathological vascular inflammation and possibly dysregulated decidual angiogenesis in the first half of pregnancy as factors predisposing to reduced placental efficiency, malperfusion, and inflammation seen in pregnancies affected by maternal overweight and obesity.
Measurable imaging-based changes in enhancement of intrahepatic cholangiocarcinoma after radiotherapy reflect physical mechanisms of response
Authors: De Brian , Dogra Prashant , Zaid Mohamed , Elganainy Dalia , Sun Kevin , Amer Ahmed M. , Wang Charles , Rooney Michael K. , Chang Enoch , Kang Hyunseon C. , Wang Zhihui , Bhosale Priya , Odisio Bruno C. , Newhook Timothy E. , Tzeng Ching-Wei D. , Cao Hop S. Tran , Chun Yun S. , Vauthey Jean-Nicholas , Lee Sunyoung S. , Kaseb Ahmed , Raghav Kanwal , Javle Milind , Minsky Bruce D. , Noticewala Sonal S. , Holliday Emma B. , Smith Grace L. , Koong Albert C. , Das Prajnan , Cristini Vittorio , Ludmir Ethan B. , Koay Eugene J. 
Published: September 2024

AbstractBackgroundAlthough escalated doses of radiation therapy (RT) for intrahepatic cholangiocarcinoma (iCCA) are associated with durable local control (LC) and prolonged survival, uncertainties persist regarding personalized RT based on biological factors. Compounding this knowledge gap, the assessment of RT response using traditional size-based criteria via computed tomography (CT) imaging correlates poorly with outcomes. We hypothesized that quantitative measures of enhancement would more accurately predict clinical outcomes than size-based assessment alone and developed a model to optimize RT.MethodsPre-RT and post-RT CT scans of 154 patients with iCCA were analyzed retrospectively for measurements of tumor dimensions (for RECIST) and viable tumor volume using quantitative European Association for Study of Liver (qEASL) measurements. Binary classification and survival analyses were performed to evaluate the ability of qEASL to predict treatment outcomes, and mathematical modeling was performed to identify the mechanistic determinants of treatment outcomes and to predict optimal RT protocols.ResultsMultivariable analysis accounting for traditional prognostic covariates revealed that percentage change in viable volume following RT was significantly associated with OS, outperforming stratification by RECIST. Binary classification identified ≥33% decrease in viable volume to optimally correspond to response to RT. The model-derived, patient-specific tumor enhancement growth rate emerged as the dominant mechanistic determinant of treatment outcome and yielded high accuracy of patient stratification (80.5%), strongly correlating with the qEASL-based classifier.ConclusionFollowing RT for iCCA, changes in viable volume outperformed radiographic size-based assessment using RECIST for OS prediction. CT-derived tumor-specific mathematical parameters may help optimize RT for resistant tumors.
Shortened SARS-CoV-2 shedding in saliva during early Omicron compared to wild-type pandemic phase
Authors: Kozanli Eva , Winkel Angelique M.A.M. , Han Alvin X. , van den Brink Sharon , van den Brandt Annemarie , Haverkort Milly E. , Euser Sjoerd , Russell Colin A. , de Jong Menno D. , van Houten Marlies A. , van Lelyveld Steven F.L. , Eggink Dirk 
Published: September 2024

AbstractThis study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens duration of viral shedding and lowers viral load peaks. Dense saliva sampling can be a convenient tool to study viral load dynamics.
Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery: a multi-ancestry study in 10 960 individuals from 9 biobanks
Authors: German Jakob , Cordioli Mattia , Tozzo Veronica , Urbut Sarah , Arumäe Kadri , Smit Roelof A.J. , Lee Jiwoo , Li Josephine H. , Janucik Adrian , Ding Yi , Akinkuolie Akintunde , Heyne Henrike , Eoli Andrea , Saad Chadi , Al-Sarraj Yasser , Abdel-latif Rania , Mohammed Shaban , Al Hail Moza , Barry Alexandra , Wang Zhe ,   Estonian Biobank research team, Cajuso Tatiana , Corbetta Andrea , Natarajan Pradeep , Ripatti Samuli , Philippakis Anthony , Szczerbinski Lukasz , Pasaniuc Bogdan , Kutalik Zoltan , Mbarek Hamdi , Loos Ruth J.F. , Vainik Uku , Ganna Andrea 
Published: September 2024

AbstractObesity is a significant public health concern. GLP-1 receptor agonists (GLP1-RA), predominantly in use as a type 2 diabetes treatment, are a promising pharmacological approach for weight loss, while bariatric surgery (BS) remains a durable, but invasive, intervention. Despite observed heterogeneity in weight loss effects, the genetic effects on weight loss from GLP1-RA and BS have not been extensively explored in large sample sizes, and most studies have focused on differences in race and ethnicity, rather than genetic ancestry. We studied whether genetic factors, previously shown to affect body weight, impact weight loss due to GLP1-RA therapy or BS in 10,960 individuals from 9 multi-ancestry biobank studies in 6 countries. The average weight change between 6 and 12 months from therapy initiation was -3.93% for GLP1-RA users, with marginal differences across genetic ancestries. For BS patients the weight change between 6 and 48 months from the operation was -21.17%. There were no significant associations between weight loss due to GLP1-RA and polygenic scores for BMI or type 2 diabetes or specific missense variants in theGLP1R, PCSK1 and APOEgenes, after multiple-testing correction. A higher polygenic score for BMI was significantly linked to lower weight loss after BS (+0.7% for 1 standard deviation change in the polygenic score, P = 1.24×10-4), but the effect was modest and further reduced in sensitivity analyses. Our findings suggest that existing polygenic scores related to weight and type 2 diabetes and missense variants in the drug target gene do not have a large impact on GLP1-RA effectiveness. Our results also confirm the effectiveness of these treatments across all major continental ancestry groups considered.
Cross-EHR validation of antidepressant response algorithm and links with genetics of psychiatric traits
Authors: Sealock Julia M. , Tubbs Justin D. , Lake Allison M. , Straub Peter , Smoller Jordan W. , Davis Lea K. 
Published: September 2024

AbstractObjectiveAntidepressants are commonly prescribed medications in the United States, however, factors underlying response are poorly understood. Electronic health records (EHRs) provide a cost-effective way to create and test response algorithms on large, longitudinal cohorts. We describe a new antidepressant response algorithm, validation in two independent EHR databases, and genetic associations with antidepressant response.MethodWe deployed the algorithm in EHRs at Vanderbilt University Medical Center (VUMC), the All of Us Research Program, and the Mass General Brigham Healthcare System (MGB) and validated response outcomes with patient health questionnaire (PHQ) scores. In a meta-analysis across all sites, worse antidepressant response associated with higher PHQ-8 scores (beta = 0.20, p-value = 1.09 x 10−18).ResultsWe used polygenic scores to investigate the relationship between genetic liability of psychiatric disorders and response to first antidepressant trial across VUMC and MGB. After controlling for depression diagnosis, higher polygenic scores for depression, schizophrenia, bipolar, and cross-disorders associated with poorer response to the first antidepressant trial (depression: p-value = 2.84 x 10−8, OR = 1.07; schizophrenia: p-value = 5.93 x 10−4, OR = 1.05; bipolar: p-value = 1.99 x 10−3, OR = 1.04; cross-disorders: p-value = 1.03 x 10−3, OR = 1.05).ConclusionsOverall, we demonstrate our antidepressant response algorithm can be deployed across multiple EHR systems to increase sample size of genetic and epidemiologic studies of antidepressant response.
Comparison of visual function analysis of people with low vision using three different models of augmented reality devices
Authors: Gopalakrishnan Sarika , Kartha Arathy , Schuchard Ronald , Fletcher Donald 
Published: September 2024

AbstractWe compared visual function in individuals with low vision (>20/60) using three different models of augmented reality (AR) devices: Ziru, IrisVision, and NuEyes-Pro3. The distance visual acuity (VA) was measured in high luminance high contrast (HLHC), high luminance low contrast (HLLC), low luminance high contrast (LLHC), and low luminance low contrast (LLLC) settings. The other tests were near VA, distance and near contrast sensitivity (CS), color vision, depth perception and indoor navigation. The change in visual function without and with AR devices was analyzed. Out of 27 participants, 17 were female. The mean age was 66.7±18.2 years. The median baseline VA was 0.66 (0.49) logMAR in HLHC, 0.87 (0.54) logMAR in HLLC, 0.84 (0.67) logMAR in LLHC and 1.04 (0.34) logMAR in LLLC. The median baseline near VA was 0.55(0.4) logMAR, distance and near CS was 1.10(0.26) logCS, and 1.20(0.30) logCS respectively. Distance and near vision showed significant differences with both Ziru and IrisVision (p<0.01), but not with NuEyes. There was a significant change in CS using Ziru and IrisVision for both distance and near (p<0.05) but both reduced significantly with NuEyes (p<0.01). The baseline functional vision score (FVS) was 45.76 (44.47) which improved to 79.04 (33.98) with Ziru and 76.14 (33.76) with IrisVision significantly, whereas it significantly reduced to 35.00 (33.97) with NuEyes (p<0.01). During the objective identification task on the indoor mobility course using AR devices, head-level objects were missed more compared to waist or floor-level objects across all three models. Majority of the visual functions improved with Ziru and IrisVision, with limited improvement in certain lighting condition of distance visual acuity with NuEyes.
Proteogenomic signature of risk of Alzheimer’s disease and related dementia risk in individuals with a history of major depression disorder
Authors: Diniz Breno Satler , Chen Zhiduo , Steffens David C. , Pilling Luke , Fortinsky Richard H. , Kuchel George A. , Kuo Chia-Ling 
Published: September 2024

AbstractThe mechanisms linking a history of major depressive disorder (MDD) to an increased risk of Alzheimer’s disease and related dementia (ADRD) are not fully understood. Using the UK Biobank available proteomic and genomic data, we evaluated the biological mechanisms linking both conditions. In participants with a history of MDD at baseline (n=3,615), we found that plasma levels of NfL, GFAP, PSG1 were associated with higher risk (HR=1.38; 1.37; 1.34, respectively; all adjusted p-values<0.05), while VGF, GET3, and HPGDS were associated with lower risk of incident ADRD (n=150) (HR=0.73; 0.71; 0.66, respectively; all adjusted p-values<0.05) during a mean follow-up of 13.7 years (SD=2.2). Two-sample Mendelian randomization analysis using cis-pQTLs genetic instruments revealed that a lower protein expression of apolipoprotein E and higher IL-10 receptor subunit B were causally linked to incident ADRD. Finally, we developed a Proteomic Risk Score (PrRSMDD-ADRD), which showed strong discriminative power (C-statistic = 0.84) to identify participants with MDD that developed ADRD upon follow-up. In addition to demonstrating an association between plasma proteins associated with inflammation and future ADRD risk in individuals with MDD, our findings include an element of causality using Mendelian Randomization (MR) and PrRSMDD-ADRDcan be useful to identify individuals with the highest risk to develop ADRD in a highly vulnerable population.
Machine learning for the prediction of spontaneous preterm birth using early second and third trimester maternal blood gene expression: A Cautionary Tale
Authors: Hornaday Kylie K , Werbicki Ty , Tough Suzanne C , Wood Stephen L , Anderson David W , Slater Donna M 
Published: September 2024

AbstractPreterm birth (PTB) remains a significant global health challenge and a leading cause of neonatal mortality and morbidity. Despite advancements in neonatal care, the prediction of PTB remains elusive, in part due to complex etiologies and heterogeneous patient populations. This study aimed to validate and extend information on gene expression biomarkers previously described for predicting spontaneous PTB (sPTB) using maternal whole blood from the All Our Families pregnancy cohort study based in Calgary, Canada. The results of this study are two-fold: first, using additional replicates of maternal blood samples from the All Our Families cohort, we were unable to repeat the findings of a 2016 study which identified top maternal gene expression predictors for sPTB. Second, we conducted a secondary analysis of the original gene expression dataset from the 2016 study, including external validation using a pregnancy cohort based in Detroit, USA. While initial results of our machine learning model suggested promising performance (area under the receiver operating curve, AUC 0.90 in the training set), performance was significantly degraded on the test set (AUC 0.54), and further degraded in external validation (AUC 0.51), suggesting poor generalizability, likely due to overfitting exacerbated by a low feature-to-noise ratio. Prediction was not improved when using machine learning approaches over traditional statistical learning. These findings underscore the challenges in translating biomarker discovery into clinically useful predictive models for sPTB. This study highlights the critical need for rigorous methodological safeguards and external validation in biomarker research. It also emphasizes the impact of data noise and overfitting on model performance, particularly in high-dimensional omics datasets. Future research should prioritize robust validation strategies and explore mechanistic insights to improve our understanding and prediction of PTB.
Malaria prevalence and its associated factors amongst rural adults: Cross-sectional study in East Nusa Tenggara Province Indonesia
Authors: Guntur Robertus Dole , Pahnael Jusrry Rosalina , Ginting Keristina Br , Bria Yulianti Paula , Kusumaningrum Damai , Islam Fakir M Amirul 
Published: September 2024

AbstractIntroductionMalaria is a global health issue including in Indonesia. Currently, most of the cases was in the rural of eastern part of the country. However, malaria risk factors amongst rural adult were less documented. This study investigated malaria risk factors amongst rural adults in East Nusa Tenggara Province (ENTP).MethodsA community based cross-sectional study was conducted to interview 1495 rural adults in ENTP. A multi-stage cluster random sampling technique was applied to collect data on malaria history, demographic, behavioural and environmental factors of malaria of participants. Logistic regression model was applied to decide significant factors associated with malaria.ResultsThe prevalence of malaria was 13.4%. The prevalence of malaria was significantly higher for adults with low level of malaria knowledge (Adjusted odd ratio (AOR): 2.43, 95% confidence interval (CI): 1.38 – 4.27) compared to those with high malaria knowledge level, having moderate malaria knowledge level (AOR: 1.99, 95% CI: 1.11 – 3.57) compared to those high malaria knowledge level, having no education (AOR: 2.18, 95% CI: 1.37 – 3.45) compared to those junior high school or above education level, outdoor occupation (AOR: 1.81, 95% CI: 1.22 – 2.68) compared to indoor occupation, having family size > 4 (AOR 2.08, 95% CI: 1.52 –2.87) compared to those ≤ 4ConclusionThe study revealed the prevalence of malaria amongst rural adults in this province was high. The study highlights the power of malaria knowledge level on the prediction of malaria prevalence amongst rural adults. Health education intervention is critical for vulnerable groups to reduce malaria prevalence in the province.
Proteostasis and metabolic dysfunction in a distinct subset of storage-induced senescent erythrocytes targeted for clearance
Authors: Peltier Sandy , Marin Mickaël , Dzieciatkowska Monika , Dussiot Michaël , Roy Micaela Kalani , Bruce Johanna , Leblanc Louise , Hadjou Youcef , Georgeault Sonia , Fricot Aurélie , Roussel Camille , Stephenson Daniel , Casimir Madeleine , Sissoko Abdoulaye , Paye François , Dokmak Safi , Ndour Papa Alioune , Roingeard Philippe , Gautier Emilie-Fleur , Spitalnik Steven L , Hermine Olivier , Buffet Pierre A , D’Alessandro Angelo , Amireault Pascal 
Published: September 2024

AbstractAlthough refrigerated storage slows the metabolism of volunteer donor RBCs, cellular aging still occurs throughout thisin vitroprocess, which is essential in transfusion medicine. Storage-induced microerythrocytes (SMEs) are morphologically-altered senescent RBCs that accumulate during storage and which are cleared from circulation following transfusion. However, the molecular and cellular alterations that trigger clearance of this RBC subset remain to be identified. Using a staining protocol that sorts long-stored SMEs (i.e., CFSEhigh) and morphologically-normal RBCs (CFSElow), thesein vitroaged cells were characterized.Metabolomics analysis identified depletion of energy, lipid-repair, and antioxidant metabolites in CFSEhighRBCs. By redox proteomics, irreversible protein oxidation primarily affected CFSEhighRBCs. By proteomics, 96 proteins, mostly in the proteostasis family, had relocated to CFSEhighRBC membranes. CFSEhighRBCs exhibited decreased proteasome activity and deformability; increased phosphatidylserine exposure, osmotic fragility, and endothelial cell adherence; and were cleared from the circulation during human spleenex vivoperfusion. Conversely, molecular, cellular, and circulatory properties of long-stored CFSElowRBCs resembled those of short-stored RBCs.CFSEhighRBCs are morphologically and metabolically altered, have irreversibly oxidized and membrane-relocated proteins, and exhibit decreased proteasome activity.In vitroaging during storage selectively alters metabolism and proteostasis in SMEs, targeting these senescent cells for clearance.