bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health of first- and second-generation immigrant children in England and Wales: serial, cross-sectional study using linked Census and birth registration data
Authors: Hardelid Pia , Yu Senhao , Stockton Jemima , Langella Rebecca , Lewis Kate 
Published: February 2025

IntroductionThere is limited research on the health outcomes of children who have migrated, or whose parents have migrated, to the UK.MethodsWe used linked birth registration and Census data from the 1991, 2001 and 2011 waves of the Longitudinal Study, covering 1% of the England and Wales population. We derived the prevalence of self-or-caregiver reported limiting long-term illness (2001, 2011 Censuses) and poor health (1991, 2001, 2011 Censuses) among household members <18 years old. We defined immigration background using child and parent country of birth. Logistic regression models assessed the association between immigration background and health outcomes.ResultsThe percentage of children who were first-or second-generation immigrants increased from 16.6% (20120/121109) in 1991 to 24.7% (28965/117116) in 2011. We found no evidence of an association between immigration background and health outcomes in 1991. In 2011, children born outside the UK were less likely to report a limiting long-term illness (odds ratio 0.67; 95% confidence interval 0.58, 0.76) compared to average. Also in 2011, children born in the UK to UK-born parents or non-UK-born fathers/UK-born mothers had higher odds of reporting long-term illness compared to average (1.25; 1.17, 1.32 and 1.21; 1.08, 1.36, respectively). In both 2001 and 2011, children born in the UK to non-UK-born parents had the highest odds of reporting poor health.ConclusionWhilst immigrant children with a first-generation immigrant background are less likely to live with limiting long-term illness, evidence-based National Health Service guidelines for supporting second-generation immigrant children are needed.What is already known on this topicStudies of adults have identified a ‘healthy migrant effect’, where immigrants have lower mortality rates than the host population.It is not clear if this applies to children or to non-mortality outcomes.What this study addsThere was no association between children’s immigration background and prevalence of long-term illness before 2011, or poor health before 2001.First generation immigrant children had lower prevalence of limiting long-term illness, and similar prevalence of poor health to non-immigrant children.Children born in the UK to UK-born parents or second-generation immigrant children via the father had higher prevalence of long-term illness, and UK-born children whose parents were both born abroad had higher prevalence of poor health.How this study might affect research, practice or policyThe National Health Service should develop evidence-based guidelines for how health services can support second generation immigrant children.
Persistent articular infection and host reactive response contribute toBrucella-induced spondyloarthritis in SKG mice
Authors: Harms Jerome S. , Lasarev Michael , Warner Thomas , Costa Oliveira Sergio , Smith Judith A. 
Published: February 2025

AbstractBrucellosis, one of the most prevalent zoonotic diseases worldwide, often results in osteoarticular complications including large joint and axial arthritis mimicking spondyloarthritis. To model this chronic manifestation, we infected autoimmunity-prone SKG mice containing a mutation in the T-cell adaptor ZAP-70 withBrucellaspecies.B. melitensisinfection resulted in a fully penetrant, readily scoreable disease involving large joint wrist and foot arthritis, peri-ocular inflammation, and less frequent scaly paw rash. Infection withB. abortusresulted in delayed arthritis onset, andB. neotomaerevealed sex differences, with more severe disease and a dose response in females. Heat-killedBrucelladid not induce arthritis, evincing a requirement for viable infection. Across species, splenic CFU correlated well with final clinical score at 12 weeks (ρ=0.79 and p<0.001).In vivoimaging using luminescentB. neotomaerevealed rapid colonization of the paws by one-week post-infection, more than a month prior to arthritis onset. Paw luminescence levels decreased after 2 weeks and then remained relatively static, even as clinical scores increased. Thus, the degree of arthritis did not strictly correlate with degree of paw infection but suggested an additional reactive component. Further, in examining aBrucellaΔtcpBmutant lacking a Type IV secretion system-dependent mediator, mice displayed an intermediate phenotype without significant differences in splenic CFU. Together these data suggestBrucellainduced spondyloarthritis reflects both persistent colonization as well as excess host reactivity. Moreover, the sensitivity of the SKG model to different species and mutants will provide new opportunities for dissecting correlates ofBrucellavirulence and host immunity.ImportanceBrucellosis, a bacterial infection acquired from herd animals, remains one of the most common zoonotic diseases worldwide. Chronic infection often results in spondyloarthritis-like complications. Investigation into pathogenesis has been limited by the lack of overt disease in standard lab mice. We addressed this issue using spondyloarthritis-susceptible SKG mice. Upon infection withB. melitensis, SKG mice develop robust, fully penetrant large joint arthritis. Arthritis development required viable bacteria. Moreover, studies of colonization, gene expression and anatomic distribution using bioluminescent bacteria revealed active persistent infection in the mouse paws. However, peak paw infection occurred much earlier than arthritis onset, suggesting an added immune reactive component. Disease onset, severity and manifestations varied upon infection with differentBrucellaspecies and mutants. Together these results suggest this new model will be very useful to the scientific community for determining correlates of bacterial virulence leading to clinical disease.
Estimates of underlying health biases in SARS-CoV-2 vaccination recipients: a nationwide study in previously-infected adults
Authors: Riedmann Uwe , Chalupka Alena , Richter Lukas , Werber Dirk , Sprenger Martin , Willeit Peter , Rijksen Marc , Lodron Julia , Høeg Tracy Beth , Ioannidis John PA , Pilz Stefan 
Published: February 2025

AbstractBackgroundObservational studies may over- or under-estimate SARS-CoV-2 vaccine effectiveness (VE) depending on whether healthier (i.e. healthy vaccine effect (HVE)) or more ill individuals are preferentially vaccinated. To evaluate this issue, we compared non-COVID-19, all-cause, cancer and COVID-19 mortality in vaccinated versus unvaccinated individuals.MethodsThis is a nationwide retrospective observational study in the entire adult population in Austria with previously documented SARS-CoV-2 infection with a follow-up from 2021 to 2023. Cox regression analyses were used to calculate hazard ratios (HRs) according to the number of SARS-CoV-2 vaccinations. We also performed matched analyses, where on each day, newly vaccinated individuals were matched with unvaccinated individuals based on age, sex and nursing home residency.ResultsOverall, 4,324,485 individuals (median age (IQR): 46 (33-59) years; 52.56% female) were eligible and 2.23 non-COVID-19 deaths occurred per 100,000 person days. Group differences in non-COVID-19 mortality risk were most prominent in the early periods (e.g., in Q4 2021, adjusted HRs (95% CI) in vaccinated versus unvaccinated were 0.69 (0.59 - 0.81), 0.65 (0.58 - 0.74), and 0.56 (0.48 - 0.66) for 1-, 2-, and 3-vaccinations, respectively) and decreased thereafter. Matched analyses for the first two weeks after vaccination showed HRs below 0.5 for vaccinated versus unvaccinated individuals irrespective of vaccination numbers. Similar findings were retrieved for non-COVID-19, all-cause, and cancer deaths. Overall, COVID-19 deaths were significantly reduced in vaccinated individuals.ConclusionsHVE for SARS-CoV-2 vaccines was strong early after vaccination and diminished over time. HVE should be considered when estimating VE.
Diabetes impact on nigrostriatal vulnerability in Parkinson’s Disease
Authors: Galli Alice , Zatti Cinzia , Lupini Alessandro , Caminiti Silvia Paola , Rizzardi Andrea , Lucchini Silvia , Bertagna Francesco , Paghera Barbara , Outeiro Tiago Fleming , Perani Daniela , Padovani Alessandro , Pilotto Andrea 
Published: February 2025

AbstractMechanisms underlying the role of diabetes mellitus (DM) as modulator of severity in Parkinson’s Disease (PD) remain unclear. Aim of this study was to investigate the impact of DM on nigrostriatal dopaminergic vulnerability considering two independent cohorts of drug-naïve PD patients (PPMI and DNA studies). Patients with and without DM were first compared and then matched for age, sex, symptoms severity. Differences in123I-FP-CIT binding and molecular connectivity alterations were tested in PD with and without DM within the nigrostriatal pathway. 269 drug-naïve patients were enrolled (PPMI, n=174; DNA, n=95). In both cohorts, patients with DM were older, predominantly male, and exhibited worse non-motor and cognitive symptoms. After severity-matching, patients with DM were found to exhibit more preserved dopamine binding in striatal regions compared to those without DM, together with a lower neural reserve. Patients with DM showed significant dopaminergic connectivity alterations (20%), primarily due to a loss of connectivity (98%). In contrast, patients without DM had more widespread connectivity changes (33%), characterized by both loss (84%) and gained connections (16%). These findings suggest that diabetes directly affects the nigrostriatal network, resulting in less deficits despite similar disease severity, perhaps decreasing the effect of reserve on dopaminergic neurons loss.
Common Genetic Variants Modify Disease Risk and Clinical Presentation in Monogenic Diabetes
Authors: Leech Jacques Murray , Beaumont Robin N , Arni Ankit M , Chundru V. Kartik , Sharp Luke N , Colclough Kevin , Hattersley Andrew T , Weedon Michael N , Patel Kashyap A 
Published: February 2025

AbstractThe contribution of polygenic background in young onset monogenic disorders needs further exploration. Understanding this will provide new biological insights and may improve risk prediction of monogenic disease. Here we investigated the role of polygenic background in MODY—a common monogenic disorder with an age-dependent onset.We found strong enrichment of type 2 diabetes (T2D) polygenic risk, but not type 1 diabetes risk, in genetically confirmed MODY cases. This T2D polygenic burden, primarily through beta-cell dysfunction pathways, was strongly associated with earlier age of diagnosis and increased diabetes severity. Common genetic variants collectively accounted for 24% (p<0.0001) of the phenotypic variability. Using a large population cohort, we demonstrated that T2D polygenic burden substantially modifies diabetes onset in individuals with pathogenic variants, with diabetes risk ranging from 11% to 81%. Finally, we show that individuals with MODY-like phenotypes without a causal variant had elevated polygenic burden for T2D and related traits representing potential polygenic phenocopies. These findings reveal substantial influence of common genetic variation in shaping the clinical presentation of early-onset monogenic disorders. Incorporating these may improve risk estimates for individuals carrying pathogenic monogenic variants.
Analyzing concordance between MUAC, MUACZ, and WHZ in diagnosing acute malnutrition among children under 5 in Somalia
Authors: Garretson Sydney , Walton Shelley , Alier Kemish Kenneth , Grounds Samantha , Khattak Qundeel , Mohamoud Said Aden , Arays Abdullahi , Mohamud Farhan Mohamed , Mohamoud Abdullahi Muse , Mahdi Adan , Omer Meftuh , Mahat Mohamed Billow , Loddo Fabrizio , Tripaldi Marina , Akseer Nadia 
Published: February 2025

AbstractBackgroundAcute malnutrition, also known as wasting, affected an estimated 45 million children under 5 (CU5) globally in 2023. Wasting is measured using a child’s mid upper arm circumference (MUAC), weight-for-height z-score (WHZ), or nutritional edema. In low-resource contexts, MUAC is often the only measurement used to regularly screen for malnutrition, but recent research suggests MUAC alone fails to diagnose 25%-80% of WHZ-wasted children. MUACZ, an age-adjusted MUAC z-score, may identify additional cases missed by MUAC alone.MethodsThis was a secondary analysis of 1,408 CU5 enrolled in a cluster-randomized controlled trial in two high-wasting regions of Somalia. This analysis explored wasting prevalences, concordance between indicator pairs, linear regression modelling, and ROC analysis using WHZ as a gold standard to examine alternative MUAC and MUACZ thresholds.ResultsWasting prevalence was 1.5% by MUAC, 8.5% by MUACZ, and 14.8% by WHZ. MUAC alone failed to identify 94% of WHZ-wasted children. There was slight concordance between MUAC and WHZ (κ=0.089) and fair concordance between MUACZ and WHZ (κ=0.385). Linear regression indicated that MUAC, age, sex, and stunting were all statistically significant variables for estimating child WHZ. Using WHZ as a gold standard, a MUAC of 13.7cm and MUACZ of –0.9 SD both accurately diagnosed >82% of wasted children ages 9-23 months. A MUAC of 14.4cm and MUACZ of −1 SD both accurately diagnosed >76% of wasted children ages 24-59 months.ConclusionPoor concordance between MUAC and WHZ should prompt review of wasting measurement guidelines for this population. Stratified analyses and regression modelling showed increased MUAC with age among CU5. MUACZ or age-specific MUAC thresholds may identify more truly wasted children, improving coverage of treatment interventions. Policymakers should examine how adapting screening guidelines impacts health facilities and treatment availability. Future studies should consider long-term outcomes and mortality associated with increased thresholds of MUAC and MUACZ.RegistrationThe cluster-RCT is registered at ClinicalTrials.gov, ID:NCT06642012.
Oropouche virus importation in Southern Brazil and emerging concern calling for enhanced public health surveillance
Authors: dos Santos Franciellen Machado , de Melo Elverson Soares , de Lima Gustavo Barbosa , da Silva Alexandre Freitas , Santos Paiva Marcelo Henrique , Acioli-Santos Bartolomeu , Lins de Moraes Clarice Neuenschwander , Ruivo Amanda Pellenz , Gregianini Tatiana Schäffer , Bauermann Milena , Bermann Thales , Lagranha Valeska Lizzi , Baethgen Ludmila Fiorenzano , Godinho Fernanda , da Luz Wallau Gabriel , Gorini da Veiga Ana Beatriz , Salvato Richard Steiner 
Published: February 2025

AbstractOropouche virus, an arthropod-borne virus transmitted byCulicoides paraensis, is an endemic arbovirus that mostly circulates in the Amazon basin. However, between 2022 and 2024, it reemerged as a more widespread public health concern in South America. We conducted a pooled-sample molecular surveillance to understand the true prevalence of Oropouche fever in Brazil’s southernmost state. Over 18 months, we analyzed 4,060 samples to monitor the virus emergence in the Rio Grande do Sul state. We detected the first human case of Oropouche virus in the state, and our phylogenetic reconstruction indicated a travel-related introduction from Amazon region into Rio Grande do Sul. Despite the absence of local transmission, the invasion ofCulicoides paraensisand enzootic circulation of the Oropouche virus in Rio Grande do Sul highlight the risk of Oropouche fever outbreaks in the region. We demonstrated that pooled-sample surveillance effectively monitors virus introduction during periods of low endemic circulation, serving as an essential active surveillance tool for the timely detection of virus emergence and enhancing public health preparedness. The multiple introductions of distinct Oropouche virus lineages into southern Brazil underscore the importance of genomic surveillance and public health strategies to monitor and mitigate arbovirus spread in the region.
Novel Digital Gastric Alimetry® Symptom Scales for Use in Gastroduodenal Disorders and Validation against Rome IV Criteria
Authors: Gharibans Armen A. , Huang I-Hsuan , Varghese Chris , Schamberg Gabriel , Taherian Sarvnaz , Dachs Nicky , Law Mikaela , Calder Stefan , Andrews Christopher N. , Tack Jan , O’Grady Greg 
Published: February 2025

AbstractBackgroundPatients with chronic gastroduodenal disorders present with overlapping symptoms. Guidelines emphasize symptom-based criteria, but clinical evaluations are inconsistent due to non-standardized assessments and recall bias. Gastric Alimetry® is a non-invasive test of gastric function enabling real-time symptom evaluation via a standardized app.MethodsParticipants meeting Rome IV criteria for functional dyspepsia (FD) and/or chronic nausea and vomiting syndrome (CNVS) underwent a Gastric Alimetry test, including a meal challenge, with symptoms recorded every 15 minutes in the app. Based on time-of-test symptoms, four novel scores were developed: nausea/vomiting, postprandial distress, epigastric pain, and burning/reflux. Group differences were analyzed using pairwise t-tests, and Rome IV classifications were predicted via logistic regression. Remote moderated usability testing assessed score acceptability.Key ResultsAmong 109 participants (79% female, 18-80 yrs), 54 met criteria for CNVS with/without FD, 41 for postprandial distress syndrome (PDS) only, and 14 for epigastric pain syndrome (EPS) with/without PDS. Symptom scores aligned with Rome IV classifications (p<.05 for CNVS and EPS). Logistic regression showed good discrimination for CNVS (AUC=0.85) and EPS (AUC=0.80), and moderate discrimination for PDS (AUC=0.68). Usability testing confirmed clinical utility and ease of use.Conclusions & InferencesGastric Alimetry symptom scores align with Rome IV classifications, with real-time patient-reported snapshots accurately reflecting chronic symptom burden. These scores provide a clinically applicable diagnostic tool alongside simultaneous physiological gastric function assessments.Key PointsFour novel Gastric Alimetry symptom scores summarize the relative severity of symptoms in subgroups aligned with Rome IV classifications.The proposed time-of-test symptom scores showed moderate-to-good ability to predict diagnoses made using the Rome IV criteria.Usability testing with eight clinicians showed that the scores provided an easy-to-use and clinically useful tool to complement diagnosis of gastroduodenal disorders.
SBDH-Reader: an LLM-powered method for extracting social and behavioral determinants of health from medical notes
Authors: Gu Zifan , He Lesi , Naeem Awais , Chan Pui Man , Mohamed Asim , Khalil Hafsa , Guo Yujia , Shi Wenqi , Dupre Matthew E. , Xiao Guanghua , Peterson Eric D. , Xie Yang , Navar Ann Marie , Yang Donghan M. 
Published: February 2025

ABSTRACTIntroductionSocial and behavioral determinants of health (SBDH) are increasingly recognized as essential for prognostication and informing targeted interventions. While medical notes contain rich SBDH details, these are unstructured and conventional extraction methods tend to be labor intensive, inaccurate, and/or unscalable. The emergence of large language models (LLMs) presents an opportunity to develop more effective approaches for extracting SBDH data.Materials and MethodsWe developed the SBDH-Reader, an LLM-powered method to extract structured SBDH data from full-length medical notes through prompt engineering. Six SBDH categories were queried including: employment, housing, marital relationship, and substance use including alcohol, tobacco, and drug use. The development dataset included 7,225 notes from 6,382 patients in the MIMIC-III database. The method was then independently tested on 971 notes from 437 patients at UT Southwestern Medical Center (UTSW). We evaluated SBDH-Reader’s performance using precision, recall, F1, and confusion matrix.ResultsWhen tested on the UTSW validation set, the GPT-4o-based SBDH-Reader achieved a macro-average F1 ranging from 0.85 to 0.98 across six SBDH categories. For clinically relevant adverse attributes, F1 ranged from 0.94 (employment) to 0.99 (tobacco use). When extracting any adverse attributes across all SBDH categories, the SBDH-Reader achieved an F1 of 0.96, recall of 0.97, and precision of 0.96 in this independent validation set.ConclusionA general-purpose LLM can accurately extract structured SBDH data through effective prompt engineering. The SBDH-Reader has the potential to serve as a scalable and effective method for collecting real-time, patient-level SBDH data to support clinical research and care.
Distinct cis-acting elements mediate co-localization of mRNAs encoding for co-translational interactors in cytoplasmic clusters
Authors: Shade Qamar , Estrada Marianna , Kramer Guenter , Bukau Bernd , Shiber Ayala 
Published: February 2025

AbstractMany newly synthesized proteins assemble co-translationally, providing a vital mechanism to prevent subunit misfolding in the crowded cytoplasm. Initial evidence indicates that the spatial organization of mRNAs aids this assembly, but it is unclear how these mRNAs are organized and how common this mechanism is. We used single-molecule Fluorescence in situ Hybridization to examine the spatial organization of mRNAs encoding subunits of various cytosolic complexes involved in critical cellular functions, such as fatty acid synthesis, glycolysis, translation and amino acid biosynthesis. We found that mRNAs of the same protein complex often co-localize in specific cytoplasmic clusters. Additionally, we observed that the mRNAs encoding enzymes of biosynthetic pathways are organized in cytosolic clusters. Focusing on mRNAs encoding fatty acid synthase complex subunits, we discovered that non-coding cis-elements significantly influence mRNA localization in an additive manner. Inhibiting mRNA co-localization impaired growth when complex activity was essential, highlighting the importance of mRNA spatial organization for cellular survival. Transiently disrupting mRNA translation also affected clustering, indicating that both the nascent chains and mRNA sequence targeting cues are important for spatial organization. In summary, we provide evidence that mRNA co-localization in cytoplasmic foci is coordinated by complementary mechanisms crucial for co-translational assembly, allowing efficient regulation of protein complex formation and entire pathways.