bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the effect of social contact structure on the impact of pneumococcal conjugate vaccines
Authors: Wong Anabelle , Kramer Sarah C. , Weinberger Daniel M. , de Cellès Matthieu Domenech 
Published: August 2024

AbstractAlthough pneumococcal conjugate vaccines (PCVs) have greatly reduced diseases caused by vaccine-targeted serotypes (VT) ofStreptococcus pneumoniae, vaccine impact may be eroded by the increase in rates of disease caused by non-vaccine serotypes (NVT). Here, we investigated the effect of social contact patterns on the dynamics of vaccine impact in carriage.We developed a neutral, age-structured, Susceptible–Colonized model incorporating VT-NVT co-colonization and verified it against real-world carriage data in children. Using contact matrices from 34 countries, we assessed the impact of contact patterns on the time required to eliminate VT (i.e., 95% reduction in VT proportion in carriage). Finally, we quantified the contribution of various parameters—such as vaccine efficacy, coverage, immunity waning, and population susceptibility—to the dynamics of VT elimination.Our model recapitulated the observed decline of VT carriage and showed that varying the contact structure alone led to different time-to-elimination. We found that higher total contact rate and assortativity in children under 5 accelerated VT elimination. Additionally, higher vaccine efficacy and coverage, and slower immunity waning led to shorter time-to-elimination.These findings illuminate the mechanisms controlling the dynamics of vaccine impact and may help predict the impact of PCVs in communities with different contact patterns.
Primary care transformation in Scotland: a comparison two cross-sectional national surveys of general practitioners’ views in 2018 and 2023
Authors: Donaghy E , Sweeney KD , Lauren Ng , Haines Holly , Thompson Alexandra , Henderson D , Wang HHX , Thompson A , Guthrie B , Mercer SW 
Published: August 2024

AbstractObjectivesThe new general practitioner (GP) contract for Scotland, introduced in 2018, established GP Clusters and expanded multidisciplinary team (MDT) working. This paper compares the views of GPs in Scotland regarding the new contract, their working lives, and career intentions in 2018 and 2023.MethodsCross-sectional postal survey of all qualified GPs in Scotland in late 2023 exploring views on Cluster working, MDT-expansion, their working lives, and career intentions, compared with a similar survey from 2018.ResultsJob pressure was significantly higher in 2023 than 2018, but overall job satisfaction and negative job attributes were unchanged, while positive job attributes improved. More GPs were planning to reduce their hours and leave direct patient care in 2023 than 2018.Quality leads views on Cluster working were unchanged, with 70-80% reporting insufficient support in both surveys. Cluster knowledge and engagement was unchanged but all GPs showed small but significant increases in understanding of quality improvement. Most felt MDT expansion was insufficient to reduce workload and fewer GPs reported giving longer consultations for complex patients in 2023 than 2018. Significantly more practices were trying to recruit GPs in 2023, and GPs reported worsening NHS services, higher workload, and lower practice sustainability. Only 1 in 20 GPs in the 2023 survey thought that the new contract had improved the care of patients with multimorbidity.ConclusionsGPs report few improvements in working life five years after the new contract was introduced, and are responding by planning to reduce their hours or leave direct patient care.
Local genetic covariance analysis with lipid traits identifies novel loci for early-onset Alzheimer’s Disease
Authors: Ray Nicholas R. , Bradley Joseph , Yilmaz Elanur , Kizil Caghan , Kurup Jiji T. , Martin Eden R. , Klein Hans-Ulrich , Kunkle Brian W. , Bennett David A. , de Jager Philip L. ,   Alzheimer’s Disease Genetics Consortium, Beecham Gary W. , Cruchaga Carlos , Reitz Christiane 
Published: August 2024

ABSTRACTBackgroundThe genetic component of early-onset Alzheimer’s disease (EOAD), accounting for ∼10% of all Alzheimer’s disease (AD) cases, is largely unexplained. Recent studies suggest that EOAD may be enriched for variants acting in the lipid pathway.ObjectiveTo examine the shared genetic heritability between EOAD and the lipid pathway by genome-wide multi-trait genetic covariance analyses.MethodsSummary statistics were obtained from the GWAS meta-analyses of EOAD by the Alzheimer’s Disease Genetics Consortium (n=19,668) and five blood lipid traits by the Global Lipids Genetics Consortium (n=1,320,016), and genetic covariance analyses were performed via SUPERGNOVA. Genes in linkage disequilibrium (LD) with top EOAD hits in identified regions of covariance with lipid traits were scored and ranked for causality by combining evidence from gene-based analysis, AD-risk scores incorporating transcriptomic and proteomic evidence, eQTL data, eQTL colocalization analyses, DNA methylation data, and single-cell RNA sequencing analyses.ResultsLocal genetic covariance analyses identified 3 regions of covariance between EOAD and at least one lipid trait. Gene prioritization nominated 3 likely causative genes at these loci:ANKDD1B,CUZD1, andMS4A64.ConclusionThe current study identified genetic covariance between EOAD and lipids, providing further evidence of shared genetic architecture and mechanistic pathways between the two traits.
Paramagnetic Rim Lesions are Highly Specific for Multiple Sclerosis in Real-World Data
Authors: Hemond Christopher C. , Dundamadappa Sathish K. , Deshpande Mugdha , Baek Jonggyu , Brown Robert H. , Ionete Carolina , Reich Daniel S. 
Published: August 2024

AbstractBackgroundParamagnetic rim lesions (PRL) are an emerging biomarker for multiple sclerosis (MS). In addition to associating with greater disease severity, PRL may be diagnostically supportive.ObjectiveOur aim was to determine PRL specificity and sensitivity for discriminating MS from its diagnostic mimics using real-world clinical diagnostic and imaging data.MethodsThis is a retrospective, cross-sectional analysis of a longitudinal cohort of patients with prospectively collected observational data. Patients were included if they underwent neuroimmunological evaluation in our academic MS center, and had an available MRI scan from the same clinical 3T magnet that included a T2*-weighted sequence with susceptibility postprocessing (SWAN protocol, GE). SWAN-derived filtered phase maps and corresponding T2-FLAIR images were manually reviewed to determine PRL. PRL were categorized as “definite,” “probable,” or “possible” based on modified, recent consensus criteria. We hypothesized that PRL would convey a high specificity to discriminate MS from its MRI mimics.Results580 patients were evaluated in total: 473 with MS, 57 with non-inflammatory neurological disease (NIND), and 50 with other inflammatory neurological disease (OIND). Identification of “definite” or “probable” PRL provided a specificity of 98% to discriminate MS from NIND and OIND; sensitivity was 36%. Interrater agreement was almost perfect for definite/probable identification at a subject level.ConclusionsPRL convey high specificity for MS and can aid in the diagnostic evaluation. Modest sensitivity limits their use as single diagnostic indicators. Including lesions with lower confidence (“possible” PRL) rapidly erodes specificity and should be interpreted with caution given the potential harms associated with misdiagnosis.
Age at Menarche and Coronary Artery Disease Risk: Divergent Associations with Different Sources of Variation
Authors: Sonawalla Ambreen , Chasman Daniel I. , Chan Yee-Ming 
Published: August 2024

AbstractBackgroundIn women, both earlier and later age at menarche (AAM) are associated with increased risk of coronary artery disease (CAD). This study sought to determine if the relationship of AAM with CAD and CAD risk factors differs for different underlying sources of variation in AAM – specifically, variation attributable to common genetic variants as represented by a polygenic score (PGS) vs. variation in AAM adjusted for the PGS.MethodsPrimary analyses were conducted on data from 201,037 women in the UK Biobank and validation studies on data from 23,268 women in the Women’s Genome Health Study (WGHS). For each individual, a PGS for AAM was calculated, then two variables were estimated from linear regression models: the genetically predicted AAM (the estimated AAM for each woman solely due to the effects of common genetic variants) and the PGS-adjusted AAM (estimated AAM for each woman solely due to factors other than the PGS). Logistic regression and linear splines were then used to study the relationships of these variables with CAD and CAD risk factors.ResultsGenetically predicted AAM demonstrated a linear relationship with CAD and linear or roughly linear relationships with CAD risk factors. In contrast, PGS-adjusted AAM demonstrated a U-shaped relationship with CAD and with hemoglobin A1c, triglycerides, HDL-C, and waist-hip ratio. Validation studies using WGHS data produced similar results.ConclusionsThese results suggest that later AAM itself does not cause increased risk of CAD; rather, upstream sources of variation other than common genetic variants can cause both later AAM and increased risk of CAD. Dysglycemia, dyslipidemia, and central adiposity are candidate mediators of the association of later AAM with increased risk of CAD.
Within-visit Blood Pressure Variability in Children and Adolescents in the National Health and Nutrition Examination Survey (2013-2020)
Authors: Riar Sandeep K , Gillespie Scott , South Andrew M 
Published: August 2024

AbstractBackgroundIt is assumed that BP decreases with repeat measurements and multiple readings are recommended. There is limited information about within-visit BP variability (BPV) in healthy children.MethodsWe used NHANES data (2013-2020) to measure BPV in subjects 8-17 years old with three BP readings. During 2013 to 2016, auscultatory BP was obtained (manual protocol, MP). Subsequently, oscillometric BP was measured (automated protocol, AP). We excluded subjects with diastolic BP ‘zero’.ResultsWe included a total 5656 subjects with 3365 (59.5%) in the MP and 2291 (40.5%) in the AP group. A ΔBP (individual-level difference between the highest and lowest of three BP readings) ≥5 mmHg was noted in 49.1% and 60.7% subjects for systolic BP (SBP) and diastolic BP (DBP) respectively. A ΔDBP ≥10 mmHg and DBP average real variability ≥10 mmHg was twice as common in the MP than AP group. A ΔBP ≥20 mmHg was noted in 1.3% and 4.4% subjects for SBP and DBP respectively. The first SBP and DBP reading was ≥5 mmHg higher or lower than the averaged second and third SBP and DBP readings in 24.9% and 34.5% of subjects respectively. The first SBP and DBP reading was the highest of three BP readings in 44.2% and 42.4% subjects respectively.ConclusionsThere is significant BPV in children and adolescents. Diastolic BPV is more common in MP than AP groups. Initial BP is not always the highest and inclusion of second and third BP reading may be more representative of patient’s actual BP.
Heparanase 2 regulates endothelial permeability and prevents from proteinuria via VEGFA and FGF signaling
Authors: Becker Yannic , Tkachuk Sergey , Jörns Anne , Alwakaa Ahmad , Hegermann Jan , Schenk Heiko , Kiyan Yulia , Haller Hermann 
Published: August 2024

AbstractBackgroundHeparan sulfates (HS) attached to the apical surface of vascular endothelial cells (ECs) play an important role in regulating endothelial permeability and ligand recognition by cell-surface receptors. Shedding of heparan sulfate (HS) from the EC surface increases vascular leakage and is associated with vascular diseases. Recently, heparanase 2 (Hpa2) was described as a novel regulatory molecule that controls HS shedding. However, its role in regulating HS physiology in the vascular endothelium is largely unknown. Here, we characterize the role of endogenous Hpa2 in the vertebrate vascular system.MethodsWe use zebrafish larvae as our primary animal model. Hpa2 expression and localization was examined byin situhybridization and immunofluorescence. Hpa2 loss-of-function (LOF) was induced by CRISPR-Cas9 or morpholino antisense strategies. We assessed vascular permeability, blood vessel architecture, and EC morphology using transgenic zebrafish and transmission electron microscopy. EC expression profiles and HS quantity were analyzed in Hpa2-LOF larvae. The capacity of recombinant Hpa2 to modulate signaling in ECs by the HS-binding growth factors fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A165(VEGFA165) was tested by western blotting and immunofluorescence. Attenuation of the Hpa2-LOF phenotype was testedin vivoin zebrafish larvae via use of recombinant Hpa2 and pharmacological inhibition of FGF and VEGFA signaling.ResultsWe detectedhpse2expression in hepatic tissue and localized the protein in blood vessels. Hpa2-LOF larvae exhibited increased vascular permeability, occasional hypersprouting, and altered EC and extracellular matrix (ECM) morphology. Hpa2-LOF also reduced HS levels and caused changes in the endothelial transcriptome characterized by dysregulated genes involved in ECM-receptor interaction and signal transduction regulation. Recombinant hHpa2 rescued the Hpa2-LOF phenotype in zebrafish. We showedin vitrothat Hpa2 competes with FGF2 and VEGFA165for binding on the EC surface and consequently reduces the cellular response these factors elicit. Pharmacological inhibition of these pathways alleviated the Hpa2-LOF phenotype in zebrafish.ConclusionWe conclude that Hpa2 is a circulating molecule that maintains vascular integrity by regulating HS-dependent processes on the EC surface. These results may translate into novel strategies applying recombinant Hpa2 to treat microvascular diseases.
Global genomic surveillance of monkeypox virus
Authors: Otieno James R. , Ruis Christopher , Onoja Bernard A. , Kuppalli Krutika , Hoxha Ana , Nitsche Andreas , Brinkmann Annika , Michel Janine , Mbala-Kisengeni Placide , Mukadi-Bamuleka Daniel , Osman Muntasir Mohammed , Hussein Hanadi Elawad , Raja Muhammad Ali , Fotsing Richard , Herring Belinda L. , Keita Mory , Rico Jairo Mendez , Gresh Lionel , Barakat Amal , Katawera Victoria , Nahapetyan Karen , Naidoo Dhamari , Floto R. Andres , Cunningham Jane , Van Kerkhove Maria D. , Lewis Rosamund , Subissi Lorenzo 
Published: August 2024

AbstractMonkeypox virus (MPXV) is endemic in Western and Central Africa and, in May 2022, a clade IIb lineage (B.1) caused a global outbreak outside Africa, resulting in its detection in 117 countries/territories. To understand the global phylogenetics of MPXV, we carried out the first analysis of all available MPXV sequences, including 10,670 sequences from 65 countries collected between 1958 and 2024. Our analysis reveals high mobility of clade I viruses within Central Africa, sustained human-to-human transmission of clade IIb lineage A viruses within the Eastern Mediterranean region, and distinct mutational signatures that can distinguish sustained human-to-human from animal-to-animal transmission. Moreover, distinct clade I sequences from Sudan suggest local MPXV circulation in areas of Eastern Africa over the past four decades. Our study underscores the importance of genomic surveillance in tracking spatiotemporal dynamics of MXPV clades and the need to strengthen such surveillance, including in some parts of Eastern Africa.
Prognostic frailty-based determinants of long-term mortality in older patients with newly diagnosed multiple myeloma
Authors: Muzyka Mariya , Ottaviani Silvia , Caffa Irene , Bonfiglio Tommaso , Parisi Erica , Guijarro Ana , Tagliafico Luca , Lemoli Roberto , Ponzano Marta , Marelli Cristina , Signori Alessio , Nencioni Alessio , Cea Michele , Monacelli Fiammetta 
Published: August 2024

AbstractIntroductionMultiple myeloma (MM) is a plasma cell neoplasm predominantly diagnosed in older adults. However, the significance of defining patient frailty, as well as identifying the most suitable and reliable tools for its assessment, remains to be firmly established.Materials and MethodsThis retrospective observational study investigated 36 patients, aged 65 or older, who underwent Comprehensive Geriatric Assessment (CGA). The average patient age was 76 (SD 6.22), with 33.3% being female. Patients were evaluated using the International Myeloma Working Group Frailty Index (IMWG-FI) and the 40-item Rockwood’s Frailty Index (FI) at the Oncogeriatrics clinic of the IRCCS Polyclinic San Martino Hospital, Genoa, Italy, between December 2017 and August 2021. Laboratory, cancer-specific, demographic, and clinical variables were collected. Survival analysis and frailty comparison were conducted using Stata version 17.0.ResultsStepwise multivariate analysis identified Numerical Rating Scale (NRS) (HR 1.40, 95% CI 1.09-1.78, p=0.008) and Rockwood’s Frailty Index (FI) (HR 2.23, 95% CI 1.29-3.87, p=0.004) as significant prognostic predictors, adjusted for sex, ISS stage, and multimorbility. Comparison between Rockwood’s FI and IMWG-FI using Spearman correlation coefficient showed no statistically significant correlation (r=0.268, p=0.114). Multivariate Cox model, adjusting for sex, International Staging System (ISS) stage, and Cumulative Illness Rating Scale (CIRS) comorbidity index, demonstrated the superior predictive ability of Rockwood’s FI over IMWG-FI (C-index 0.775 vs 0.749).Discussionthe 40-item Rockwood FI emerges as a valuable tool for prognostication in old MM patients, surpassing the traditional IMWG-FI in predictive accuracy, emphasizing the importance of a comprehensive approach considering both disease-specific and patient-related factors.
Emergency Care in India: A Retrospective Cross-sectional Analysis of Health Management and Information System and Global Burden of Disease
Authors: Urs Gaurav , Zadey Siddhesh , Kumar Padmavathy Krishna , Gangane Tejali , Nimkar Pushkar , Staton Catherine , Vissoci Joao Ricardo Nickenig 
Published: August 2024

ABSTRACTBackgroundTo understand the utilization and burden of emergency medical conditions (EMCs), we assessed EM Department (EMD) data from the Health Management and Information System (HMIS) of India and EMC from the Global Burden of Diseases (GBD).MethodsThis was a retrospective cross-sectional analysis of HMIS and GBD data for 2019. We extracted EMD registrations, admissions, and deaths from HMIS and incidence, deaths, and DALYs from GBD for 31 EMCs at the national and state levels. We analyzed HMIS and GBD data for proportions and rates of registrations, deaths, and incident cases relative to population counts and hospital admission numbers.ResultsIn 2019, 119,103,358 patients (8,935.66 per 100,000 people) were registered at EMDs. The national EMD registration rate was 6,744.21 per 100,000 hospital admissions and the EMD death rate was 43,939.49 per 100,000 inpatient deaths. Only 12.14% of all HMIS registrations had cause-specific data. GBD estimated 2,047,175,737 EMC incident cases nationally, accounting for 27.22% of all-cause incidence, 51.71% of all-cause mortality, and 42.30% of all-cause DALYs. Trauma-related registrations were 9.27% in HMIS while injuries in GBD accounted for 7% of EMCs. Overall, HMIS EMD registrations were lower than GBD EMC incidence numbers, with regional variations.ConclusionsThe study reveals gaps in the EMD utilization as per HMIS data compared to the EMC burden estimates from GBD. Improved data integration and reporting can address regional disparities.
Simultaneous Heart and Kidney Transplantation utilizing Circulatory Death Donors in the United States
Authors: Tavolacci Sooyun C. , Okumura Kenji , Isath Ameesh , Rodriguez Gabriel B. , De La Pena Corazon , Shimamura Junichi , Lansman Steven L. , Ohira Suguru 
Published: August 2024

AbstractObjectiveHeart transplants utilizing donors from circulatory death (DCD) allografts are rapidly growing with the potential to expand the donor pool. However, little is known about the use of DCD donors for simultaneous heart and kidney transplants (SHKT) compared to SHKT using brain death donors (DBD).MethodsFrom May 22, 2020, to September 30, 2023, 1,129 adult patients received SHKT (DCD, N=91 vs. DBD, N=1,038), identified using the United Network for Organ Sharing database, excluding other multi-organ transplants and re-transplants. A 1:3 ratio propensity score matching was performed using 17 recipient characteristics and 7 donor characteristics. A total of 91 DCD and 273 DBD matched cases were compared.ResultsIn the unmatched cohort, DCD recipients were older (DCD: 60 vs. DBD: 58 years, p=0.03) and had a lower rate of dialysis at transplant (27% vs. 40%, p=0.03) and status 1 to 2 patients (43% vs. 72%, p<.001). Donors were younger (30 vs. 32 years, p=0.02) in the DCD group. In the matched cohort, kidney delayed graft function (27% vs. 22%, p=0.29) was comparable, as were recipient survival (p=0.19), heart graft survival (p=0.19), and kidney graft survival (p=0.17). In multivariate Cox proportional hazards analysis, donor type (DCD) was not associated with an increased risk of mortality (HR=1.69, 95% Cl 0.90-3.16, p=0.10). Sub-group analysis showed that survival and freedom from graft failures were comparable between different modes of DCD recovery. The centers performing both DCD- and DBD-SHKT showed significantly shorter waitlist days with comparable transplant outcomes compared to centers that only performed DBD-SHKT.ConclusionsSHKT using DCD donors yields comparable survival and graft outcomes to those using DBD donors. These findings will guide treatment strategies for heart transplant candidates with kidney dysfunction, including the selection of donors and patients and safety net policy options.
Normalization of Single-cell RNA-seq Data Using Partial Least Squares with Adaptive Fuzzy Weight
Authors: Singh Vikas , Kirtipal Nikhil , Lim Songwon , Lee Sunjae 
Published: August 2024

AbstractNormalization of single-cell RNA-seq (scRNA-seq) is a crucial step in downstream analysis, where raw data are adjusted to correct unwanted factors that prevent the direct comparison of expression measures. scRNA-seq data exhibits a multivariate relationship between transcript-specific expression and sequencing depth that a single scale factor cannot address. A partial least squares (PLS) regression was performed to accommodate the variability of gene expression in each condition, and upper and lower quantiles with adaptive fuzzy weights were utilized to correct unwanted biases in scRNA-seq data. The present approach was compared using real and simulated datasets across various state-of-the-art performance measures.