bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Non-Contrast Enhanced Imaging Input Sequences on the Generation of Virtual Contrast-Enhanced Breast MRI Scans using Neural Networks
Authors: Liebert Andrzej , Schreiter Hannes , Kapsner Lorenz A , Eberle Jessica , Ehring Chris , Hadler Dominique , Brock Luise , Erber Ramona , Emons Julius , Laun Frederik B. , Uder Michael , Wenkel Evelyn , Ohlmeyer Sabine , Bickelhaupt Sebastian 
Published: May 2024

ABSTRACTBackgroundVirtual contrast-enhanced (vCE) imaging techniques are an emerging topic of research in breast MRI.PurposeTo investigate how different combinations of T1-weighted (T1w), T2-weighted (T2w), and diffusion-weighted imaging (DWI) impact the performance of vCE breast MRI.Materials and MethodsThe IRB-approved, retrospective study included 1064 multiparametric breast MRI scans (age:52±12 years) obtained from 2017-2020 (single site, two 3T MRI). Eleven independent neural networks were trained to derive vCE images from varying input combinations of T1w, T2w, and multi-b-value DWI sequences (b-value=50–1500s/mm2). Three readers evaluated the vCE images with regards to qualitative scores of diagnostic image quality, image sharpness, satisfaction with contrast/signal-to-noise-ratio, and lesion/non-mass enhancement conspicuity. Quantitative metrics (SSIM, PSNR, NRMSE, and median symmetrical accuracy) were analyzed and statistically compared between the input combinations for the full breast volume and both enhancing and non-enhancing target findings.ResultsThe independent test set consisted of 187 cases. The quantitative metrics significantly improved in target findings when multi-b-value DWI sequences were included during vCE training (p<.05). Non-significant effects (p>.05) were observed for the quantitative metrics on the full breast volume when comparing input combinations including T1w. Using T1w and DWI acquisitions during vCE training is necessary to achieve high satisfaction with contrast/SNR and good conspicuity of the enhancing findings. The input combination of T1w, T2w, and DWI sequences with three b-values showed the best qualitative performance.ConclusionvCE breast MRI performance is significantly influenced by input sequences. Quantitative metrics and visual quality of vCE images significantly benefit when a multi b-value DWI is added to morphologic T1w-/T2w-sequences as input for model training.Key ResultsThe inclusion of diffusion-weighted imaging significantly improves the conspicuity of lesions/non-mass enhancements and satisfaction with the image contrast in virtual contrast-enhanced breast MRI.The quality of virtual contrast-enhanced breast MRI scans benefits from the inclusion of high-resolution morphologic T1-weighted image acquisitions.Quantitative metrics such as the structural similarity index and peak signal-to-noise ratio calculated over the entire breast volume insufficiently reflect variations in lesion/non-mass enhancement’s individual characteristics.
Barriers to sexual and reproductive health and rights of migrant and refugee youth: An exploratory socio-ecological qualitative analysis
Authors: Aibangbee Michaels , Micheal Sowbhagya , Liamputtong Pranee , Pithavadian Rashmi , Hossain Syeda Zakia , Mpofu Elias , Dune Tinashe 
Published: May 2024

AbstractPurposeMigrants and refugee youths’ (MRY) sexual and reproductive health and rights (SRHR) is a global health issue. MRY tend to encounter adverse SRH experiences because of their limited access to and knowledge of SRHR services. Using a socioecological framework, this study examined the barriers affecting MRY’s SRHR.MethodsA cross-sectional study utilising a participatory action research design was used. 87 MRY (ages 16-26, from 20 different cultural groups living in Greater Western Sydney, Australia) participated in the study and completed seventeen focus group discussions on MRY’s experiences of SRHR. Focus groups were co-facilitated by youth project liaisons for authenticity and validity. The data were analysed thematically and interpreted using socioecological theory.ResultsThe findings identified socioecological barriers such as lack of awareness and access to services, sociocultural dissonance, and under-implementation of SRHR services. These barriers include cultural disconnects, language barriers, remote service locations, intergenerational cultural conflicts, and ineffective SRHR services. Key themes included traditional and institutional stigma, lack of SRH education, reliance on social media for SRH information and privacy concerns.ConclusionThere is limited consideration of MRY’s SRHR and the impact of intergenerational discordance and stigma on MRY’s rights. The findings suggest the necessity for a collaborative SRHR strategy and policy design that empowers MRY’s agency across multicultural contexts.
In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson’s
Authors: Cortés Adriana , Phung Toan K. , de Mena Lorena , Garrido Alicia , Infante Jon , Ruíz-Martínez Javier , Galmés-Ordinas Miquel À. , Glendinning Sophie , Pérez Jesica , Roig Ana , Soto Marta , Cosgaya Marina , Ravasi Valeria , Fernández Manel , Rubiano-Castro Alejandro , Díaz Ramón , Hernández-Eguiazu Haizea , Sánchez-Quintana Coro , Vinagre-Aragón Ana , Mondragón Elisabet , Croitoru Ioana , Rivera-Sánchez María , Corrales-Pardo Andrea , Sierra María , Tolosa Eduardo , Malagelada Cristina , Nirujogi Raja S. , Fernández-Irigoyen Joaquín , Santamaría Enrique , Alessi Dario R. , Martí María J. , Ezquerra Mario , Fernández-Santiago Rubén 
Published: May 2024

ABSTRACTLeucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson’s disease (L2PD) and idiopathic PD (iPD). Yet, pharmaco-dynamic readouts and progression biomarkers for disease modification clinical trials are insufficient. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174) encompassing G2019S L2PD patients (n=37), non-manifesting LRRK2 mutation carriers of G2019S, here, G2019S L2NMCs (n=27), R1441G L2PD patients (n=14), R1441G L2NMCs (n=11), iPD (n=40), and controls (n=45). We identified 207 differential proteins in G2019S L2PD compared to controls (39 up/ 168 down) and 67 in G2019S L2NMCs (10 up/ 57 down). G2019S down-regulated proteins affected the endolysosomal pathway, proteostasis and mitochondria, e.g., ATIC, RAB9A, or LAMP1. At the phospho-proteome level, we observed increases in endogenous phosphorylation levels of pSer106 RAB12 in G2019S carriers, which were validated by immunoblotting after 1 year of follow-up (n=48). Freshly collected PBMCs from 3 G2019S L2PD, 1 R1441G L2PD, 1 iPD, and 5 controls (n=10) showed strong diminishment of pSer106 RAB12 phosphorylation levels after in-vitro administration of the MLi-2 LRRK2 inhibitor. Using machine learning, we identified an 18-feature G2019S phospho-/protein signature capable of discriminating G2019S L2PD, L2NMCs, and controls with 96% accuracy that correlated with disease severity, i.e., UPDRS-III motor scoring. Our study identified pSer106 RAB12 as an endogenous biomarker in easily accessible PBMCs from G2019S carriers and suggests that phospho-/proteomic findings in human PBMCs such as pSer106 RAB12 can be deployed as a universal pharmaco-dynamic readout for L2PD, L2NMCs, and iPD. Future work may determine whether pSer106 RAB12 could help with patient enrichment and monitoring drug efficacy in LRRK2 clinical trials.
Sensitive detection of copy number alterations in samples with low circulating tumor DNA fraction
Authors: Mayrhofer Markus , Bergström Rebecka , Chellappa Venkatesh , Kotsalaynen Anastassija , Murugan Sarath , Crippa Alessio , De Laere Bram , Urtishak Karen , Sorensen Karina Dalsgaard , Garg Kavita , Singh Usha , Eklund Martin , Grönberg Henrik , Lindberg Johan 
Published: May 2024

AbstractCopy number analysis is an important aspect of cancer genomics that enables identification of activated oncogenes, inactivated tumor suppressor genes and genome-wide signatures such as homologous recombination deficiency and the tandem duplication phenotype. Despite continuous development of copy number algorithms, the current sensitivity to detect clinically relevant focal alterations is poor if the cancer DNA fraction is low. This is particularly challenging for analysis of circulating tumor DNA (ctDNA) as it is not possible to know the cancer DNA fraction in advance or, as for tissue, macrodissect to increase the cancer DNA fraction. Here, we combine a novel algorithm (Jumble) with a tailored gene panel design and selected reference samples that achieve sensitive and highly specific detection of clinically relevant copy number alterations with limits of detection at 1-2% ctDNA fraction for amplifications and 4-8% for homozygous deletions. Jumble lowers the ctDNA fraction required for detection of homozygous deletions 3-6 times compared to commercial alternatives. Jumble is freely available as an R script and container, ready for integration into bioinformatic pipelines.
A Study of a Stochastic Model and Extinction Phenomenon of Meningitis Epidemic
Authors: Yaga S.J. , Saporu F.W.O. 
Published: May 2024

AbstractA stochastic version of the deterministic model for meningitis epidemic by Yaga and Saporu (2024) is developed. The stochastic mean system of equations for possible state of an individual in the model and the extinction probabilities for carrier and infective are derived. Comparison of the system of stochastic mean equations and its deterministic analogue of profiles for the various compartments and the case-carrier trajectories show similar pattern with a time shift difference. This indicates that there must be caution in using the deterministic analogue as an approximating system of the stochastic mean equations for inferential purpose. Simulation studies of the comparison of the compartmental profiles for the general case; model I, with the assumption that a proportion (φ ≠0), of the infected susceptible can move directly to the infective stage and that of the special case, model II, whenφ= 0 is examined for various values ofϵ(odds in favour of a carrier transmitting infection)≤2. It is only whenϵ= 2 that model II can approximate model I in all compartments except that of the carrier. Transmission rate,β, loss of carriership rate,σandϵare identified as the most sensitive parameters of the extinction probabilities. Threshold results derived for carrier and infective extinction probabilities are distinct but bear some relation, transmission rate required for carrier extinction is square of that for infective. It is concluded that carriership play a more prominent role in the transmission of meningitis epidemic and efforts aimed at control should be targeted at reducing the transmission rate and increasing the loss of carriership.
Elevated polyreactive immunoglobulin G in immune mediated liver injuries with the need for immunosuppressive therapy
Authors: Kirchner Theresa , Dalekos George N. , Zachou Kalliopi , Robles-Díaz Mercedes , Andrade Raúl J. , Sebode Marcial , Lohse Ansgar , Janik Maciej K. , Milkiewicz Piotr , Kolev Mirjam , Semmo Nasser , Bruns Tony , Gevers Tom Jg , Beretta-Piccoli Benedetta Terziroli , Wedemeyer Heiner , Jaeckel Elmar , Taubert Richard , Engel Bastian ,   pIgG study group
Published: May 2024

AbstractBackground and aimThe distinction of drug-induced liver injury (DILI), drug-induced autoimmune-like hepatitis (DI-ALH) and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker with a higher accuracy for the diagnose of AIH than conventional autoantibodies. This retrospective multicenter study aimed to evaluate the diagnostic accuracy of pIgG to distinguish between AIH, DI-ALH and DILI and thus identify patients in need of immunosuppression.MethodsSamples from 116 patients (AIH=81, DI-ALH=12, DILI=23) were recruited and compared to a control group (non-AIH-non-DILI-LD= 596) from existing biorepositories.ResultsNo patient in the DILI-group but 98% in the AIH-and 92% in the DI-ALH-group received immunosuppressive treatment. pIgG levels were significantly higher in the AIH-group (1.9 normalized arbitrary units (nAU) compared to DILI (1.1 nAU, p<0.001) and non-AIH-non-DILI-LD (1.0 nAU, p<0.001). Median pIgG concentrations of the DI-ALH-group (1.7 nAU) were between AIH (p=.634) and DILI (p=.052). Patients that needed immunosuppressive therapy for remission induction had significantly higher pIgG concentrations compared to those with spontaneous recovery of liver injury (1.8 nAU vs. 1.1 nAU, p<.001). The overall accuracy of pIgG >1.27nAU to distinguish AIH from DILI (74%) and liver injuries with and without the need for immunosuppression (74%) was similar to that of ANA (71/74%) and SMA (74/70%) at cut-offs of ≥1/40.ConclusionPolyreactive IgG can be used to predict AIH in comparison to DILI and indicate the need for immunosuppressive therapy in the work-up of immune mediated or drug-induced liver injuries.
Psychosocial Profiles of Older Adults by Dentition Status and Dental Utilization History
Authors: Finlayson T.L. , Moss K. , Jones J.A. , Preisser J.S. , Weintraub J.A. 
Published: May 2024

ABSTRACTObjectivePsychosocial factors can affect health. Patterns of psychosocial stressors and resources among older adults were examined for oral health status.MethodsThe Health and Retirement Study (HRS) is a representative sample of US adults >50 years. Participants completed the 2018 HRS CORE survey and Psychosocial and Lifestyle Questionnaire–Panel A “Leave Behind” survey (HRS-LB)(N=4703). All measures were self-reported, and stratified into outcome groups: 1) edentulous/dentate, 2) with/without a recent dental visit in the last two years. Psychosocial measures covered three domains: well-being, beliefs, and lifestyle. Specifically, we studied loneliness, life satisfaction, perceived age, social status, control, mastery, and chronic stressors. Latent class analysis (LCA) identified profiles of adults based on the distribution of psychological and social stressors and resources. Associations between latent classes and being edentulous and a recent dental visit were examined in logistic regression models.ResultsAbout 30% reported no recent dental visit; 14% were edentulous. Three latent classes were identified; profiles had different distributions of psychosocial factors. Half were in Class A:“Satisfied/Connected” (n=2230), 27% in Class B:“Satisfied/Lonely” (n=1293), and 25% in Class C:“Unsatisfied/Lonely” (n=1180). “Satisfied/Connected” adults had the fewest psychosocial risk factors, most resources, were dentate, with a recent dental visit. “Unsatisfied/Lonely” adults exhibited the most psychosocial risk factors and fewest resources, more were edentulous and lacked a recent dental visit. “Satisfied/Lonely” adults exhibited characteristics between Classes A and C. In fully adjusted regression models, Class B adults had 1.29 (1.03-1.61) times greater odds than Class A to be edentulous, and 1.27 (1.07-1.50) times greater odds to not have a recent dental visit. Class C adults had 1.20 (0.96-1.51) times greater odds than Class A to be edentulous, and 1.33 (1.11-1.58) times greater odds to not have recent dental visit.ConclusionAdverse psychosocial factors are associated with edentulism and lack routine dental visits.
Usefulness of ecological mobility and socio-economic indicators in SARS-CoV-2 infection modelling: a French case study
Authors: Romain-Scelle Nicolas , Riche Benjamin , Benet Thomas , Rabilloud Muriel 
Published: May 2024

AbstractIntroductionFollowing its emergence in January 2020, SARS-CoV-2 diffusion occurred for a year with only non-pharmaceutical interventions (NPIs) available as mitigation tools. We aimed to assess the predictive capability of census-based indicators on the infection risk by SARS-CoV-2 in the French Auvergne-Rhône-Alpes region to assist NPIs allocation at the neighbourhood level.MethodsWe aggregated all counts of biologically confirmed cases of SARS-CoV-2 infection at the neighbourhood level between May 2020 and February 2021. 10 census-based ecological covariates were evaluated as predictors of case incidence using a Poisson regression with conditional autoregressive (CAR) spatial effects. Benefits of CAR effects and covariates on model fit were evaluated using pseudo-R² and Moran’s I statistics.Results438,992 infection cases over 5,410 neighbourhoods among 7,917,997 inhabitants were analysed. The association between covariates and case incidence was inconstant across time and space. Spatial correlation was estimated at high levels. Spatial CAR effects were necessary to improve on the pseudo-R2and the Moran’s I statistics compared to the null model (intercept only).ConclusionThe ecological covariates assessed were insufficient to adequately model the distribution of cases at the neighbourhood level. Excess incidence was found mainly in metropolitan areas before the epidemic wave peak.
The causal correlation between gastroesophageal reflux disease and chronic widespread pain: a bidirectional mendelian randomization study
Authors: Chen Menglin , Tu Houshu , Zhou Jiaoli , Zhang Yi , Wen Shuting , Xiao Yao , He Ling 
Published: May 2024

AbstractBackgroundPrevious observational research found a relationship between gastroesophageal reflux disease (GERD) and chronic widespread pain (CWP). Despite this, it is unknown which, if any, of the conditions produces the other. Our study will use bidirectional Mendelian randomization (MR) to evaluate their causal link.MethodsWe examined two sets of publically accessible data from genome-wide association studies (GWAS): GERD (129,080 cases and 602,604 controls) and CWP (6,914 cases and 242,929 controls). We used the inverse variance weighting (IVW) approach as the major analysis method, but we also ran weighted median and MR-Egger regression analyses. We performed various sensitivity studies to assess the conclusions’ consistency, horizontal pleiotropy, and stability.ResultsMR analysis showed that CWP increased the risk of developing GERD [NSNP= 4, odds ratio (OR): 245.244; 95% confidence interval (CI): 4.35E+00,1.38E+04; p = 0.007 < 0.05] and vice versa (NSNP= 28; OR:1.019; 95% CI: 1.009-1.029; p = 0.029 < 0.05). Bidirectional evidence of causality existed. The sensitivity analysis demonstrated the robustness and reliability of the findings.ConclusionsOur study demonstrated a bidirectional causal relationship between GERD and chronic widespread pain, and future interventions for CWP may be an effective strategy for preventing or mitigating GERD and vice versa.
Clinical safety and pharmacokinetics of a novel oral niclosamide formulation compared with marketed niclosamide chewing tablets in healthy volunteers: a three-part randomized, double-blind, placebo-controlled trial
Authors: Walther Niklas , Schultz-Heienbrok Robert , Staß Heino , Corman Victor M. , Gassen Nils C. , Müller Marcel A. , Drosten Christian , Witzenrath Martin , Lee Hweeling , Posch Maximilian G. 
Published: May 2024

AbstractAimNiclosamide is an established anthelmintic substance and a promising candidate for treating cancer, viral infections, and other diseases. However, its solubility in aqueous media is low, and the systemic bioavailability of the commercially available chewing tablet is poor, limiting the use of niclosamide for systemic treatment. A liquid oral formulation using polyethylene glycol 400 was developed and investigated in healthy volunteers to assess safety, tolerability, and pharmacokinetics in comparison to the marketed tablet. (ClinicalTrials.gov:NCT04644705)MethodsThe study consisted of three parts: Part A was a double-blind placebo-controlled single ascending dose trial in three dose groups (200, 600, and 1600 mg) with four participants receiving either the investigational niclosamide formulation or placebo (3:1) under fasted and/or fed conditions. Part B was a crossover study comparing 1600 mg investigational niclosamide solution with the marketed 2000 mg chewing tablet in four healthy volunteers. Part C was a double-blind placebo-controlled multiple-dose trial comparing 1200 mg and 1600 mg (verum: placebo 4:2) in two dose groups with six subjects each, who received daily doses for seven days.ResultsNo serious or severe adverse events occurred. The most frequent adverse events were mild to moderate gastrointestinal reactions. There was also no apparent dependence between drug exposure levels (AUC, Cmax) and the severity and incidence of adverse events detectable. A relevant food effect was observed with a mean AUClastabout 2-fold higher in fed condition compared to fasted condition. In Part B, dose-normalized Cmaxand AUClastwere similar for niclosamide solution and tablet. Absorption of niclosamide solution was highly variable. Some individuals showed high absorption (Cmax>2µg/ml) whereas others did absorb only marginally. Importantly, there was no dose linearity in the range of 200 mg – 1600 mg. No signs of relevant systemic drug accumulation after multiple administrations were observed.ConclusionOverall safety and tolerability observed in healthy subjects were benign. This is also true for individual “high absorbers” (Cmax>2µg/ml), encouraging further research into niclosamide as a potential therapeutic agent. Galenic optimization, however, will remain challenging as evident from the observed exposure variability and non-linear PK. Non-linearity, if confirmed by additional data, might make niclosamide more suitable for multi-dose rather than high single dose regimens. The observed food effect should also be considered when further investigating systemic niclosamide exposures.
Musculoskeletal Modeling and Movement Simulation for Structural Hip Disorder Research: A Scoping Review of Methods and Applications
Authors: Harrington Margaret S. , Leo Stefania D. F. Di , Hlady Courtney A. , Burkhart Timothy A. 
Published: May 2024

AbstractMusculoskeletal modeling is a powerful tool to quantify biomechanical factors typically not feasible to measurein vivo,such as hip contact forces and deep muscle activations. The purposes of this review were to summarize current modeling and simulation methods in structural hip disorder research and evaluate model validation practices and study reproducibility. MEDLINE and Web of Science were searched to identify literature relating to the use of musculoskeletal models to investigate structural hip disorders (i.e., involving a bony abnormality of the pelvis, femur, or both). Forty-seven articles were included for analysis. Studies either compared multiple modeling methods or applied a single modeling workflow to answer a research question. Overall, differences in outputs were shown between generic models scaled to participants’ anthropometrics and models with additional patient-specific geometry; however, generic models were most commonly used in application studies. The 11 studies that assessed model validation used qualitative approaches only. There was also wide variability and under-reporting of data collection, data processing, and modeling methods. Common assumptions made in musculoskeletal modeling during the model development, validation, and movement simulations were identified that are important to consider when evaluating the clinical applicability of modeling predictions in patients with structural hip disorders. Differences between generic and patient-specific model outputs exist; however, whether the patient-specific models are more accurate is still unknown. Increased transparency in reporting of data collection, signal processing, and modeling methods is needed to increase study reproducibility and allow for better assessment of modeling results.