bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers to surveillance and control of re-emergence of the Chagas disease vectorTriatoma infestansin Arequipa, Peru
Authors: Tamayo Laura D. , Paz-Soldán Valerie A. , Condori Pino Carlos E. , Malaga Chavez Fernando S. , Levy Michael Z. , Gonçalves Raquel 
Published: November 2024

AbstractVector control is usually designed as a top-down system with minimum capacity to respond to specificities of epidemiological settings at fine scale or to adjust to routine stressors. Here, we investigated barriers in Chagas disease vector surveillance and control systems in Arequipa, Peru. We conducted in-depth interviews and focus groups with key stakeholders (n=32) at different levels of the health system and community, using process maps to illustrate the workflow for passive and active surveillance. We identified barriers at each step of the process, including systemic, operational, financial, and policy limitations. For passive surveillance, barriers in community participation to report infestations were linked to challenges in capturing the vector and bringing it to a health facility or community health worker. Amongst systemic barriers were related to the use of a data system that did not meet the needs for recording and managing data on vector control activities. At the policy level, the establishment of quotas on the number of houses staff needed to inspect ignores important determinants for infestation and lacks an appropriate sampling design. We discuss the impact of the reported barriers to effective conduction of surveillance and control activities and the initiatives and strategies that have been designed and assessed to bridge these gaps in order to collaboratively design a more resilient health system.
External validation of plasma CSF1 as a preoperative prognostic marker in patients with resectable intrahepatic cholangiocarcinoma
Authors: Akiki Antonio , Jacobsson Hanna , Nouairia Ghada , Cornillet Martin , Björkström Niklas K. , Sparrelid Ernesto , Taflin Helena , Jansson Hannes 
Published: November 2024

ABSTRACTBackground & AimsLong-term prognosis after resection for intrahepatic cholangiocarcinoma (iCCA) remains poor and the preoperative risk assessment is difficult. A previous single-center study indicated two immune system-related proteins in plasma, colony stimulating factor 1 (CSF1) and TNF-related apoptosis-inducing ligand (TRAIL), as preoperative prognostic factors in iCCA. This study aimed to externally validate CSF1 and TRAIL as prognostic markers for patients with resectable iCCA.MethodsPreoperative plasma CSF1 and TRAIL concentrations (pg/mL) were determined from prospectively collected biobank samples using multiplex immunoanalysis (Proximity Extension Assay), from patients operated for iCCA at two tertiary referral centers, Karolinska (2010-2020) and Sahlgrenska (2019-2023) university hospitals. The primary outcome was overall survival (OS), analyzed by Kaplan-Meier method and Cox regression. Secondary outcome was disease-free survival (DFS).ResultsSixty-one patients with resection for iCCA were included. CSF1 above median was associated with lymph node metastasis (P=0.03). CSF1 was associated with both OS (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.01-1.05) and DFS (HR 1.02, 95% CI 1.00-1.04). The median OS was eight months for patients with CSF1 values in the upper quartile (≥158 pg/mL), compared to an overall median OS of 47 months. While TRAIL was not significantly associated with OS (P=0.22), values in the lower quartile (≤256 pg/mL) were associated with short DFS (P<0.01). Multivariable analyses confirmed the independent prognostic significance of CSF1. The C-index of CSF1 for OS was 0.70, with excellent calibration for three- and five-year OS.ConclusionPlasma CSF1 was validated as a novel independent, well-calibrated preoperative predictor of poor survival in resectable iCCA, which could assist the preoperative risk assessment. Low plasma TRAIL was associated with early recurrence.Impact and implicationsPatients with intrahepatic cholangiocarcinoma (iCCA) suffer a high risk of recurrence within the first years after curative intent surgery, limiting long-term survival. To identify patients where liver surgery has a low potential for cure, prognostic markers are warranted. In the present study, preoperative plasma CSF1, an immune system-related protein, was validated as a novel, well-calibrated predictor for long-term survival after hepatic resection. Plasma CSF1 could assist the preoperative risk assessment in iCCA.
Health economic model to evaluate the cost-effectiveness of smoking cessation services integrated within lung cancer screening
Authors: Evison Matthew , Naylor Rebecca , Malcolm Robert , Holmes Hayden , Taylor Matthew , Murray Rachael L , Callister Matthew E J , Hopkinson Nicholas S , Agrawal Sanjay , Cheeseman Hazel , Baldwin David R , Merchant Zoe , Goodley Patrick , Alsaaty Alaa , Balata Haval , Crosbie Philip A.J. , Booton Richard 
Published: November 2024

ABSTRACTIntroductionIntegrating smoking cessation support into lung cancer screening can improve abstinence rates. However, healthcare decision makers need evidence of cost effectiveness to understand the cost/benefit of adopting this approach.MethodsTo evaluate the cost-effectiveness of different smoking cessation interventions, and service delivery, we used a Markov model, adapted from previous National Institute for Health and Care Excellence guidelines on smoking cessation. This uses long-term epidemiological data to capture the prevalence of the smoking-related illnesses, where prevalence is estimated based on age, sex, and smoking status. Probabilistic sensitivity analysis was conducted to capture joint parameter uncertainty.ResultsAll smoking cessation interventions appeared cost-effective at a threshold of £20,000 per quality-adjusted life year, compared to no intervention or behavioural support alone. Offering immediate smoking cessation as part of lung cancer screening appointments, compared with usual care (onward referral to stop smoking services) was also estimated to be cost-effective with a net monetary benefit of £2,198 per person, and a saving of between £34 and £79 per person in reduced workplace absenteeism among working age attendees. Estimated healthcare cost savings were more than four times greater in the most deprived quintile compared to the least deprived, alongside a fivefold increase in QALYs accrued.ConclusionsSmoking cessation interventions within lung cancer screening are cost-effective and should be integrated so that treatment is initiated during screening visits. This is likely to reduce overall costs to the health service, and wider integrated care systems, improve quality and length of life, and may lessen health inequalities.Key messagesWhat is already known on this topic?Smoking cessation interventions are known to be cost-effective in general. However, their cost-effectiveness specifically within lung cancer screening programmes, where they are not routinely commissioned, remains to be established.What this study addsThis health economic analysis estimates that offering smoking cessation immediately within a lung cancer screening visits is a cost-effective intervention, with a substantial return on investment for the healthcare service, alongside a reduction in health inequalities and an increase in productivity for the wider economy.How this study might affect research, practice or policyThis economic evaluation will provide those commissioning and planning healthcare services with evidence that supports the case for funding smoking cessation services integrated within lung cancer screening programmes as immediate, opt-out services.
Machine Learning-Driven Correction of Handgrip Strength: A Novel Biomarker for Neurological and Health Outcomes in the UK Biobank
Authors: Nazarzadeh Kimia , Eickhoff Simon B. , Antonopoulos Georgios , Hensel Lukas , Tscherpel Caroline , Komeyer Vera , Raimondo Federico , Müller Veronika , Grefkes Christian , Patil Kaustubh R. 
Published: November 2024

AbstractBackgroundHandgrip strength (HGS) is a significant biomarker for overall health, offering a simple, cost-effective method for assessing muscle function. Lower HGS is linked to higher mortality, functional decline, cognitive impairments, and chronic diseases. Considering the influence of anthropometrics and demographics on HGS, this study aims to develop a corrected HGS score using machine learning (ML) models to enhance its utility in understanding brain health and disease.MethodsUsing UK Biobank data, sex-specific ML models were developed to predict HGS based on three anthropometric variables and age. A novel biomarker, ΔHGS, was introduced as the difference between true HGS (i.e., directly measured HGS) and bias-free predicted HGS. The neural basis of true HGS and ΔHGSwas investigated by correlating them to regional gray matter volume (GMV). Statistical analyses were performed to test their sensitivity to longitudinal changes in stroke and major depressive disorder (MDD) patients compared to matched healthy controls (HC).ResultsHGS could be accurately predicted using anthropometric and demographic features, with linear support vector machine (SVM) demonstrating high accuracy. Compared to true HGS, ΔHGSshowed high reassessment reliability and stronger, widespread associations with GMV, especially in motor-related regions. Longitudinal analysis revealed that neither HGS nor ΔHGSeffectively differentiated patients from matched HC at post time-point.ConclusionThe proposed ΔHGSscore exhibited stronger correlations with GMV compared to true HGS, suggesting it better represents the relationship between muscle strength and brain structure. While not effective in differentiating patients from HC at post time-point, the increase in ΔHGSfrom pre to post time-points in patient cohorts may indicate improved utility for monitoring disease progression, treatment efficacy, or rehabilitation effects, warranting further longitudinal validation.
Adoption of Community Adolescent Treatment Support for HIV Care Retention in Greater Accra Region, Ghana
Authors: Green-Harris Margor A. , Nyasulu Thembikile , Ching Jordanne Futu , Kogi Robert , Asampong Emmanuel , Dako-Gyeke Phyllis 
Published: November 2024

AbstractDespite the introduction of efficacious antiretroviral therapy, HIV and AIDS continue to pose a threat to global public health. Community adolescent treatment support programs have shown promising signs of improving adherence retention to care which in turn improves HIV-related health outcomes in this population. However, little is known about the adoption of this program among adolescents in Ghana. This study sought to assess the adoption of community adolescent treatment support among adolescents living with HIV in Tema General Hospital and LEKMA Hospital in the Greater Accra Region, Ghana.A qualitative phenomenological design was carried out at the Tema General Hospital and LEKMA Hospital. Adolescents living with HIV aged 18 to 24 years old who were actively participating in the Community Adolescents Treatment Support (CATS) services were recruited in this study. In addition, healthcare workers involved in the CATS strategy since its inception were recruited. A total of sixteen (16) key informant and in-depth interviews were conducted. The data was transcribed verbatim and imported to NVivo 14.0 software for thematic analysis.It was found that CATS serves as a crucial support system, strengthening peer connections and providing flexible medication pickup. Improved medication adherence, better retention in care, and positive viral load outcomes were evident among participants. However, communication issues and participants consistency pose challenges. Support group meetings werehighly valued by participants. Mobile health services were widely accepted for maintaining connectivity and support. Home visit services faced reluctance due to privacy concerns, and the wider community was perceived as unwelcoming. While challenges persist, including recruitment difficulties and financial support, there is a strong commitment to improving the program’s effectiveness and scalability. Communication strategies, increasing funding support, and intensifying community education and sensitization efforts should be strengthened to reduce stigma and foster broader community inclusivity.
Diffusion Signals of Glial Activation Correlate with Fitness Scores in Parkinson’s Subcortical Gray Matter
Authors: Newman Benjamin T. , Foreman Ryan , Donahue Erin , Jakowec Michael , Petkus Andrew J. , Holschneider Daniel P. , O’Neil Joseph , Schiehser Dawn M. , Petzinger Giselle , Van Horn John Darrell 
Published: November 2024

AbstractThe cholinergic basal forebrain and subcortical gray matter have previously been implicated in Parkinson’s disease (PD) but the relationship between the symptomology of PD, including cognitive impairment, and specific patterns of damage remains unclear. Additionally understanding the impact of fitness, including motor skill fitness, on brain structure remains a gap in knowledge. In this study, we examine a longitudinal cohort of PD patients using advanced microstructural analysis derived from diffusion MRI, alongside volumetric, and connectivity components. These imaging metrics are compared to comprehensive cognitive and motor skill fitness metrics. Though the volumetric components well characterize change across the longitudinal timescale, the microstructural analysis was related to a number of composite cognitive scores including attention, executive function, cognition, language, as well as the level of motor skill fitness. We further assess the connectivity of the cholinergic basal forebrain, particularly the nucleus basalis of Meynert in area 4 (CH4), and find that connectivity between CH4 and the thalamus is associated with latent motor skill fitness. The pattern of microstructural results suggests that increased cellularity, potentially from astrocytic glial cells, may support reduced cognitive decline in individuals with PD as well as higher motor skill fitness.
Acute respiratory distress syndrome and acute kidney injury in critically ill patients: a scoping review protocol about the lung-kidney crosstalk
Authors: Mattedi Francisco Z. , Ribeiro Heitor S. , Busatto Geraldo F. , Carvalho Carlos R. R. , Burdmann Emmanuel A. 
Published: November 2024

ABSTRACTIntroductionAcute respiratory distress syndrome (ARDS) is a risk factor for several adverse clinical outcomes, including mortality. Acute kidney injury (AKI) is one of the most common extrapulmonary complications in ARDS. Despite the high incidence of AKI in patients with ARDS, the lung-kidney crosstalk is not yet fully understood.ObjectiveThis scoping review aims to describe the association between ARDS and AKI in critically ill patients.MethodsWe will follow the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Based on theParticipants,Concept, andContext framework, we will include studies that investigated critically ill patients with ARDS (Participants), describe AKI-related outcomes (Concept), and were conducted in hospitals (Context). A comprehensive literature search will be performed using the MEDLINE, Embase, and LILACS databases without date or language restrictions from database inception until January 2024. Observational studies with retrospective, prospective, and case-control designs will be considered. Two independent reviewers will screen titles and abstracts and perform full-text reviews. Data extraction will be performed by the main reviewer and checked by a second one. Data on the diagnosis of ARDS and follow-up time for AKI-related outcomes will be extracted from the selected evidence. The quantitative results will be synthesized and presented in tables and figures along with a narrative summary.Ethics and disseminationThere is no ethical approval requirement for this scoping review. On completion, the review will be published in a peer-reviewed academic journal and presented at a health conference.
Fixed-Dose Combination Use and Drug Adherence, Healthcare Utilization, and Costs
Authors: Zhang Donglan , Lee Jun Soo , Therrien Nicole L. , Pollack Lisa M. , Jackson Sandra L. , Dong Xiaobei , Rajan Anand , Hong Kai , Moran Andrew E. , Luo Feijun 
Published: November 2024

AbstractBACKGROUNDCombination-pill therapy using fixed-dose combination (FDC) antihypertensives has the potential to improve hypertension control and management. However, combination-pill therapy remains low. This study aims to assess 1) the association between combination-pill therapy and subsequent medication adherence, healthcare utilization, and costs and 2) the potential to mitigate racial and ethnic disparities in medication adherence, among Medicaid beneficiaries.METHODSA retrospective cohort analysis was conducted using the 2017-2021 MerativeTMMarketScan® Medicaid claims database. The study sample included adults aged 18-64 years with hypertension, continuously enrolled one year before and after a random index date of prescribed antihypertensives. Combination-pill therapy was compared with multi-pill therapy. The propensity-score overlap weighting method was used to balance characteristics between individuals using combination- and multi-pill therapy. Logistic models were used for medication adherence, linear models for medication possession ratios (MPRs), negative binomial models for healthcare utilization, and generalized linear models for healthcare costs.RESULTSCompared with multi-pill therapy, combination-pill therapy was associated with improved medication adherence (3.17 in MPR, 95% CI: 2.79 - 3.55), fewer hypertension-related emergency department visits (220 per 1,000 individuals, 95% CI: -235 – -204), fewer hospitalizations (153 per 1,000 individuals, 95% CI: -160 – -146), and lower medical costs ($2,862 per person, 95% CI: -$3,035 – -$2,689). However, disparities in medication adherence between non-Hispanic White and non-Hispanic Black adults existed for both FDC and multi-pill therapy.CONCLUSIONSCombination-pill therapy could improve hypertension management and save costs for the Medicaid program and beneficiaries. These findings may inform policies on FDC antihypertensive coverage and programs.Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
Chromatin Structures from Integrated AI and Polymer Physics Model
Authors: Schultz Eric R , Kyhl Soren , Willett Rebecca , de Pablo Juan J 
Published: November 2024

AbstractThe physical organization of the genome in three-dimensional space regulates many biological processes, including gene expression and cell differentiation. Three-dimensional characterization of genome structure is critical to understanding these biological processes. Direct experimental measurements of genome structure are challenging; computational models of chromatin structure are therefore necessary. We develop an approach that combines a particle-based chromatin polymer model, molecular simulation, and machine learning to efficiently and accurately estimate chromatin structure fromindirectmeasures of genome structure. More specifically, we introduce a new approach where the interaction parameters of the polymer model are extracted from experimental Hi-C data using a graph neural network (GNN). We train the GNN on simulated data from the underlying polymer model, avoiding the need for large quantities of experimental data. The resulting approach accurately estimates chromatin structures across all chromosomes and across several experimental cell lines despite being trained almost exclusively on simulated data. The proposed approach can be viewed as a general framework for combining physical modeling with machine learning, and it could be extended to integrate additional biological data modalities. Ultimately, we achieve accurate and high-throughput estimations of chromatin structure from Hi-C data, which will be necessary as experimental methodologies, such as single-cell Hi-C, improve.
Identification of neuronatin as a SERCA2b regulin-like protein and assessment of its aggregation propensity via coarse grained simulations
Authors: Mariem Omar Ben , Coppi Lara , De Fabiani Emma , Eberini Ivano , Crestani Maurizio 
Published: November 2024

AbstractNeuronatin (NNAT) is small transmembrane protein involved in a wide range of physiological processes, such as white adipose tissue browning and neuronal plasticity, as well as pathological ones, such as Lafora disease caused by the formation of NNAT aggregates. However, its 3D structure is unknown, and its mechanism of action is still unclear. In this study the two most well-known NNAT isoforms (α and β) were modelled and the interaction with the SERCA2b calcium pump was assessed using computational methods. First, molecular docking identified the same binding region as the one described for phospholamban, a thoroughly described SERCA inhibitor. Then, analyses of the flux of water molecules during molecular dynamics simulations highlighted significant similarities between the behavior of SERCA2b when in complex with phospholamban, and when in complex with either NNAT isoform. These results suggest that NNAT could be considered a “regulin-like” protein. Additional all-atom and coarse-grained simulations of multiple copies of NNAT highlighted a significant aggregation potential of both NNAT isoforms, supporting experimental data.Statement of significanceThis study presents the first structural model of neuronatin (NNAT) isoforms α and β. Through molecular docking and molecular dynamics simulations, we propose a NNAT interaction mechanism with the SERCA2b calcium pump similar to that of phospholamban, a known regulin and SERCA inhibitor. Our analyses also suggested a strong aggregation potential of NNAT based on all-atom and coarse-grained simulations, in line with experimental data on its involvement in Lafora disease. These insights suggest NNAT can be considered a “regulin-like” protein, advancing our understanding of its molecular function and contributing to new perspectives in targeting NNAT-related pathologies, as well as reinforcing the role of coarse-grained simulations as a valid tool to assess protein aggregation potential.
NF-κB inhibition in dendritic cells pre-treated with sulforaphane-conjugates induces immunotolerance
Authors: Leiva-Castro Camila , Múnera-Rodríguez Ana M. , Martínez-Bailén Macarena , Carmona Ana T. , López-Enríquez Soledad , Palomares Francisca 
Published: November 2024

AbstractSulforaphane (SFN) has notable health benefits but faces challenges due to poor solubility and delivery. This study explores SFN glycoconjugates’ effects on LPS-induced inflammation in human dendritic cells (DCs), aiming to enhance therapeutic potential against inflammatory diseases. Monovalent SFN-glycoconjugates with mannose (SFNMan) and fucose (SFNFuc) were developed and tested for their anti-inflammatory and immune-modulatory properties in DCs from healthy donors under chronic LPS exposure.Our results revealed that carbohydrate-functionalized SFN improves solubility and effectiveness in suppressing inflammation by targeting the p65 NF-κB pathway, without affecting MAPK signaling. SFN-glycoconjugates induce a tolerogenic immune response, characterized by increased IL-10 production and enhanced regulatory T- and B-cell proliferation. Notably, these effects surpass those of p65 NF-κB inhibition alone, highlighting a distinct and potent regulatory mechanism independent of MAPK pathways.These findings demonstrate the promise of SFN-glycoconjugates as innovative therapeutic agents for inflammatory diseases, offering enhanced anti-inflammatory and immunomodulatory effects through improved delivery and targeted molecular pathways.