bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological analysis of cognitive load variations during complex information processing
Authors: Armougum Allan , Gaston-Bellegarde Alexandre , Joie-La Marle Chantal , Piolino Pascale 
Published: February 2025

Abstract
Information processing in complex contexts generates higher cognitive demand than in optimal contexts. Though information processing is cognitively less demanding in experts, due to their high level of prior knowledge and considerable number of schemas, a rise in the information complexity in non-optimal context could generate an expertise reversal effect. In our study, we analysed how incidental presentation of information affects cognitive load of train travellers with different expertise levels during navigation in an immersive virtual train station. Analyses of electroencephalography and electrodermal activities as physiological metrics, NASA-Task Load Index as subjective measure and binding memory score as behavioural measure of performance during a recognition phase, helped to quantify cognitive load during the study. With rise in expertise of the investigated train station, participants showed equal or higher cognitive load than participants with lower expertise level, from encoding to recognition phase of the experiment, suggesting an expertise reversal effect. Participants with less expertise did not show any statistically significant difference in cognitive load level from encoding to recognition phase. These findings suggest that complex environmental contexts could contribute to reduce schemas update with increasing expertise level, generating expertise reversal effect.
Early COVID-19 and protection from Omicron in a highly vaccinated population in Ontario, Canada: a matched prospective cohort study
Authors: Shigayeva Altynay , Kandel Christopher , Farooqi Lubna , Zhong Zoe , Gingras Anne-Claude , Coleman Brenda L. , Gilbert Lois , Gold Wayne L. , Major Maria , Mazzulli Tony , Mubareka Samira , Vojicic Jelena , Yang Jingyan , Zhang Pingping , Martin Catherine , Kyaw Moe H. , McLaughlin John M. , McGeer Allison 
Published: February 2025

Abstract

Objectives
Predictions regarding the on-going burden of SARS-CoV-2, and vaccine recommendations, require an understanding of infection-associated immune protection. We assessed whether early COVID-19 provided protection against Omicron infection.

Methods
We enrolled a cohort of adults in Ontario, Canada, with COVID-19 prior to October 2020 (early infection, EI), and a matched cohort with COVID-19 testing and a negative PCR (non-EI). Participants completed baseline surveys then surveys every two weeks until January 2023. Multivariable Cox regression was used to assess factors associated with COVID-19 infection during the first 14 months of Omicron.

Results
Overall, 624 EI (70%) and 175 (77%) non-EI participants met criteria for analysis; 590 (95%) EI and 164 (94%) non-EI had received at least 2 COVID-19 vaccine doses prior to Omicron. Of 624 EI, 175 (28%) had one SARS-CoV-2 re-infection and 8 (1.3%) had two, compared to 84 (48%) non-EI participants with one, 5 (2.9%) with two and 1 (0.6%) with 3 infections (P < 0.0001). In multivariable analysis of risk factors for Omicron infection, the overall hazard ratio (HR, 95%CI) associated with EI was 0.56 (0.43–0.74); HRs for BA.1/2, BA.4/5 and mixed BA.5/BQ.1/XBB periods were 0.66 (0.45–0.97), 0.44 (0.28–0.68) and 0.71 (0.32–1.56). EI and BA.1/2 infection combined reduced later Omicron infection (HR 0.07 (0.03–0.21) compared to no prior infection. Older age, non-White ethnicity, no children in household, and lower neighbourhood income were associated with reduced risk of infection.

Conclusions
In our highly vaccinated population, early SARS-CoV-2 infection was associated with a 44% reduction in symptomatic COVID-19 during the first 14 months of Omicron, providing significant protection against re-infection for more than 2 years.
The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response
Authors: Chen Hui , Xu Yue , Chen Dingshan , Xiao Di , Yang Bing , Wang Wenqi , Han Han 
Published: February 2025

Abstract
The platinum-based compounds are widely used in treating various types of cancer through their heavy metal component platinum. However, the development of chemoresistance often limits their clinical effectiveness. In this study, we report the roles of heavy metal response and its associated Hippo pathway in regulating platinum-based chemotherapy. Our data show that the MTF1-dependent heavy metal response induces cancer cell resistance to platinum-based compounds both in vitro and in vivo. This resistance is mitigated by Hippo pathway-mediated phosphorylation of MTF1. Moreover, pharmacological activation of the Hippo pathway sensitizes cancer cells to platinum-based compounds. Clinically, lung adenocarcinoma (LUAD) patients with high MTF1 activity exhibit poor overall survival rates, and Hippo pathway inactivation is positively correlated with elevated MTF1 transcriptional activity in platinum-treated LUAD patients. Collectively, our findings not only unveil a critical role of the Hippo-MTF1 pathway in regulating the response to platinum-based chemotherapy, but also suggest new strategies to enhance its efficacy by targeting the heavy metal response.
Development of the pulmonary fibrosis, pulmonary vascular resistance, six minute walk distance, B-type natriuretic peptide, age (PVD-B65) risk score for patients with chronic lung disease and pulmonary hypertension
Authors: Gayen Shameek , Pescatore Jay , Bittner Matthew , Naranjo Mario , Criner Gerard J. , Weaver Sheila ,   Temple Lung Center Pulmonary Vascular Disease Working Group, D’Alonzo Gilbert , Illipparambil Lijo , Rali Parth , Pourshahid Seyedmohammad 
Published: February 2025

Abstract

Background
Pulmonary hypertension (PH) confers increased mortality in patients with chronic lung disease, yet there remains a lack of validated risk assessment tools to prognosticate these patients. We aimed to create a risk assessment tool to stratify patients with chronic lung disease and PH by risk of one-year mortality from time of PH diagnosis.

Methods
This was a retrospective cohort study of patients with chronic lung disease and PH. We identified predictors of one-year mortality via multivariable Cox regression and assigned point values to the identified predictors based on their hazard ratios to comprise the risk score. Patients were stratified into low, intermediate, and high-risk based on total scores. Kaplan–Meier survival analysis comparing the stratified groups was performed. Internal statistical validation was performed via Cox regression with bootstrapping.

Results
The identified predictors of one-year mortality that comprised our risk assessment tool were pulmonary fibrosis without emphysema, pulmonary vascular resistance > 5 WU, six-minute walk distance < 150 m, BNP > 200 pg/mL, and age > 65 years (PVD-B65). Once patients were stratified into the three risk groups, Kaplan–Meier survival analysis demonstrated significant differences in one-year survival between the subgroups (logrank p = 0.002). The risk assessment model demonstrated internal validation via bootstrapping (p < 0.05).

Conclusion
The PVD-B65 risk assessment tool is a novel, internally validated one-year mortality risk calculator for patients with chronic lung disease and PH that encompasses factors related to pulmonary parenchymal and vascular remodeling. It may help risk stratify and guide therapeutic interventions in patients with chronic lung disease and PH.
Developing a master of science in health research ethics program in Northern Nigeria: a needs assessment
Authors: Bieniek Caitlin , Tsiga-Ahmed Fatimah I. , Adamu Aishatu L. , Wudil Usman J. , Wester C. William , Iliyasu Zubairu , Aliyu Muktar H. , Gordon Elisa J. , Rose Elizabeth S. 
Published: February 2025

Abstract

Background
Nigeria is an emerging hub of biomedical research, requiring additional trained bioethicists for ethical oversight of research studies. There are currently two graduate-level health research ethics programs in Nigeria. However, both are in the southern part of the country and no such training programs exist in the north. Strengthening the health research ethics skills and knowledge of Nigerian researchers across the country is necessary given the growing genetics research infrastructure.

Methods
To inform the creation of a Master of Science in Health Research Ethics program in northern Nigeria, we conducted a needs assessment comprised of semi-structured interviews with nine Nigerian bioethics experts. We used the Interpretative Phenomenological Analysis (IPA) method to analyze interview transcriptions. Two authors independently read and coded each respondent’s transcript to identify emergent themes that represented each respondent’s answers. Within these overarching themes, the data points were grouped into subthemes.

Results
Four primary themes emerged with ten subthemes. Respondents believed that the program can fill a gap and strengthen capacity in health research ethics. They emphasized that the curriculum should be developed with an interdisciplinary lens and locally contextualized, and that students should be taught how to think critically through ethical scenarios. Respondents stressed that program leaders should recruit faculty and students locally who have the bandwidth to participate in the program. Finally, respondents noted the program should have university support to be sustainable.

Conclusion
Our findings will guide the creation of a master’s degree program that aims to build capacity in health research ethics in northern Nigeria and enhance the country’s growing prominence in global biomedical research. Through our needs assessment, we identified structural and content factors that can guide us in leveraging the strengths of the local institution and leaders in health research ethics while mitigating challenges in establishing this program.
Opioid consumption frequency and its associations with potential life problems during opioid agonist treatment in individuals with prescription-type opioid use disorder: exploratory results from the OPTIMA Study
Authors: Bouthillier Anne , Bastien Gabriel , McAnulty Christina , Bakouni Hamzah , Le Foll Bernard , Socias M. Eugenia , Jutras-Aswad Didier 
Published: February 2025

Abstract

Background
Traditional treatment approaches for prescription-type opioid use disorder (POUD), centered on abstinence, have limitations and hinder the development of interventions that meet the needs of people with POUD. Reduction in use without complete abstinence presents a promising avenue for intervention enhancement, but supporting data is scarce regarding its translation into positive patient outcomes. This study explores whether reducing opioid use frequency (OUF) during opioid agonist treatment correlates with reduced potential life problems in individuals with POUD, including those using fentanyl.

Methods
This study is an exploratory analysis of the OPTIMA trial, a pragmatic, open-label, randomized controlled study comparing the effectiveness of flexible take-home dosing of buprenorphine/naloxone and supervised methadone in reducing opioid use amongst individuals with POUD. OUF was assessed every two weeks for 24 weeks after treatment initiation using the Timeline Followback. Potential life problems were evaluated at baseline and study completion using the Addiction Severity Index Self-Report. The 114 participants who completed both baseline and end-of-study questionnaires were included. A repeated-measures generalized linear mixed model (GLMM) was used to evaluate the influence of OUF on potential life problems.

Results
Reducing OUF was significantly associated with fewer problems related to medical status (p = 0.049), psychiatric status (p = 0.019), and alcohol problem severity (p = 0.001). The interaction was non-significant for employment (p = 0.264), family status (p = 0.352) and legal status (p = 0.050). Life improvements emerged with ≤ 21 days of opioid use per 28-day period.

Conclusion
Findings underscore the significance of harm reduction goals focusing on opioid use reduction, which translated in improvements across many life domains.

Trial registration
Study was registered with ClinicalTrials.gov (NCT03033732) prior to participant enrollment.
Fractional hitting sets for efficient multiset sketching
Authors: Rouzé Timothé , Martayan Igor , Marchet Camille , Limasset Antoine 
Published: February 2025

Abstract
The exponential increase in publicly available sequencing data and genomic resources necessitates the development of highly efficient methods for data processing and analysis. Locality-sensitive hashing techniques have successfully transformed large datasets into smaller, more manageable sketches while maintaining comparability using metrics such as Jaccard and containment indices. However, fixed-size sketches encounter difficulties when applied to divergent datasets. Scalable sketching methods, such as , provide valuable solutions but still lack resource-efficient, tailored indexing. Our objective is to create lighter sketches with comparable results while enhancing efficiency. We introduce the concept of Fractional Hitting Sets, a generalization of Universal Hitting Sets, which cover a specified fraction of the k-mer space. In theory and practice, we demonstrate the feasibility of achieving such coverage with simple but highly efficient schemes. By encoding the covered k-mers as super-k-mers, we provide a space-efficient exact representation that also enables optimized comparisons. Our novel tool, , implements this scheme, and experimental results with real bacterial collections closely match our theoretical findings. In comparison to , achieves similar outcomes while utilizing an order of magnitude less space and memory and operating several times faster. This highlights the potential of our approach in addressing the challenges presented by the ever-expanding landscape of genomic data. is an open-source software and can be accessed at https://github.com/TimRouze/supersampler. The data required to reproduce the results presented in this manuscript is available at https://github.com/TimRouze/supersampler/experiments.
Radiological assessment of cup anteversion with a novel 3D-printed highly-porous titanium dual mobility cup
Authors: Puteo Nicole , Valentino Edoardo Matteo , Davidoni Vittorio , Tigani Domenico 
Published: February 2025

Abstract

Background
Cup anteversion after primary total hip arthroplasty (THA) with monobloc dual mobility cups (DMC) is difficult to measure on anterior-posterior (AP) pelvic radiographs because of the implant radiopacity and cup design which do not allow for an accurate visualization of the radiographic projection of the cup equatorial rim and the femoral head. This study aims to radiographically investigate on the reliability and accuracy of different measurement methods for cup anteversion in monobloc DMC THA, by comparing a novel titanium cup with conventional cup designs.

Methods
97 THAs with a monobloc 3D-printed titanium DMC were radiographically assessed for cup radiographic anteversion (RA) one month postoperatively. RA were measured by three blinded observers through Lewinnek, Woo-Morrey methods and an open access mathematical software (GeoGebra), used as reference method. Intra- and interobserver reliability of RA measurements were evaluated for each method using intraclass correlation coefficient (ICC). Accuracy was assessed comparing Lewinnek and Woo-Morrey methods with GeoGebra. Moreover, further 98 THAs with conventional different brand DMC were radiographically assessed as control group by using the same methods.

Results
ICC for intra- and interobserver reliability for RA measurements with GeoGebra, Lewinnek and Woo-Morrey methods were 0.975–0.980, 0.978 − 0.965, and 0.979 − 0.958, respectively, for the titanium DMC group. Lewinnek resulted more accurate for RA than Woo-Morrey, differing by + 0.4° (p = 0.06) and + 4.4° (p < 0.001) from GeoGebra, respectively. ICC for intra- and interobserver reliability for GeoGebra, Lewinnek and Woo-Morrey methods were 0.848 − 0.756, 0.843 − 0.801, and 0.965 − 0.958, respectively, for the control DMC group. Lewinnek and Woo-Morrey methods differed by -2.3° and + 5.1° from GeoGebra, respectively (p < 0.001).

Conclusions
RA measurements are more consistent, repeatable and accurate with a titanium DMC than standard DMC, due to the minor radiopacity of the former cup which enable RA measurements on AP radiographs. Conversely, RA measurements of conventional DMC are more consistent but less accurate if performed on cross-table lateral radiographs by Woo-Morrey method than AP radiographs.
Generalized pustular psoriasis: a multicentric study on patient characteristics and clinical burden
Authors: Livideanu Cristina Bulai , Gottlieb Jérémy , Jullien Denis , Passeron Thierry , Vildy Sophie , Delaporte Emmanuel , Paul Carle , Chollet Julien , Najean Marie , San Denis , Taieb Charles , Charles Bénédicte , Mahe Emmanuel , Becherel Pierre-André , Misery Laurent 
Published: February 2025

Abstract
The objective of this study was to assess the demographic characteristics and impact on quality of life (QoL) of patients with PPG in France through a multicentre study. The results of the study are as follows: The PRO [PUSH-D, PHQ-9 et GAD-7] revealed that more than half of the patients exhibited a significant impact on their quality of life. High scores for fatigue, stress, skin and joint pain were reported, with 65% of patients at risk of mild to severe depression. The clinical burden was also assessed. A total of 48.8% of patients were hospitalised, while 39% took sick leave. This study is the first to assess the PUSH-D, PHQ-9 and GAD-7 scores in patients with PPG, which highlighted a significant clinical burden and negative impact on their daily lives.
The transcription factor combination MEF2 and KLF7 promotes axonal sprouting in the injured spinal cord with functional improvement and regeneration-associated gene expression
Authors: Attwell Callan L. , Maldonado-Lasunción Inés , Eggers Ruben , Bijleveld Bastiaan A. , Ellenbroek Ward M. , Siersema Natascha , Razenberg Lotte , Lamme Dédé , Fagoe Nitish D. , van Kesteren Ronald E. , Smit August B. , Verhaagen Joost , Mason Matthew R. J. 
Published: February 2025

Abstract

Background
Axon regeneration after injury to the central nervous system (CNS) is limited by an inhibitory environment but also because injured neurons fail to initiate expression of regeneration associated genes (RAGs). The potential of strong RAG expression to promote regeneration in the CNS is exemplified by the conditioning lesion model, whereby peripheral nerve injury promotes regeneration of centrally projecting branches of the injured neurons. RAG expression could potentially be induced by delivery of the right set of transcription factors (TFs). We here aim to identify TF combinations that activate this program.

Methods
We first analysed binding site motifs in promoters of the RAG program to identify nine candidate growth-promoting TFs. These were systematically screened in vitro to identify combinations that had potent neurite-growth promoting activity. Next, adeno-associated viral vectors were used to express these TF combinations in vivo in L4/L5 dorsal root ganglia to test whether they would promote regeneration in a spinal cord injury model (dorsal column lesion) in female rats. To determine whether they could activate the RAG program we carried out gene expression profiling on laser-dissected dorsal root ganglion neurons specifically expressing these TF combinations, and of DRG neurons that had been axotomized.

Results
Promoter analysis identified ATF3, Jun, CEBPD, KLF7, MEF2, SMAD1, SOX11, STAT3 and SRF as candidate RAG-activating TFs. In vitro screening identified two TF combinations, KLF7/MEF2 and ATF3/KLF7/MEF2, that had potent neurite-growth promoting activity, the latter being the more powerful. In vivo, KLF7/MEF2, but not ATF3/KLF7/MEF2 or KLF7 or MEF2 alone, promoted axonal sprouting into the dorsal column lesion site and led to improved functional recovery. Gene expression profiling revealed that unexpectedly, the MEF2-VP16 construct used had little transcriptional activity in vivo, suggesting additional steps may be required to achieve full MEF2 activity. All combinations except MEF2 alone induced RAG expression mirroring that induced by axotomy to significant extents, while ATF3/KLF7/MEF2, KLF7 and ATF3, but not KLF7/MEF2 also induced apoptosis-related genes which may hinder regeneration.

Conclusions
The TF combination KLF7/MEF2 partially mimics the conditioning lesion effect, inducing axonal sprouting into a dorsal column lesion and driving significant RAG expression, and also promotes functional improvement.
Blood molecular subtypes to guide precision treatment strategies in systemic juvenile idiopathic arthritis
Authors: Baek In-Woon , Rhim Jung Woo , Park Kyung-Su , Kim Ki-Jo 
Published: February 2025

Abstract

Background
Systemic juvenile idiopathic arthritis (sJIA) is the most severe subtype of JIA, with a combination of diverse clinical manifestations and a variable clinical course. A comprehensive understanding of molecular signatures at the systems level and the discovery of molecular subtypes are the initial steps toward personalized medicine in sJIA.

Methods
A blood transcriptomic dataset was collected from patients with systemic JIA (sJIA) (n = 168), polyarticular JIA (n = 254), oligoarticular JIA (n = 96), enthesitis-related arthritis (n = 40), and healthy controls (n = 220). Gene expression profiles were filtered for differentially expressed genes and unsupervised clustering, gene set enrichment, and network-based centrality analyses. The molecular signatures of three novel sJIA subgroups (designated as C1, C2, and C3) were investigated, focusing on their distinct features and treatment responses.

Results
Neutrophil degranulation and the IL-1 signaling pathway were the shared key processes for the three subgroups. Proinflammatory signals, including TNF, IL-6, TLR, and G-CSF signaling pathways, were identified with variation across the subgroups. C1 was the most inflammatory subset with a high-risk profile for macrophage activation syndrome. The C2 subset had the most activated IL-1 and IL-18 signaling pathways. C2 and C3 have higher levels of interferon-stimulated signatures. In a canakinumab-treated dataset, treatment response was correlated with IL1B expression and NF-κB signaling pathway, and neutrophil activation-associated processes were effectively suppressed in a good responder group. GSK3B and p38 MAPK inhibitors showed a significant counteracting effect on the perturbed gene expression of sJIA.

Conclusions
Neutrophil activation was the key feature in active sJIA. The three molecular subtype scheme enables the formulation of precision medicine strategies in sJIA.