bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Subclinical Active Inflammation on IFX Pharmacokinetic Modeling and Disease Progression Assessment: Findings from a Prospective Real-World Study in Inflammatory Bowel Disease Patients
Authors: Magro Fernando , Fernandes Samuel , Patita Marta , Arroja Bruno , Lago Paula , Rosa Isadora , Tavares de Sousa Helena , Ministro Paula , Mocanu Irina , Vieira Ana , Castela Joana , Moleiro Joana , Roseira Joana , Cancela Eugénia , Sousa Paula , Portela Francisco , Correia Luís , Moreira Paula , Dias Sandra , Afonso Joana , Danese Silvio , Peyrin-Biroulet Laurent , Vucicevic Katarina M , Santiago Mafalda 
Published: January 2024

Abstract

Background and aims
Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study’s primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.

Methods
The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model.

Results
The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression.

Conclusion
In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.
Dust and Death: Evidence from the West African Harmattan
Authors: Adhvaryu Achyuta , Bharadwaj Prashant , Fenske James , Nyshadham Anant , Stanley Richard 
Published: January 2024

Abstract
Using two decades of data from 12 low-income countries in West Africa, we show that dust carried by harmattan trade winds increases infant and child mortality. Health investments respond to dust exposure, consistent with compensating behaviours. Despite these efforts, surviving children still exhibit negative health impacts. Our data allow us to investigate differential impacts over time and across countries. We find declining impacts over time, suggesting adaptation. Using national-level measures of macroeconomic conditions and health resources, we find suggestive evidence that both economic development and public health improvements have contributed to this adaptation, with health improvements playing a larger role.
Advanced considerations in survival analysis
Authors: Carnero-Alcázar Manuel , Montero-Cruces Lourdes , Cobiella-Carnicer Javier , Pérez-Camargo Daniel , Maroto Castellanos Luis 
Published: January 2024

Abstract
Investigation of survival during the follow-up period is common in cardiovascular research and has intrinsic issues that require precise knowledge, such as survival or censoring. Besides, as the follow-up period lengthens and events other than mortality are studied, the analysis becomes more complex, so Kaplan–Meier analyses or Cox models are not always sufficient. In this primer, we provide the reader with detailed information on the interpretation of the most common survival analyses and delve into methods to analyse competing risks or alternatives to the conventional methods when the proportional hazards assumption is not met.
The non to moderately dilated root in acute type A aortic dissection: outcomes of the PENN–BERN registry in young, non-syndromic patients
Authors: Mosbahi Selim , Siepe Matthias , Desai Nimesh D , Pregaldini Fabio , Nucera Maria , Berezowski Mikolaj , Kelly John J , Jiang Fei , Zhao Yu , Szeto Wilson Y , Schoenhoff Florian S , Bavaria Joseph E 
Published: January 2024

Abstract

OBJECTIVES
There is an ongoing debate regarding whether patients benefit more from root replacement compared to a reconstruction of the sinuses of Valsalva in acute type A aortic dissection (aTAAD). In those with known or suspected connective tissue disorders, root replacement is considered appropriate. However, there are currently no diameter-based guidelines regarding the best approach in patients with minimally to moderately dilated root and no connective tissue disorders.

METHODS
From January 2005 to December 2022, a two-centre registry of aTAAD was created. Patients were included based on their age (≤60 years), the absence of root entry and dilatation &gt;50 mm and the absence of syndromic hereditable aortic disease. Patients were divided into 2 groups based on the proximal procedure, root reconstruction and root replacement. Propensity score pair matching was performed based on preoperative characteristics.

RESULTS
Cumulative incidence of reintervention at 10 years was slightly higher after root reconstruction 13% vs 3.9% in the matched group (P = 0.040). Survival at 10 years was not affected by the procedure independently of the matching 72.1% vs 71.4% (P = 0.2). Uni- and multivariate Cox regressions showed that a root diameter of &gt;40 mm was associated with a hazard ratio of 7.7 (95% confidence interval 2.6–23) and 5.4 (7–17), respectively, for reoperation for aneurysm and pseudoaneurysm.

CONCLUSIONS
Rate of reoperation due to proximal pseudoaneurysm and aneurysm could be significantly reduced with a lower threshold of 40 mm to replace the aortic root in aTAAD than in elective cases.
‘When age is not a barrier’: an explorative study of nonagenarian patients’ experiences of undergoing percutaneous coronary intervention
Authors: Instenes Irene , Fridlund Bengt , Borregaard Britt , Larsen Alf Inge , Allore Heather , Bendz Bjørn , Deaton Christi , Rotevatn Svein , Fålun Nina , Norekvål Tone M 
Published: January 2024

Abstract

Aims
The recent rise in the number of nonagenarians (age ≥ 90 years) undergoing percutaneous coronary intervention (PCI) has revealed gaps in research, in particular on patients’ experiences. Therefore, the aim of the study was to explore and describe nonagenarians’ internal resources and their experiences of the in-hospital pathway.

Methods and results
Nineteen nonagenarian patients (women n = 9), mean age 91 years, 9 acutely, and 10 electively treated, were consecutively enrolled from a tertiary university hospital from June 2021 to February 2023. In-depth interviews were conducted during hospitalization, audiotaped and transcribed. The interviews were analysed using qualitative content analysis. Three sub-themes emerged from the nonagenarians’ experiences with the PCI treatment trajectory: (i) Taking lifelong responsibility for own physical and mental health describes a population striving to live a healthy life and to stay independent. Physical and mental activities including healthy food choices had been an integral aspect of their lives from early childhood. (ii) Individual internal resources influenced the PCI pathway describes how their internal resources were used, from actively engaging in the decision-making process to withstanding discomfort during the PCI procedure. (iii) The post-PCI pathway was multifaceted describes a short stay at the cardiac ward with individual post-procedural experiences, close monitoring, and preparation for discharge including cardiac rehabilitation.

Conclusion
Nonagenarians undergoing PCI demonstrated a personal incentive to stay healthy and independent. Their internal resources of independence, stoicism, and resilience were used during their in-hospital stay contributing to a successful PCI procedure. Individual cardiac rehabilitation strategies were highlighted after discharge from hospital.
Preferences for innovations in healthcare delivery models in the Swiss elderly population: a latent class, choice modelling study
Authors: Nicolet Anna , Perraudin Clémence , Krucien Nicolas , Wagner Joël , Peytremann-Bridevaux Isabelle , Marti Joachim 
Published: January 2024

Abstract

Background
With the increasing number of people affected by multiple chronic conditions, it is essential for public-health professionals to promote strategies addressing patient needs for coordinated care. We aim to explore preference heterogeneity for better-coordinated care delivery models in Swiss older adults, and identify profiles of individuals more open to healthcare reforms.

Methods
A DCE (discrete choice experiment) survey was developed online and on paper for the Swiss adults aged 50+, following best practice. To elicit preferences, we estimated a latent class model allowing grouping individuals with similar preferences into distinct classes, and examined what background characteristics contributed to specific class membership.

Results
The optimal model identified three classes with different openness to reforms. Class 1 (49%) members were concerned with premium increases and were in favour of integrated care structures with care managed by interprofessional teams. Individuals in class 2 (19%) were younger, open to reforms, and expressed the needs for radical changes within the Swiss healthcare system. Class 3 respondents (32%) were strongly reluctant to changes.

Conclusions
Our study goes beyond average preferences and identifies three distinct population profiles, a majority open to reforms on specific aspects of care delivery, a smallest group in favour radical changes, and a third strongly against changes. Therefore, tailored approaches around healthcare reforms are needed, e.g. explaining the role of interprofessional teams in coordinating care, electronic health records and insurance premium variation.
Analysis of CRISPR–Cas loci distribution in Xanthomonas citri and its possible control by the quorum sensing system
Authors: Martins Paula Maria Moreira , Granato Laís Moreira , Morgan Túlio , Nalin Julia Lopes , Takita Marco Aurélio , Alfenas-Zerbini Poliane , de Souza Alessandra Alves 
Published: January 2024

Abstract
Xanthomonas is an important genus of plant-associated bacteria that causes significant yield losses of economically important crops worldwide. Different approaches have assessed genetic diversity and evolutionary interrelationships among the Xanthomonas species. However, information from clustered regularly interspaced short palindromic repeats (CRISPRs) has yet to be explored. In this work, we analyzed the architecture of CRISPR–Cas loci and presented a sequence similarity-based clustering of conserved Cas proteins in different species of Xanthomonas. Although absent in many investigated genomes, Xanthomonas harbors subtype I-C and I-F CRISPR–Cas systems. The most represented species, Xanthomonas citri, presents a great diversity of genome sequences with an uneven distribution of the CRISPR–Cas systems among the subspecies/pathovars. Only X. citri subsp. citri and X. citri pv. punicae have these systems, exclusively of subtype I-C system. Moreover, the most likely targets of the X. citri CRISPR spacers are viruses (phages). At the same time, few are plasmids, indicating that CRISPR/Cas system is possibly a mechanism to control the invasion of foreign DNA. We also showed in X. citri susbp. citri that the cas genes are regulated by the diffusible signal factor, the quorum sensing (QS) signal molecule, according to cell density increases, and under environmental stress like starvation. These results suggest that the regulation of CRISPR–Cas by QS occurs to activate the gene expression only during phage infection or due to environmental stresses, avoiding a possible reduction in fitness. Although more studies are needed, CRISPR–Cas systems may have been selected in the Xanthomonas genus throughout evolution, according to the cost-benefit of protecting against biological threats and fitness maintenance in challenging conditions.
ProbBreed: a novel tool for calculating the risk of cultivar recommendation in multienvironment trials
Authors: Chaves Saulo F S , Krause Matheus D , Dias Luiz A S , Garcia Antonio A F , Dias Kaio O G 
Published: January 2024

Abstract
Neglecting genotype-by-environment interactions in multienvironment trials (MET) increases the risk of flawed cultivar recommendations for growers. Recent advancements in probability theory coupled with cutting-edge software offer a more streamlined decision-making process for selecting suitable candidates across diverse environments. Here, we present the user-friendly ProbBreed package in R, which allows breeders to calculate the probability of a given genotype outperforming competitors under a Bayesian framework. This article outlines the package’s basic workflow and highlights its key features, ranging from MET model fitting to estimating the per se and pairwise probabilities of superior performance and stability for selection candidates. Remarkably, only the selection intensity is required to compute these probabilities. By democratizing this complex yet efficient methodology, ProbBreed aims to enhance decision-making and ultimately contribute to more accurate cultivar recommendations in breeding programs.
Flatworm Transcriptomes Reveal Widespread Parasitism by Histophagous Ciliates
Authors: Woodcock M Ryan , Powers Kaleigh , Snead Kirsten , Pellettieri Jason 
Published: January 2024

AbstractUnicellular ciliates like Tetrahymena are best known as free-living bacteriovores, but many species are facultative or obligate parasites. These “histophages” feed on the tissues of hosts ranging from planarian flatworms to commercially important fish and the larvae of imperiled freshwater mussels. Here, we developed a novel bioinformatics pipeline incorporating the nonstandard ciliate genetic code and used it to search for Ciliophora sequences in 34 publicly available Platyhelminthes EST libraries. From 2,615,036 screened ESTs, we identified nearly 6,000 high-confidence ciliate transcripts, supporting parasitism of seven additional flatworm species. We also cultured and identified Tetrahymena from nine terrestrial and freshwater planarians, including invasive earthworm predators from the genus Bipalium and the widely studied regeneration models Dugesia japonica and Schmidtea mediterranea. A co-phylogenetic reconstruction provides strong evidence for the coevolution of histophagous Ciliophora with their Platyhelminthes hosts. We further report the antiprotozoal aminoglycoside paromomycin expels Tetrahymena from S. mediterranea, providing new opportunities to investigate the effects of this relationship on planarian biology. Together, our findings raise the possibility that invasive flatworms constitute a novel dispersal mechanism for Tetrahymena parasites and position the Platyhelminthes as an ideal model phylum for studying the ecology and evolution of histophagous ciliates.
Enhancing the health knowledge and health literacy of recently resettled refugees through classroom-based instructional methods
Authors: Agrawal Pooja , Phadke Manali , Du Nan , Hosain Fatima , Koons Leslie , Brown Camille , O’Malley Shannon , Cheng Frances Y 
Published: January 2024

Abstract
Health education can elevate health literacy, which is associated with health knowledge, health-seeking behaviors and overall improved health outcomes. Refugees are particularly vulnerable to the effects of low health knowledge and literacy, which can exacerbate already poor health stemming from their displacement experience. Traditional learning methods including classroom-based instruction are typically how health-related information is presented to refugees. Through a series of interactive classes focused on specific health topics relevant to the resettled refugee population, this study evaluated the effectiveness of a classroom-based health education model in enhancing the health knowledge of recently resettled refugees. We used the Wilcoxon signed-rank test to evaluate differences in pre- and post-class knowledge through test performance. We found a significant improvement in health knowledge in two refugee groups: females and those who were employed. Culturally and socially sensitive considerations including language inclusiveness, class timing, transportation and childcare provisions are important when creating an educational program for individuals with refugee backgrounds. Developing focused approaches to instruction that enhance health knowledge could lead to better health literacy and ultimately improve health-related behaviors and outcomes in the refugee population.
Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy
Authors: Liu Zhou , Julius Peter , Himwaze Cordilia Maria , Mucheleng’anga Luchenga Adam , Chapple Andrew G , West John T , Wood Charles 
Published: January 2024

Abstract

Background
Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis’s effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored.

Methods
To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use.

Results
The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower.

Conclusions
Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.
Loratadine as an Anti-inflammatory Agent Against Clostridium difficile Toxin B
Authors: Xie Ying , Irwin Sophie , Chupina Estrada Andrea , Nelson Becca , Bullock Ashlen , Fontenot Lindsey , Feng Hanping , Sun Mingjun , Koon Hon Wai 
Published: January 2024

Abstract

Background
Clostridium difficile infection (CDI) is a debilitating nosocomial infection. C. difficile produces toxins A and B, which cause inflammation. Existing therapies have issues with recurrence, cost, and safety. We aim to discover a safe, effective, and economical nonmicrobiological therapeutic approach against CDI.

Methods
We included human primary peripheral blood mononuclear cells (PBMCs), fresh human colonic explants, and humanized HuCD34-NCG mice. Toxin A+B+ VPI 10463 and A−B+ ribotype 017 C. difficile strains were used. We used single-cell RNA profiling and high-throughput screening to find actionable toxin B–dependent pathways in PBMCs.

Results
Histamine 1 receptor–related drugs were found among the hit compounds that reversed toxin-mediated macrophage inflammatory protein (MIP) 1α expression in PBMCs. We identified loratadine as the safest representative antihistamine for therapeutic development. Loratadine inhibited toxin B–induced MIP-1α secretion in fresh human colonic tissues. Oral loratadine (10 mg/kg/d) maintained survival, inhibited intestinal CCl3 messenger RNA expression, and prevented vancomycin-associated recurrence in the VPI 10463–infected mice and ribotype 017-infected hamsters. Splenocytes from loratadine-treated mice conferred anti-inflammatory effects to the VPI 10463–infected T/B-cell­–deficient Rag−/− mice. Oral loratadine suppressed human MIP-1α expression in monocytes/macrophages in toxin B–expressing ribotype 017-infected humanized HuCD34-NCG mice.

Conclusions
Loratadine may be repurposed to optimize existing therapies against CDI.
Toward Pedagogies of Decoloniality: Evaluating Teaching Practice and Syllabus Design in IR Undergraduate Modules
Authors: Clarke Helen 
Published: January 2024

Abstract
Undergraduate teaching in international relations (IR) primarily focuses on state-centric topics of sovereignty, anarchy, and power politics, its dominant theories governed by Western interests. However, the implementation of decolonial pedagogies requires more than simply “adding” non-Western theories to curricula. The myth of Europe must be ruptured, revealing its idealized and partisan foundations, uncovering knowledges from the interstices. This article contributes to the pedagogic literature by exploring attempts to decenter the discipline, evaluating teaching practice and syllabus design in three IR undergraduate modules. Drawing on thirty-five semi-structured interviews with lecturers and students, it argues that students benefit from the introduction of decolonial pedagogies, developing broader curricula knowledge, and, crucially, epistemic criticality. Despite these benefits, implementing decolonial praxis in 12-week modules can be challenging. The article suggests starting-points for lecturers seeking to decenter their teaching, calling for pedagogies of decoloniality to be implemented at a departmental level, with faculty and institutional support.
Measuring quality-of-care in treatment of young children with attention-deficit/hyperactivity disorder using pre-trained language models
Authors: Pillai Malvika , Posada Jose , Gardner Rebecca M , Hernandez-Boussard Tina , Bannett Yair 
Published: January 2024

Abstract

Objective
To measure pediatrician adherence to evidence-based guidelines in the treatment of young children with attention-deficit/hyperactivity disorder (ADHD) in a diverse healthcare system using natural language processing (NLP) techniques.

Materials and Methods
We extracted structured and free-text data from electronic health records (EHRs) of all office visits (2015-2019) of children aged 4-6 years in a community-based primary healthcare network in California, who had ≥1 visits with an ICD-10 diagnosis of ADHD. Two pediatricians annotated clinical notes of the first ADHD visit for 423 patients. Inter-annotator agreement (IAA) was assessed for the recommendation for the first-line behavioral treatment (F-measure = 0.89). Four pre-trained language models, including BioClinical Bidirectional Encoder Representations from Transformers (BioClinicalBERT), were used to identify behavioral treatment recommendations using a 70/30 train/test split. For temporal validation, we deployed BioClinicalBERT on 1,020 unannotated notes from other ADHD visits and well-care visits; all positively classified notes (n = 53) and 5% of negatively classified notes (n = 50) were manually reviewed.

Results
Of 423 patients, 313 (74%) were male; 298 (70%) were privately insured; 138 (33%) were White; 61 (14%) were Hispanic. The BioClinicalBERT model trained on the first ADHD visits achieved F1 = 0.76, precision = 0.81, recall = 0.72, and AUC = 0.81 [0.72-0.89]. Temporal validation achieved F1 = 0.77, precision = 0.68, and recall = 0.88. Fairness analysis revealed low model performance in publicly insured patients (F1 = 0.53).

Conclusion
Deploying pre-trained language models on a variable set of clinical notes accurately captured pediatrician adherence to guidelines in the treatment of children with ADHD. Validating this approach in other patient populations is needed to achieve equitable measurement of quality of care at scale and improve clinical care for mental health conditions.