bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct trajectories of treatment response to mepolizumab toward remission in patients with severe eosinophilic asthma
Authors: Hamada Yuto , Thomas Dennis , Harvey Erin S. , Stevens Sean , Fricker Michael , Lewthwaite Hayley , McDonald Vanessa M. , Gillman Andrew , Hew Mark , Kritikos Vicky , Upham John W. , Gibson Peter G. 
Published: October 2024

BackgroundPatients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission.MethodsData from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6 and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis.ResultsWe identified three trajectory groups: Group 1, “Responsive asthma with less OCS use” (n=170); Group 2, “Responsive late-onset asthma” (n=58); and Group 3, “Obstructed and less responsive asthma” (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to Group 3 with 5.7% (p<0.001). Baseline predictors for assigned groups included lower OCS dose in Group 1; greater forced expiratory volume in 1 s percentage predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose and nasal polyps in Group 2; with Group 3 as the reference.ConclusionsTreatment response to mepolizumab in severe eosinophilic asthma follows three trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.
Effect of CPAP therapy on blood pressure in patients with obstructive sleep apnoea: a worldwide individual patient data meta-analysis
Authors: Pengo Martino F. , Schwarz Esther I. , Barbé Ferran , Cistulli Peter A. , Drager Luciano F. , Fava Cristiano , Fuchs Flávio D. , Ip Mary S.M. , Loffler Kelly A. , Lui Macy M.S. , Martínez-García Miguel Ángel , McEvoy Doug , Peker Yüksel , Phillips Craig L. , Quinnell Tim , Soranna Davide , Steier Joerg , Stradling John R. , Zambon Antonella , Parati Gianfranco 
Published: October 2024

BackgroundObstructive sleep apnoea (OSA) is associated with hypertension, and OSA treatment can reduce systolic blood pressure (SBP) and diastolic blood pressure (DBP), but with a modest mean effect size and vast heterogeneity among studies. The aim of this individual patient data (IPD) meta-analysis was to understand which OSA phenotypes could benefit the most in terms of BP reduction.MethodsA systematic review of randomised controlled trials that compared continuous positive airway pressure (CPAP) with either passive or active treatment was conducted. Studies were eligible if they included adult patients with OSA diagnosed by full polysomnography or cardiorespiratory polygraphy (defined as apnoea–hypopnoea index >5 events·h−1) and if BP was measured both before and after CPAP treatment.ResultsIn total, 36 parallel studies (n=9434 patients) were included. CPAP treatment was associated with BP reduction in patients with uncontrolled office SBP only, while BP was not reduced by CPAP in patients with controlled BP (SBP −2.6versus0 mmHg; p<0.0001; DBP −1.7versus−1 mmHg; p=0.091). Differences were seen also when BP changes were compared between patients aged ≤60versus>60 years after multiple imputation only (p=0.0127 for SBP and p=0.017 for DBP). No differences were seen in terms of BP reduction when comparing patients with/without severe nocturnal hypoxia.ConclusionsThis IPD meta-analysis of the BP effects of OSA treatment with CPAP shows that OSA patients with uncontrolled BP at baseline benefit the most from CPAP therapy in terms of BP reduction. These results have important implications for the decision on how to best manage arterial hypertension associated with OSA.
Ansa cervicalis stimulation effects on upper airway patency: a structure-based analysis
Authors: Li Yike , Schwartz Alan R. , Zealear David , Shotwell Matthew S. , Hall Megan E. , Lindsell Christopher J. , Budnick Holly A. , Bellotto Silvana , Kent David T. 
Published: October 2024

RationaleAnsa cervicalis stimulation (ACS) of the infrahyoid muscles has been proposed as a neurostimulation therapy for obstructive sleep apnoea (OSA). ACS stabilises the pharynx by pulling it caudally, but its specific effects on flow limitation caused by palatal, oropharyngeal lateral wall, tongue base, or epiglottis collapse remains unclear.ObjectivesTo quantify the effect of ACS on collapsibility of different pharyngeal flow-limiting structures.MethodsParticipants with OSA underwent bilateral ACS during drug-induced sleep endoscopy. Maximum inspiratory airflow was assessed over a range of positive airway pressures while ACS was applied. The flow-limiting structure for each breath was classified based on manometric and endoscopic findings and a linear mixed-effects model characterised their response to ACS. The influence of patient characteristics was explored with univariate models.Measurements and main results41 participants yielded 1761 breaths for analysis. On average, bilateral ACS decreased the observed pharyngeal critical closing (PCRIT) and opening (POPEN) pressures by −3.0 (95% CI −3.6–−2.3) and −3.7 (−4.4–−3.0) cmH2O, respectively (p<0.001). During tongue base obstruction, modelled ACS effects forPCRITandPOPENwere −2.0 (−2.7–−1.4) and −3.1 (−3.8–−2.4) cmH2O, respectively (p<0.001). Greater reductions were generally observed for other flow-limiting structures. A lower apnoea–hypopnea index was associated with a greater decrease inPOPEN(p<0.01). Other patient characteristics, including body mass index, did not influencePCRITorPOPEN(p>0.05).ConclusionsBilateral ACS decreased collapsibility of all airway flow-limiting structures. ACS generally had greater effects on palatal, oropharyngeal lateral wall and epiglottic collapse than the tongue base.
Metagenomic assemblies tend to break around antibiotic resistance genes
Authors: Abramova Anna , Karkman Antti , Bengtsson-Palme Johan 
Published: October 2024

Abstract
Background
Assembly of metagenomic samples can provide essential information about the mobility potential and taxonomic origin of antibiotic resistance genes (ARGs) and inform interventions to prevent further spread of resistant bacteria. However, similar to other conserved regions, such as ribosomal RNA genes and mobile genetic elements, almost identical ARGs typically occur in multiple genomic contexts across different species, representing a considerable challenge for the assembly process. Usually, this results in many fragmented contigs of unclear origin, complicating the risk assessment of ARG detections. To systematically investigate the impact of this issue on detection, quantification and contextualization of ARGs, we evaluated the performance of different assembly approaches, including genomic-, metagenomic- and transcriptomic-specialized assemblers. We quantified recovery and accuracy rates of each tool for ARGs both from in silico spiked metagenomic samples as well as real samples sequenced using both long- and short-read sequencing technologies.

Results
The results revealed that none of the investigated tools can accurately capture genomic contexts present in samples of high complexity. The transcriptomic assembler Trinity showed a better performance in terms of reconstructing longer and fewer contigs matching unique genomic contexts, which can be beneficial for deciphering the taxonomic origin of ARGs. The currently commonly used metagenomic assembly tools metaSPAdes and MEGAHIT were able to identify the ARG repertoire but failed to fully recover the diversity of genomic contexts present in a sample. On top of that, in a complex scenario MEGAHIT produced very short contigs, which can lead to considerable underestimation of the resistome in a given sample.

Conclusions
Our study shows that metaSPAdes and Trinity would be the preferable tools in terms of accuracy to recover correct genomic contexts around ARGs in metagenomic samples characterized by uneven coverages. Overall, the inability of assemblers to reconstruct long ARG-containing contigs has impacts on ARG quantification, suggesting that directly mapping reads to an ARG database should be performed as a complementary strategy to get accurate ARG abundance and diversity measures.
Outcome of laparoscopic feeding jejunostomy, comparison of a pure laparoscopic technique with Witzel’s tunnel to open technique: a retrospective cohort study
Authors: Komek Sumet , Limpakan Sirikan , Tanprasert Peticha , Chakrabandhu Bandhuphat 
Published: October 2024

Abstract
Introduction
Obstructive upper GI cancer commonly uses feeding jejunostomy as a standard procedure. Surgeons implemented laparoscopic feeding jejunostomy via minimally invasive surgery, employing a variety of techniques. This study assessed the perioperative results, safety, and costs associated with laparoscopic versus open jejunostomy surgeries. We used only Witzel’s tunnel and standard laparoscopic instruments.

Patients and methods
We collected data from all patients who underwent feeding jejunostomy between January 2016 and June 2018. We recorded pertinent data on baseline, surgical outcomes, postoperative results, complications, and costs. The study excluded patients with jejunostomy as a conversion or an addition.

Result
We divided the 74 patients into 2 groups: 30 underwent laparoscopy and 44 underwent open surgery. The mean operational times were 89.67 and 91.64 min and showed no statistically significant difference (p = 0.678). The mean morphine dosage was significantly lower in the laparoscopic group (3.3 vs. 7.19, p = < 0.001). Laparoscopic surgery lowered the median time of feeding initiation, feeding accomplished, and postoperative stay, although none of these reached statistical significance. There were significantly higher surgical expenses in the laparoscopic group (16,410 vs. 11,685 Thai Baht) (p < 0.001); however, median overall expenditures did not significantly differ (105,147 vs. 116,198 Thai Baht) (p = 0.387). Laparoscopic versus open surgery had similar incidences of postoperative complications (20% vs. 25%, p = 0.846). The feeding tube catheter location was infection-free in all patients in our study.

Conclusion
Laparoscopic jejunostomy feeding was safe, and postoperative morphine consumption was lower. Increasing operational costs did not have a significant impact on overall expenditures. Witzel’s tunnel may reduce jejunostomy site infections.
Perceptions and attitudes about the contribution of the environment to childhood cancer: a pilot study in a medical guild and undergraduate students
Authors: Jarquin-Yañez Lizet , Cruz Eunice Tello , Martinez-Acuña Monica Imelda , Calderon-Hernandez Jaqueline 
Published: October 2024

Abstract
Background
Identifying and recognizing environmental risk factors for childhood cancer is crucial to prevent it. Medical guild are the first contact to monitor children’s health. Therefore, courses about the contribution of chemical toxins in the environment and health outcomes such as cancer should be included in their professional training. This study aimed to evaluate the perceptions and attitudes of a medical guild and undergraduate students in health sciences about the contribution of the environment to childhood cancer.

Methods
A pilot study was conducted, an online survey including thirteen questions was shared among medical guild members and undergraduate students in health sciences. Frequencies, percentages, and chi-square homogeneity tests were calculated to compare groups.

Results
Genetic factors ranked as the first possible cause of childhood cancer (88.2% medical guild and 97.7% undergraduate students). However, 70.6% of medical guild and 64.6% of undergraduate students reported that they have ever suspected that childhood cancer could be related to the environmental conditions in which children live. More than 95% of the participants reported that they would find it useful to have more knowledge about environmental risks and cancer. When data were analyzed by profession (medical guild) and academic year (undergraduate students), no significant differences were observed. Nonetheless, comparisons by academic discipline between undergraduate students, showed that a higher percentage of medicine and environmental sciences and health (over 98%) reported environmental exposure as risk factors associated with childhood cancer compared to 75% from physiotherapy, (p = 0.001).

Conclusions
In this study, the environmental contribution to childhood cancer is not clear among the medical guild and undergraduate students. They should be trained on the topic of cancer and the environment.
Combined associations of physical activity, diet quality and their changes over time with mortality: findings from the EPIC-Norfolk study, United Kingdom
Authors: Aryannezhad Shayan , Mok Alexander , Imamura Fumiaki , Wareham Nicholas J. , Brage Soren , Forouhi Nita G. 
Published: October 2024

Abstract
Background
Physical activity (PA) and diet quality have each been shown to be inversely associated with mortality but their combined impact on longevity has been less explored, particularly when considering their changes over time. This study aimed to examine the separate and combined associations of PA, diet quality and their changes over time with mortality outcomes.

Methods
A prospective cohort study was performed on 9349 adults aged 40 to 79 years from the population-based European Prospective Investigation into Cancer in Norfolk Study, with repeated measurements of PA and diet (from 1993 till 2004) and subsequent follow-up till 2022 (median follow-up 18.8 years). Validated questionnaires were used to derive physical activity energy expenditure (PAEE) as a proxy of total PA and adherence to the Mediterranean diet score (MDS, range 0–15 points) as an indicator of overall diet quality, and their changes over time (∆PAEE and ∆MDS). Cox regression models adjusted for potential confounders and mediators were used to estimate hazard ratios (HRs) and 95% CIs.

Results
Over 149,681 person-years of follow-up, there were 3534 deaths. In adjusted models, for each 1-SD difference in baseline PAEE (4.64 kJ/kg/day), ∆PAEE (0.65 kJ/kg/day per year), baseline MDS (1.30 points) and ∆MDS (0.32 points per year), HRs (95% CI) for all-cause mortality were 0.90 (0.86 to 0.94), 0.89 (0.85 to 0.93), 0.95 (0.91 to 0.99) and 0.93 (0.90 to 0.97), respectively. Compared with participants with sustained low PAEE (< 5 kJ/kg/day) and low MDS (< 8.5 points), those with sustained high PAEE and high MDS had lower all-cause mortality (HR 0.78; 95% CI: 0.68–0.91), as did those who improved both PAEE and MDS (0.60; 0.44–0.82). There was no evidence of interaction between PA and diet quality exposures on mortality risk. Population impact estimates suggested that if all participants had maintained high levels of PA and diet quality consistently, cumulative adjusted mortality rate would have been 8.8% (95% CI: 2.4 to 15.3%) lower.

Conclusions
These findings suggest that adopting and maintaining higher levels of PA and diet quality are associated with lower mortality. Significant public health benefits could be realised by enabling active living and healthy eating through adulthood.
The role of two major nucleoid-associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation
Authors: Strzałka Agnieszka , Mikołajczyk Jakub , Kowalska Klaudia , Skurczyński Michał , Holmes Neil A. , Jakimowicz Dagmara 
Published: October 2024

Abstract
Background
Streptomyces are sporulating soil bacteria with enormous potential for secondary metabolites biosynthesis. Regulatory networks governing Streptomyces coelicolor differentiation and secondary metabolites production are complex and composed of numerous regulatory proteins ranging from specific transcriptional regulators to sigma factors. Nucleoid-associated proteins (NAPs) are also believed to contribute to regulation of gene expression. Upon DNA binding, these proteins impact DNA accessibility. Among NAPs, HU proteins are the most widespread and abundant. Unlike other bacteria, the Streptomyces genomes encode two HU homologs: HupA and HupS, which differ in structure and expression profile. However, it remained unclear whether the functions of both homologs overlap. Additionally, although both proteins have been shown to bind the chromosome, their rolesin transcriptional regulation have not been studied so far.

Results
In this study, we explore whether HupA and HupS affect S. coelicolor growth under optimal and stressful conditions and how they control global gene expression. By testing both single and double mutants, we address the question of the complementarity of both HU homologs. We show that the lack of both hup genes led to growth and sporulation inhibition, as well as increased spore fragility. We also demonstrate that both HU homologs can be considered global transcriptional regulators, influencing expression of between 2% and 6% genes encoding among others proteins linked to global regulatory networks and secondary metabolite production.

Conclusions
We identify the independent HupA and HupS regulons, as well as genes under the control of both HupA and HupS proteins. Our data indicate a partial overlap between the functions of HupA and HupS during S. coelicolor growth. HupA and HupS play important roles in Streptomyces regulatory network and impact secondary metabolite clusters.
Biosensor-based growth-coupling as an evolutionary strategy to improve heme export in Corynebacterium glutamicum
Authors: Krüger Aileen , Göddecke Janik , Osthege Michael , Navratil Luis , Weber Ulrike , Oldiges Marco , Frunzke Julia 
Published: October 2024

AbstractThe iron-containing porphyrin heme is of high interest for the food industry for the production of artificial meat as well as for medical applications. Recently, the biotechnological platform strain Corynebacterium glutamicum has emerged as a promising host for animal-free heme production. Beyond engineering of complex heme biosynthetic pathways, improving heme export offers significant yet untapped potential for enhancing production strains. In this study, a growth-coupled biosensor was designed to impose a selection pressure on the increased expression of the hrtBA operon encoding an ABC-type heme exporter in C. glutamicum. For this purpose, the promoter region of the growth-regulating genes pfkA (phosphofructokinase) and aceE (pyruvate dehydrogenase) was replaced with that of PhrtB, creating biosensor strains with a selection pressure for hrtBA activation. Resulting sensor strains were used for plate-based selections and for a repetitive batch f(luorescent)ALE using a fully automated laboratory platform. Genome sequencing of isolated clones featuring increased hrtBA expression revealed three distinct mutational hotspots: (i) chrS, (ii) chrA, and (iii) cydD. Mutations in the genes of the ChrSA two-component system, which regulates hrtBA in response to heme levels, were identified as a promising target to enhance export activity. Furthermore, causal mutations within cydD, encoding an ABC-transporter essential for cytochrome bd oxidase assembly, were confirmed by the construction of a deletion mutant. Reversely engineered strains showed strongly increased hrtBA expression as well as increased cellular heme levels. These results further support the proposed role of CydDC as a heme transporter in bacteria. Mutations identified in this study therefore underline the potential of biosensor-based growth coupling and provide promising engineering targets to improve microbial heme production.
Planning for and Assessing Rigor in Rapid Qualitative Analysis (PARRQA): a consensus-based framework for designing, conducting, and reporting
Authors: Kowalski Christine P. , Nevedal Andrea L. , Finley Erin P. , Young Jessica P. , Lewinski Allison A. , Midboe Amanda M. , Hamilton Alison B. 
Published: October 2024

Abstract
Background
The use of rapid qualitative methods has increased substantially over the past decade in quality improvement and health services research. These methods have gained traction in implementation research and practice, wherein real-time adjustments are often made to optimize processes and outcomes. This brisk increase begs the questions: what does rigor entail in projects that use rapid qualitative analysis (RQA)? How do we define a pragmatic framework to help research teams design and conduct rigorous and valid rapid qualitative projects? How can authors articulate rigor in their methods descriptions? Lastly, how can reviewers evaluate the rigor of rapid qualitative projects?.

Methods
A team of seven interdisciplinary qualitative methods experts developed a framework for ensuring rigor and validity in RQA and methods suitable for this analytic approach. We conducted a qualitative evidence synthesis to identify gaps in the literature and then drew upon literature, standard procedures within our teams, and a repository of rapid qualitative training materials to create a planning and reporting framework. We iteratively refined this framework through 11 group working meetings (60-90 minutes each) over the course of one year and invited feedback on items to ensure their completeness, clarity, and comprehensibility.

Results
The Planning for and Assessing Rigor in Rapid Qualitative Analysis (PARRQA) framework is organized progressively across phases from design to dissemination, as follows: 1) rigorous design (rationale and staffing), 2) semi-structured data collection (pilot and planning), 3) RQA: summary template development (accuracy and calibration), 4) RQA: matrix analysis (matrices), and 5) rapid qualitative data synthesis. Eighteen recommendations across these sections specify best practices for rigor and validity.

Conclusions
Rapid qualitative methods play a central role in implementation evaluations, with the potential to yield prompt information and insights about context, processes, and relationships. However, guidance on how to assess rigor is nascent. The PARRQA framework enhances the literature by offering criteria to ensure appropriate planning for and assessment of rigor in projects that involve RQA. This framework provides a consensus-based resource to support high-level qualitative methodological rigor in implementation science.