bluuebunny/crossref_metadata_2025_split huggingface dataset:
Know diabetes by heart: Education about the linkage between cardiovascular disease and diabetes
Authors: Parisi Michelle , McFall Danielle , Ankomah Samuel , Dietz Christina J , Kanny Samantha , Jones Kadalynn Grace , Stancil Michelle , Sherrill Windsor Westbrook 
Published: December 2022

Objective: The objective of this study was to investigate how a 1-hour education session that highlights American Heart Association/American Diabetes Association’s Know Diabetes by Heart (KDBH) messaging changed the knowledge and behavioural intention of participants. Design: Single group, quasi-experimental study evaluating the impact of the KDBH education intervention on participants’ knowledge and intentions to engage in risk-lowering behaviours related to the link between diabetes and cardiovascular disease. Setting: A free, 1-hour, synchronously delivered education session was offered through an online platform and facilitated by Cooperative Extension agents. Methods: A pre- and post-Qualtrics survey was used to assess changes in knowledge and intended behaviours. Slides were provided by the American Diabetes Association and tailored for clarification and evaluation purposes. Results: The study included 259 adults with an average age of 54 years (standard deviation [ SD] = 16.67) and 72.97% being 46 years or older. When participants were asked if having type 2 diabetes put them at risk for development of hypertension, unhealthy cholesterol levels, heart attack, or stroke, 84.84% answered correctly at baseline. After session completion, the percentage correct increased to 92.2% ( p = .002). Individual’s knowledge of cardiovascular disease as the leading cause of death for people with type 2 diabetes was assessed; 66.80% answered correctly pre-intervention. After completing the KDBH programme, 95.37% answered correctly ( p = .001). In addition, more than half of those with type 2 diabetes reported intended to adopt several behaviours related to reducing the risk of cardiovascular disease at the completion of the programme. Conclusions: The pilot study indicates successful information transfer in a 1-hour education session focused on chronic disease risks associated with T2DM. Results support the use of synchronous online platforms for diabetes and heart disease information transfer. Future prospective studies measuring sustained knowledge, behaviour adoption and incidence of heart-disease before and after education are needed.
Interstitial lung disease progression after genomic usual interstitial pneumonia testing
Authors: Chaudhary Sachin , Weigt S. Sam , Ribeiro Neto Manuel L. , Benn Bryan S. , Pugashetti Janelle Vu , Keith Rebecca , Chand Arista , Oh Scott , Kheir Fayez , Ramalingam Vijaya , Solomon Joshua J. , Harper Richart , Lasky Joseph A. , Oldham Justin M. 
Published: December 2022

BackgroundA genomic classifier for usual interstitial pneumonia (gUIP) has been shown to predict histological UIP with high specificity, increasing diagnostic confidence for idiopathic pulmonary fibrosis (IPF). Whether those with positive gUIP classification exhibit a progressive, IPF-like phenotype remains unknown.MethodsA pooled, retrospective analysis of patients who underwent clinically indicated diagnostic bronchoscopy with gUIP testing at seven academic medical centres across the USA was performed. We assessed the association between gUIP classification and 18-month progression-free survival (PFS) using Cox proportional hazards regression. PFS was defined as the time from gUIP testing to death from any cause, lung transplant, ≥10% relative decline in forced vital capacity (FVC) or censoring at the time of last available FVC measure. Longitudinal change in FVC was then compared between gUIP classification groups using a joint regression model.ResultsOf 238 consecutive patients who underwent gUIP testing, 192 had available follow-up data and were included in the analysis, including 104 with positive gUIP classification and 88 with negative classification. In multivariable analysis, positive gUIP classification was associated with reduced PFS (hazard ratio 1.58, 95% CI 0.86–2.92; p=0.14), but this did not reach statistical significance. Mean annual change in FVC was −101.8 mL (95% CI −142.7– −60.9 mL; p<0.001) for those with positive gUIP classification and −73.2 mL (95% CI −115.2– −31.1 mL; p<0.001) for those with negative classification (difference 28.7 mL, 95% CI −83.2–25.9 mL; p=0.30).ConclusionsgUIP classification was not associated with differential rates of PFS or longitudinal FVC decline in a multicentre interstitial lung disease cohort undergoing bronchoscopy as part of the diagnostic evaluation.
The effect of exacerbations on lung density in α1-antitrypsin deficiency
Authors: Strange Charlie , McElvaney N. Gerard , Vogelmeier Claus F. , Marin-Galiano Marcos , Buch-Haensel Michaela , Zhang Xiang , Chen Younan , Vit Oliver , Wencker Marion , Chapman Kenneth R. 
Published: December 2022

BackgroundAcute exacerbations of COPD (AECOPD) have unclear impacts on emphysema measurement using computed tomography (CT)-derived 15th percentile lung density (PD15). The aim of this study was to assess the influence of AECOPD on PD15 lung density in α1-antitrypsin deficiency.MethodsIn apost hocanalysisof the RAPID (Randomised Trial of Augmentation Therapy in α1-Proteinase Inhibitor Deficiency) trial, raw marginal residuals of PD15 (measured − predicted) were determined by fitting a regression line to individual patient CT data. These deviations from the expected slope were compared by age, sex, baseline forced expiratory volume in 1 s, diffusing capacity of the lungs for carbon monoxide % predicted and PD15, inhaled corticosteroid use and treatment group.ResultsPositive and negative residuals (reflecting higher or lower lung density than predicted from regression) were observed, which declined in magnitude over time following AECOPD events. Logistic regression confirmed a limited effect of patient characteristics on the absolute size of residuals, whereas AECOPD within 6 weeks of CT had a notable effectversusno AECOPD within 6 weeks (OR 5.707, 95% CI 3.375–9.652; p<0.0001).ConclusionAECOPD result in higher or lower CT lung density estimates; the effect is greatest in the 2 weeks immediately after an AECOPD and persists for <6 weeks. Patient characteristics were less relevant than AECOPD within 6 weeks, supporting the reliability of PD15 as a measure of lung density. An exacerbation-free period prior to CT scan is advisable to reduce signal-to-noise ratio in future clinical trials.
High-throughput functional assay in cystic fibrosis patient-derived organoids allows drug repurposing
Authors: Spelier Sacha , de Poel Eyleen , Ithakisiou Georgia N. , Suen Sylvia W.F. , Hagemeijer Marne C. , Muilwijk Danya , Vonk Annelotte M. , Brunsveld Jesse E. , Kruisselbrink Evelien , van der Ent Cornelis K. , Beekman Jeffrey M. 
Published: December 2022

BackgroundCystic fibrosis (CF) is a rare hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recent therapies enable effective restoration of CFTR function of the most common F508delCFTRmutation. This shifts the unmet clinical need towards people with rareCFTRmutations such as nonsense mutations, of which G542X and W1282X are most prevalent. CFTR function measurements in patient-derived cell-based assays played a critical role in preclinical drug development for CF and may play an important role to identify new drugs for people with rareCFTRmutations.MethodsHere, we miniaturised the previously described forskolin-induced swelling (FIS) assay in intestinal organoids from a 96-well to a 384-well plate screening format. Using this novel assay, we tested CFTR increasing potential of a 1400-compound Food and Drug Administration (FDA)-approved drug library in organoids from donors with W1282X/W1282XCFTRnonsense mutations.ResultsThe 384-well FIS assay demonstrated uniformity and robustness based on coefficient of variation and Z’-factor calculations. In the primary screen, CFTR induction was limited overall, yet interestingly, the top five compound combinations that increased CFTR function all contained at least one statin. In the secondary screen, we indeed verified that four out of the five statins (mevastatin, lovastatin, simvastatin and fluvastatin) increased CFTR function when combined with CFTR modulators. Statin-induced CFTR rescue was concentration-dependent and W1282X-specific.ConclusionsFuture studies should focus on elucidating genotype specificity and mode-of-action of statins in more detail. This study exemplifies proof of principle of large-scale compound screening in a functional assay using patient-derived organoids.
Pulmonary arterial compliance and exercise capacity after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension
Authors: Sermet Romain , Piliero Nicolas , Guillien Alicia , Madoun Simon , Doutreleau Stéphane , Salvat Muriel , Finas Mathieu , Thony Frédéric , Vautrin Estelle , Bouvaist Hélène , Degano Bruno 
Published: December 2022

ObjectiveTo determine whether changes in pulmonary vascular resistance (PVR) and changes in pulmonary artery compliance (Cpa) are associated with changes in exercise capacity assessed either by changes in peak oxygen consumption (V′O2) or by changes in 6-min walk distance (6MWD) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA).MethodsInvasive haemodynamic parameters, peakV′O2and 6MWD were measured within 24 h, before and after BPA (interval 3.1±2.4 months) in 34 CTEPH patients without significant cardiac and/or pulmonary comorbidities, of whom 24 received at least one pulmonary hypertension-specific treatment.Cpawas calculated according to the pulse pressure method:Cpa=((SV/PP)/1.76+0.1), where SV is the stroke volume and PP is the pulse pressure. The resistance–compliance (RC)-time of the pulmonary circulation was calculated as the PVR andCpaproduct.ResultsAfter BPA, PVR decreased (562±234versus290±106 dyn·s·cm−5; p<0.001);Cpaincreased (0.90±0.36versus1.63±0.65 mL·mmHg−1; p<0.001); but RC-time did not change (0.325±0.069versus0.321±0.083 s; p=0.75). There were improvements in peakV′O2(1.11±0.35versus1.30±0.33 L·min−1; p<0.001) and in 6MWD (393±119versus432±100 m; p<0.001). After adjustment for age, height, weight and gender, changes in exercise capacity, assessed either by peakV′O2or 6MWD, were significantly associated with changes in PVR, but not with changes inCpa.ConclusionsContrary to what has been reported in CTEPH patients undergoing pulmonary endarterectomy, in CTEPH patients undergoing BPA, changes in exercise capacity were not associated with changes inCpa.
Nebulised interferon-β1a (SNG001) in hospitalised COVID-19: SPRINTER phase III study
Authors: Monk Phillip D. , Brookes Jody L. , Tear Victoria J. , Batten Toby N. , Mankowski Marcin , Adzic-Vukicevic Tatjana , Crooks Michael G. , Dosanjh Davinder P.S. , Kraft Monica , Brightling Christopher E. , Gabbay Felicity J. , Holgate Stephen T. , Djukanovic Ratko , Wilkinson Tom M.A. 
Published: December 2022

BackgroundDespite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-β is a naturally occurring protein that stimulates host immune responses against most viruses, including severe acute respiratory syndrome coronavirus 2. SNG001 is a recombinant IFN-β1a formulation delivered to the lungsvianebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygenvianasal prongs or mask.MethodsPatients were randomised double-blind to SNG001 (n=309) or placebo (n=314) once daily for 14 days plus standard of care (SoC). The primary objective was to evaluate recovery after administration of SNG001versusplacebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary end-points were progression to severe disease or death, progression to intubation or death and death.ResultsMedian time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio (HR) 1.06 (95% CI 0.89–1.27); p=0.51); time to recovery was 25.0 days in both groups (HR 1.02 (95% CI 0.81–1.28); p=0.89). There were no significant SNG001–placebo differences for the key secondary end-points, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively; OR 0.71 (95% CI 0.44–1.15); p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively.ConclusionsAlthough the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary end-points analysis suggested that SNG001 may have prevented progression to severe disease.
Transcriptome analysis and identification of chemosensory genes in the larvae of Plagiodera versicolora
Authors: Wu Zhe-Ran , Fan Jian-Ting , Tong Na , Guo Jin-Meng , Li Yang , Lu Min , Liu Xiao-Long 
Published: December 2022

Abstract
Background
In insects, the chemosensory system is crucial in guiding their behaviors for survival. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. There is little known about the chemosensory genes in P. versicolora. Here, we conducted a transcriptome analysis of larvae heads in P. versicolora.

Results
In this study, 29 odorant binding proteins (OBPs), 6 chemosensory proteins (CSPs), 14 odorant receptors (ORs), 13 gustatory receptors (GRs), 8 ionotropic receptors (IRs) and 4 sensory neuron membrane proteins (SNMPs) were identified by transcriptome analysis. Compared to the previous antennae and foreleg transcriptome data in adults, 12 OBPs, 2 CSPs, 5 ORs, 4 IRs, and 7 GRs were newly identified in the larvae. Phylogenetic analyses were conducted and found a new candidate CO2 receptor (PverGR18) and a new sugar receptor (PverGR23) in the tree of GRs. Subsequently, the dynamic expression profiles of various genes were analyzed by quantitative real-time PCR. The results showed that PverOBP31, OBP34, OBP35, OBP38, and OBP40 were highly expressed in larvae, PverOBP33 and OBP37 were highly expressed in pupae, and PverCSP13 was highly expressed in eggs, respectively.

Conclusions
We identified a total of 74 putative chemosensory genes based on a transcriptome analysis of larvae heads in P. versicolora. This work provides new information for functional studies on the chemoreception mechanism in P. versicolora.
Differential miRNA expression profiles in the bone marrow of Beagle dogs at different stages of Toxocara canis infection
Authors: Gao Jin , Zou Yang , Wu Xiao-Jing , Xu Yue , Zhu Xing-Quan , Zheng Wen-Bin 
Published: December 2022

Abstract
Background
Toxocara canis is distributed worldwide, posing a serious threat to both human and dog health; however, the pathogenesis of T. canis infection in dogs remains unclear. In this study, the changes in microRNA (miRNA) expression profiles in the bone marrow of Beagle dogs were investigated by RNA-seq and bioinformatics analysis.

Results
Thirty-nine differentially expressed (DE) miRNAs (DEmiRNAs) were identified in this study. Among these, four DEmiRNAs were identified at 24 h post-infection (hpi) and all were up-regulated; eight DEmiRNAs were identified with two up-regulated miRNAs and six down-regulated miRNAs at 96 hpi; 27 DEmiRNAs were identified with 13 up-regulated miRNAs and 14 down-regulated miRNAs at 36 days post-infection (dpi). Among these DEmiRNAs, cfa-miR-193b participates in the immune response by regulating the target gene cd22 at 24 hpi. The novel_328 could participate in the inflammatory and immune responses through regulating the target genes tgfb1 and tespa1, enhancing the immune response of the host and inhibiting the infection of T. canis at 96 hpi. In addition, cfa-miR-331 and novel_129 were associated with immune response and self-protection mechanisms at 36 dpi. 20 pathways were significantly enriched by KEGG pathway analysis, most of which were related to inflammatory response, immune response and cell differentiation, such as Cell adhesion molecules (CAMs), ECM-receptor interaction and Focal adhesion.

Conclusions
These findings suggested that miRNAs of Beagle dog bone marrow play important roles in the pathogenesis of T. canis infection in dogs and provided useful resources to better understand the interaction between T. canis and the hosts.
Comparative and phylogenetic analysis based on chloroplast genome of Heteroplexis (Compositae), a protected rare genus
Authors: Duan Na , Deng Lili , Zhang Ying , Shi YanCai , Liu Bingbing 
Published: December 2022

Abstract
Background
Heteroplexis Chang is an endangered genus endemic to China with important ecological and medicinal value. However, due to the lack of genetic data, our conservation strategies have repeatedly been delayed by controversial phylogenetic (molecular) relationships within the genera. In this study, we reported three new Heteroplexis chloroplast (cp.) genomes (H. vernonioides, H. impressinervia and H. microcephala) to clarify phylogenetic relationships between species allocated in this genus and other related Compositae.

Results
All three new cp. genomes were highly conserved, showing the classic four regions. Size ranged from 152,984 − 153,221 bp and contained 130 genes (85 protein-coding genes, 37 tRNA, eight rRNA) and two pseudogenes. By comparative genomic and phylogenetic analyses, we found a large-scale inversion of the entire large single-copy (LSC) region in H. vernonioides, H. impressinervia and H. microcephala, being experimentally verified by PCR. The inverted repeat (IR) regions showed high similarity within the five Heteroplexis plastomes, showing small-size contractions. Phylogenetic analyses did not support the monophyly of Heteroplexis genus, whereas clustered the five species within two differentiated clades within Aster genus. These phylogenetic analyses suggested that the five Heteroplexis species might be subsumed into the Aster genus.

Conclusion
Our results enrich the data on the cp. genomes of the genus Heteroplexis, providing valuable genetic resources for future studies on the taxonomy, phylogeny, and evolution of Aster genus.
Prevalence of frailty among patients with inflammatory bowel disease and its association with clinical outcomes: a systematic review and meta-analysis
Authors: Huang Xiangting , Xiao Mengmeng , Jiang Benyue , Wang Xiuzheng , Tang Xiaoyu , Xu Xiao , Chen Ying , Wang Shixuan , Yan Songbo , Wang Siyi , Wang Jiang , Zhang Pinglan 
Published: December 2022

Abstract
Background
Studies have reported frailty as an independent risk factor of mortality in patients with inflammatory bowel disease (IBD). However, no systematic review and meta-analysis has been conducted to determine the relationship of frailty and IBD. We aimed to investigate the prevalence of frailty in patients with IBD and the impact of frailty on the clinical prognosis of these patients.

Methods
We systematically searched PubMed, Ovid (Medline), Embase, Web of Science, and Cochrane Library from database inception until October 2022. This systematic review included observational studies describing IBD and frailty. We performed meta-analysis for the frailty prevalence in patients with IBD. We analyzed primary outcomes (mortality) and secondary outcomes (infections, hospitalizations, readmission, and IBD-related surgery).

Results
Nine studies with a total of 1,495,695 participants were included in our meta-analysis. The prevalence of frailty was 18% in patients with IBD. The combined effect analysis showed that frail patients with IBD had a higher risk of mortality (adjusted hazard ratio = 2.25, 95% confidence interval: 1.11–4.55) than non-frail patients with IBD. The hazard ratio for infections (HR = 1.23, 0.94–1.60), hospitalizations (HR = 1.72, 0.88–3.36), readmission (HR = 1.21, 1.17–1.25) and IBD-related surgery (HR = 0.78, 0.66–0.91) in frail patients with IBD.

Conclusions
We demonstrated that frailty is a significant independent predictor of mortality in patients with IBD. Our work supports the importance of implementing frailty screening upon admission in patients with IBD. More prospective studies are needed to investigate the influence of frailty on patients with IBD and improve the poor prognosis of patients with frailty and IBD.
A prospective, randomized, phase II study to assess the schemas of retreatment with Lutathera® in patients with new progression of an intestinal, well-differentiated neuroendocrine tumor (ReLUTH)
Authors: Deshayes Emmanuel , Assenat Eric , Meignant Laetitia , Bardiès Manuel , Santoro Lore , Gourgou Sophie 
Published: December 2022

Abstract
Background
Although neuroendocrine tumors (NET) are classed as rare, they have a high prevalence and their incidence is increasing. Effective treatment with lutetium 17-[177Lu]Lu-oxodotreotide (Lutathera®) is possible in patients with well-differentiated NET, improving progression-free survival (PFS), overall survival (OS), and quality of life (QoL). However, progression does occur. Retreatment with additional Lutathera® cycles is an option to extend PFS and OS. Two retreatment cycles are usually proposed. We aim to compare four versus two Lutathera® retreatment cycles in patients with new progression of a well-differentiated intestinal NET.

Methods
This will be a multicenter, randomized, controlled, open-label, phase II study in France (ReLUTH). The aim is to evaluate the efficacy of retreatment with Lutathera® in patients with progressive intestinal NET (determined by somatostatin-receptor positive imaging) after previous treatment with two cycles of Lutathera®. Before randomization, all patients will have already received two Lutathera® retreatment cycles (7.4 GBq infusion each, 8 weeks apart). A total of 146 patients will be randomized (1:1) to two additional cycles of Lutathera® (7.4 GBq infusion each, separated by 8 weeks) or to no treatment (active surveillance). Primary objective: efficacy of two additional Lutathera® retreatment cycles compared to active surveillance over 6 months. Primary endpoint: disease control rate at 6 months from randomization (defined as Complete Response, Partial Response, and Stable Disease in the Response Evaluation Criteria In Solid Tumours) with an evaluation every 2 months. A secondary objective will be the safety, as well as the PFS, OS, and QoL. It is expected that the efficacy of retreatment will increase after two additional Lutathera® cycles, with no increased safety concerns.

Discussion
Our prospective, randomized controlled study may lead to new recommendations for the use of Lutathera® in patients with intestinal progressive NET, and should confirm that four cycles will be more effective than two, with limited adverse impact on safety. Four Lutathera® treatment cycles have the potential to prolong life and improve quality of life in patients.

Trial registration
ClinicalTrials.gov: NCT04954820.