bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bronchial gene expression alterations associated with radiological bronchiectasis
Authors: Xu Ke , Diaz Alejandro A. , Duan Fenghai , Lee Minyi , Xiao Xiaohui , Liu Hanqiao , Liu Gang , Cho Michael H. , Gower Adam C. , Alekseyev Yuriy O. , Spira Avrum , Aberle Denise R. , Washko George R. , Billatos Ehab , Lenburg Marc E. 
Published: October 2022

ObjectivesDiscovering airway gene expression alterations associated with radiological bronchiectasis may improve the understanding of the pathobiology of early-stage bronchiectasis.MethodsPresence of radiological bronchiectasis in 173 individuals without a clinical diagnosis of bronchiectasis was evaluated. Bronchial brushings from these individuals were transcriptomically profiled and analysed. Single-cell deconvolution was performed to estimate changes in cellular landscape that may be associated with early disease progression.Results20 participants have widespread radiological bronchiectasis (three or more lobes). Transcriptomic analysis reflects biological processes associated with bronchiectasis including decreased expression of genes involved in cell adhesion and increased expression of genes involved in inflammatory pathways (655 genes, false discovery rate <0.1, log2fold-change >0.25). Deconvolution analysis suggests that radiological bronchiectasis is associated with an increased proportion of ciliated and deuterosomal cells, and a decreased proportion of basal cells. Gene expression patterns separated participants into three clusters: normal, intermediate and bronchiectatic. The bronchiectatic cluster was enriched by participants with more lobes of radiological bronchiectasis (p<0.0001), more symptoms (p=0.002), higher SERPINA1 mutation rates (p=0.03) and higher computed tomography derived bronchiectasis scores (p<0.0001).ConclusionsGenes involved in cell adhesion, Wnt signalling, ciliogenesis and interferon-γ pathways had altered expression in the bronchus of participants with widespread radiological bronchiectasis, possibly associated with decreased basal and increased ciliated cells. This gene expression pattern is not only highly enriched among individuals with radiological bronchiectasis, but also associated with airway-related symptoms in those without discernible radiological bronchiectasis, suggesting that it reflects a bronchiectasis-associated, but non-bronchiectasis-specific lung pathophysiological process.
In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
Authors: Chanderraj Rishi , Baker Jennifer M. , Kay Stephen G. , Brown Christopher A. , Hinkle Kevin J. , Fergle Daniel J. , McDonald Roderick A. , Falkowski Nicole R. , Metcalf Joseph D. , Kaye Keith S. , Woods Robert J. , Prescott Hallie C. , Sjoding Michael W. , Dickson Robert P. 
Published: October 2022

BackgroundCritically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. However, in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure and mortality. We therefore designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients.MethodsWe conducted a retrospective single-centre cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. We compared intensive care unit outcomes (ventilator-associated pneumonia (VAP)-free survival, infection-free survival and overall survival) in all patients and changes in gut microbiota in a subcohort of 116 patients. In murine models, we studied the effects of anaerobe depletion in infectious (Klebsiella pneumoniaeandStaphylococcus aureuspneumonia) and noninfectious (hyperoxia) injury models.ResultsEarly administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival (hazard ratio (HR) 1.24, 95% CI 1.06–1.45), infection-free survival (HR 1.22, 95% CI 1.09–1.38) and overall survival (HR 1.14, 95% CI 1.02–1.28). Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalisation (p=0.011) and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic-treated patients (p<2.2×10−16). In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002).ConclusionsIn critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered.
Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis
Authors: Jaffar Jade , Wong Mae , Fishbein Gregory A. , Alhamdoosh Monther , McMillan Laura , Gamell-Fulla Cristina , Ng Milica , Wilson Nick , Symons Karen , Glaspole Ian , Westall Glen 
Published: October 2022

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressively fibrotic lung condition with poor prognosis. Matrix metalloproteinase-7 (MMP7) is a protein secreted by epithelial cells in IPF lungs. It is not known if MMP7 expression correlates with fibrotic changes in lung tissue.MethodsTissue samples from lung apices and bases were obtained from 20 IPF patients and 14 non-diseased control (NDC) donors. In formalin-fixed paraffin-embedded sections, histological assessment of fibrosis was performed; overall MMP7 positivity was assessed by immunohistochemistry and MMP7+cells were quantified using multiplex immunohistochemistry. Protein expression of MMP7 in whole lung lysates was quantified by Western blotting. Bulk tissue transcriptomic profiles of 101 samples were analysed using RNA sequencing technologies.ResultsLung tissue from IPF bases was more fibrotic than in apices. MMP7 protein is elevated in IPF lung base tissue. In IPF whole lung lysates, MMP7 protein levels are increased compared to NDC donors and was increased in IPF lung bases compared to apices. MMP7 protein levels correlated with MMP7 gene expression levels in lung tissue. MMP7 transcript levels were increased in IPF base compared to NDC base lung tissue and increased in IPF base tissue compared to IPF apex tissue.ConclusionsOur cross-sectional study suggests that lung epithelial MMP7 expression increases as the tissue becomes more fibrotic and identifies a potentially nonepithelial or immune-cell source. Mechanisms of disease progression in IPF are still unclear, and our study suggests aberrant MMP7 production may be a histological starting point of lung tissue fibrosis.
The trajectory of COVID-19 cardiopulmonary disease: insights from an autopsy study of community-based, pre-hospital deaths
Authors: Milross Luke , Majo Joaquim , Pulle Julian , Hoggard Sam , Cooper Nigel , Hunter Bethany , Duncan Christopher J.A. , Filby Andrew , Fisher Andrew J. 
Published: October 2022

BackgroundPost mortemexamination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology; however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions.MethodsIn this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy.ResultsThe cohort comprised 22 females and 24 males, median age 64 years (range 19–91) at time of death with illness duration range 0–23 days. Comorbidities associated with poor outcomes in COVID-19 included obesity (body mass index >30 kg·m−2) in 19 out of 46 cases (41.3%). Diffuse alveolar damage in its early exudative phase was the most common pattern of lung injury; however significant heterogeneity was identified with bronchopneumonia, pulmonary oedema consistent with acute cardiac failure, pulmonary thromboembolism and microthrombosis also identified and often in overlapping patterns. Review of clinical records and next of kin accounts suggested a combination of unexpectedly low symptom burden, rapidly progressive disease and psychosocial factors may have contributed to a failure of hospital presentation prior to death.ConclusionsIdentifying such advanced acute lung injury in community-based deaths is extremely unusual and raises the question why some with severe COVID-19 pneumonitis were not hospitalised. Multiple factors including low symptom burden, rapidly progressive disease trajectories and psychosocial factors provide possible explanations.
Inspiratory muscle strength and function in mechanically ventilated COVID-19 survivors 3 and 6 months after intensive care unit discharge
Authors: Núñez-Seisdedos Maria Natividad , Valcárcel-Linares David , Gómez-González María Teresa , Lázaro-Navas Irene , López-González Luís , Pecos-Martín Daniel , Rodríguez-Costa Isabel 
Published: October 2022

BackgroundKnowledge regarding the long-term impact of invasive mechanical ventilation on the inspiratory muscles and functional outcomes in COVID-19 survivors is limited.MethodsIn this single-centre prospective cohort study, we evaluated invasively ventilated patients with COVID-19 pneumonia 3 and 6 months post-intensive care unit (ICU) discharge. Outcomes included: maximal inspiratory pressure (MIP), ultrasound parameters for diaphragm function, 6-min walk distance (6MWD), dyspnoea and quality of life. We evaluated associations between MIP and duration of mechanical ventilation with follow-up outcomes.Results50 COVID-19 survivors discharged from ICU between 15 October 2020 and 1 April 2021 were enrolled. Overall, survivors showed a recovery trajectory over time. However, impaired MIP remained in 24 (48%) and 12 (24%) at 3 and 6 months, respectively. Diaphragm dysfunction was not observed. At 3 months, 23 (46%) had impaired functional capacityversus10 (20%) at 6 months. Dyspnoea persisted in 44 (88%) patients at 3 months and 38 (76%) at 6 months. Quality of life was slightly decreased at 3 months with further improvements at 6 months. MIP was correlated to 6MWD, 6MWD % predicted, dyspnoea across follow-up, and quality of life at 3 months. The duration of invasive ventilation was correlated with 6MWD and 6MWD % predicted.ConclusionIn invasively ventilated COVID-19 survivors, inspiratory muscle strength impairments persisted 6 months after ICU discharge, while maintaining normal diaphragm function. Decreased functional capacity, dyspnoea and slightly reduced health status were observed. Early screening of survivors is of utmost importance to identify those with impairments and at risk of delayed or incomplete recovery.
Unravelling young COPD and pre-COPD in the general population
Authors: Cosío Borja G. , Casanova Ciro , Soler-Cataluña Juan José , Soriano Joan B. , García-Río Francisco , de Lucas Pilar , Alfageme Inmaculada , Rodríguez González-Moro José Miguel , Sánchez Guadalupe , Ancochea Julio , Miravitlles Marc 
Published: October 2022

BackgroundChronic obstructive pulmonary disease (COPD) is commonly diagnosed when the airflow limitation is well established and symptomatic. We aimed to identify individuals at risk of developing COPD according to the concept of pre-COPD and compare their clinical characteristics with 1) those who have developed the disease at a young age, and 2) the overall population with and without COPD.MethodsThe EPISCAN II study is a cross-sectional, population-based study that aims to investigate the prevalence of COPD in Spain in subjects ≥40 years of age. Pre-COPD was defined as the presence of emphysema >5% and/or bronchial thickening by computed chromatography (CT) scan and/or diffusing capacity of the lung for carbon monoxide (DLCO) <80% of predicted in subjects with respiratory symptoms and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) >0.70. Young COPD was defined as FEV1/FVC <0.70 in a subject ≤50 years of age. Demographic and clinical characteristics were compared among pre-COPD, young COPD and the overall population with and without COPD.ResultsAmong the 1077 individuals with FEV1/FVC <0.70, 65 (6.0%) were ≤50 years of age. Among the 8015 individuals with FEV1/FVC >0.70, 350 underwent bothDLCOtesting and chest CT scanning. Of those, 78 (22.3%) subjects fulfilled the definition of pre-COPD. Subjects with pre-COPD were older, predominantly women, less frequently active or ex-smokers, with less frequent previous diagnosis of asthma but with higher symptomatic burden than those with young COPD.Conclusions22.3% of the studied population was at risk of developing COPD, with similar symptomatic and structural changes to those with well-established disease without airflow obstruction. This COPD at-risk population is different from those that develop COPD at a young age.
What is the efficacy of aerobic exercise versus strength training in the treatment of migraine? A systematic review and network meta-analysis of clinical trials
Authors: Woldeamanuel Yohannes W. , Oliveira Arão B. D. 
Published: October 2022

Abstract
Background
Multiple clinical trials with different exercise protocols have demonstrated efficacy in the management of migraine. However, there is no head-to-head comparison of efficacy between the different exercise interventions.

Methods
A systematic review and network meta-analysis was performed involving all clinical trials which determined the efficacy of exercise interventions in reducing the frequency of monthly migraine. Medical journal search engines included Web of Science, PubMed, and Scopus spanning all previous years up to July 30, 2022. Both aerobic and strength/resistance training protocols were included. The mean difference (MD, 95% confidence interval) in monthly migraine frequency from baseline to end-of-intervention between the active and control arms was used as an outcome measure. Efficacy evidence from direct and indirect comparisons was combined by conducting a random effects model network meta-analysis. The efficacy of the three exercise protocols was compared, i.e., moderate-intensity aerobic exercise, high-intensity aerobic exercise, and strength/resistance training. Studies that compared the efficacy of migraine medications (topiramate, amitriptyline) to exercise were included. Additionally, the risk of bias in all included studies was assessed by using the Cochrane Risk of Bias version 2 (RoB2).

Results
There were 21 published clinical trials that involved a total of 1195 migraine patients with a mean age of 35 years and a female-to-male ratio of 6.7. There were 27 pairwise comparisons and 8 indirect comparisons. The rank of the interventions was as follows: strength training (MD = -3.55 [− 6.15, − 0.95]), high-intensity aerobic exercise (-3.13 [-5.28, -0.97]), moderate-intensity aerobic exercise (-2.18 [-3.25, -1.11]), topiramate (-0.98 [-4.16, 2.20]), placebo, amitriptyline (3.82 [− 1.03, 8.68]). The RoB2 assessment showed that 85% of the included studies demonstrated low risk of bias, while 15% indicated high risk of bias for intention-to-treat analysis. Sources of high risk of bias include randomization process and handling of missing outcome data.

Conclusion
Strength training exercise regimens demonstrated the highest efficacy in reducing migraine burden, followed by high-intensity aerobic exercise.
Retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery stenosis
Authors: Liu Junfeng , Wan Jincheng , Kwapong William Robert , Tao Wendan , Ye Chen , Liu Ming , Wu Bo 
Published: October 2022

Abstract
Purpose
To investigate the relationship between retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery (ICA) stenosis.

Methods
Patients with unilateral moderate or severe ICA stenosis(≥50%) from West China hospital, Sichuan university were consecutively and prospectively recruited enrolled in the current study. En face angiograms of the superficial vascular complex (SVC), deep vascular complex (DVC), superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were generated by automatic segmentation using swept-source optical coherence tomography angiography (SS-OCTA) to assess the retinal microvascular perfusion. The cerebral blood flow perfusion on bilateral middle cerebral artery territories measured at the basal ganglia level was assessed by brain computed tomography perfusion (CTP). CTP data were postprocessed to generate maps of different perfusion parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and permeability surface(PS). Relative perfusion parameters (rPS, rCBF, etc.) were calculated as the ratio of the value on the contralateral side to that on the ipsilateral side.

Results
In the final analysis, 31 patients were included, of whom 11 patients had a moderate ICA stenosis (50–69%) and 20 with a severe ICA stenosis(≥70%). A total of 55 eyes were analyzed in the study, 27 eyes from the ipsilateral side (ie, side with stenosis) and 28 eyes from the contralateral side. In the patients with ICA stenosis, there was a strong correlation between the retinal microvascular perfusion of SVC with rCBV(B = 0.45, p = 0.03), rCBF(B = 0.26, p = 0.02) and rPS(B = 0.45, p < 0.001) after adjustment for age, sex and vascular risk factors. Similar correlations were also found between microvasculature in SVP and cerebral perfusion changes. There were no any significant associations of microvascular perfusion in both DVC and DCP with CTP parameters(all p > 0.05).

Conclusions
Retinal perfusion changes in superficial vascular layer (SVC and SVP) were correlated with brain hemodynamic compromise in patients with unilateral moderate or severe ICA stenosis(≥50%). Given the limited size of our study, future studies with larger sample size are needed to confirm our findings.
Screening for novel risk factors related to high myopia using machine learning
Authors: Zhang Ruiheng , Dong Li , Yang Qiong , Zhou Wenda , Wu Haotian , Li Yifan , Li Heyan , Wei Wenbin 
Published: October 2022

Abstract
Background
High myopia-related complications have become a major cause of irreversible vision loss. Evaluating the association between potential factors and high myopia can provide insights into pathophysiologic mechanisms and further intervention targets for myopia progression.

Method
Participants aged 12–25 years from National Health and Nutrition Examination Survey 2001–2006 were selected for the analysis. Myopia was defined as spherical equivalent (sum of spherical error and half of the cylindrical error) of any eyes ≤-0.5 diopters. High myopia was defined as the spherical equivalent of any eye ≤ − 5.00 diopters. Essential variables were selected by Random Forest algorithm and verified by multivariable logistic regression.

Results
A total of 7,033 participants and 74 potential factors, including demographic (4 factors), physical examination (6 factors), nutritional and serological (45 factors), immunological (9 variables), and past medical history factors (10 factors), were included into the analysis. Random Forest algorithm found that several anthropometric, nutritional, and serological factors were associated with high myopia. Combined with multivariable logistic regression, high levels of serum vitamin A was significantly associated with an increased prevalence of high myopia (adjusted odd ratio = 1.46 for 1 µmol/L increment, 95% confidence interval [CI] 1.01–2.10). Furthermore, we found that neither C-reactive protein nor asthma increased the risk and severity of myopia.

Conclusion
High levels of serum vitamin A was seemingly associated with an increased prevalence of high myopia. This borderline significant association should be interpreted with caution because the potential increased type I error after the multiple testing. It still needs further investigation regarding the mechanism underlying this association. Neither C-reactive protein nor asthma increased the risk and severity of myopia.
Social inequalities in women exposed to obstetric and gyneco-obstetric violence in Ecuador: a cross-sectional study
Authors: Arias Fuentes Fara Faith , Arteaga Erika , San Sebastián Miguel 
Published: October 2022

Abstract
Background
Obstetric and gyneco-obstetric violence (OV, GOV) is a concerning public health problem, particularly in Latin America. This study aimed to determine the prevalence of OV and GOV and to assess its socio-geographical distribution in Ecuador.

Methods
This cross-sectional study used data from a national survey conducted in 2019 (n = 17,211) among women aged 15 years and over. Independent variables included age, marital status, education, ethnicity, place of residence and region. The chosen outcomes were lifetime experience of OV and GOV. Frequency tables were calculated and crude and adjusted regression models estimating prevalence ratios and their 95% confidence intervals were computed.

Results
Nearly one-third (32.8%) of the participants had experienced OV and two-fifths (41.86%) GOV at least once in their lifetime. Prevalence of OV were particularly common in women 26–35 and 46–55 years old, with primary or middle education and in urban regions. In comparison, GOV had a higher prevalence in women aged > 65 years and with no formal education. Both subtypes of violence were more common among women with current or earlier partners compared with the single ones. Also the two outcomes were more prevalent in the non-white population, OV among the populations of colour (POC), while GOV both, in the POC and Indigenous group. Additionally, women from the Highlands and Amazon reported higher OV and GOV than the Coastal group.

Conclusion
Our study showed that OV and GOV are common in Ecuador and identified an unequal distribution of their prevalence across different socio-geographical groups. Further studies including more social factors and a continuous monitoring of OV and GOV are recommended. Current policies, laws to protect women and guidelines regarding the treatment of women, particularly in health care settings, need to be constantly advocated for and effectively implemented in the country.