bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased plasma levels of the brain-derived neurotrophic factor correlate with right heart congestion in pulmonary arterial hypertension
Authors: Schäfer Katharina , Tello Khodr , Pak Oleg , Richter Manuel , Gierhardt Mareike , Kwapiszewska Grazyna , Veith Christine , Fink Ludger , Gall Henning , Hecker Matthias , Kojonazarov Baktybek , Kraut Simone , Lo Kevin , Wilhelm Jochen , Grimminger Friedrich , Seeger Werner , Schermuly Ralph T. , Ghofrani Hossein A. , Zahner Daniel , Gerstberger Rüdiger , Weissmann Norbert , Sydykov Akylbek , Sommer Natascha 
Published: January 2023

BackgroundThe brain-derived neurotrophic factor (BDNF) may promote development of pulmonary hypertension and right ventricular (RV) failure. However, BDNF plasma levels were decreased in patients with left ventricular (LV) failure. Therefore, we investigated BDNF plasma levels in pulmonary hypertension patients and the role of BDNF in mouse models of pulmonary hypertension and isolated RV failure.MethodsBDNF plasma levels were correlated to pulmonary hypertension in two patient cohorts, including either post- and pre-capillary pulmonary hypertension patients (first cohort) or only pre-capillary pulmonary hypertension patients (second cohort). In the second cohort, RV dimensions and load-independent function were determined by imaging and pressure–volume catheter measurements, respectively. For induction of isolated RV pressure overload, heterozygousBdnfknockout (Bdnf+/−) mice were subjected to pulmonary arterial banding (PAB). For induction of pulmonary hypertension, mice with inducible knockout of BDNF in smooth muscle cells (Bdnf/Smmhcknockout) were exposed to chronic hypoxia.ResultsPlasma BDNF levels were decreased in patients with pulmonary hypertension. Following adjustment for covariables, BDNF levels negatively correlated in both cohorts with central venous pressure. In the second cohort, BDNF levels additionally negatively correlated with RV dilatation. In animal models, BDNF downregulation attenuated RV dilatation inBdnf+/−mice after PAB or hypoxicBdnf/Smmhcknockout mice, although they developed pulmonary hypertension to a similar extent.ConclusionsSimilar to LV failure, circulating levels of BDNF were decreased in pulmonary hypertension patients, and low BDNF levels were associated with right heart congestion. Decreased BDNF levels did not worsen RV dilatation in animal models, and thus, may be the consequence, but not the cause of RV dilatation.
Cardiovascular disease-linked plasma proteins are mainly associated with lung volume
Authors: Rydell Andreas , Nerpin Elisabet , Zhou XingWu , Lind Lars , Lindberg Eva , Theorell Haglöw Jenny , Fall Tove , Janson Christer , Lisspers Karin , Elmståhl Sölve , Zaigham Suneela , Melander Olle , Nilsson Peter M. , Ärnlöv Johan , Malinovschi Andrei 
Published: January 2023

BackgroundEpidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio.MethodsWe used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort.ResultsPlasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity.ConclusionsFive proteins were associated with both FEV1and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.
Functional imaging in asthma and COPD: design of the NOVELTY ADPro substudy
Authors: Marshall Helen , Wild Jim M. , Smith Laurie J. , Hardaker Latife , Fihn-Wikander Titti , Müllerová Hana , Hughes Rod 
Published: January 2023

The NOVEL observational longiTudinal studY (NOVELTY; ClinicalTrials.gov identifierNCT02760329) is a global, prospective, observational study of ∼12 000 patients with a diagnosis of asthma and/or COPD. Here, we describe the design of the Advanced Diagnostic Profiling (ADPro) substudy of NOVELTY being conducted in a subset of ∼180 patients recruited from two primary care sites in York, UK. ADPro is employing a combination of novel functional imaging and physiological and metabolic modalities to explore structural and functional changes in the lungs, and their association with different phenotypes and endotypes.Patients participating in the ADPro substudy will attend two visits at the University of Sheffield, UK, 12±2 months apart, at which they will undergo imaging and physiological lung function testing. The primary end-points are the distributions of whole lung functional and morphological measurements assessed with xenon-129 magnetic resonance imaging, including ventilation, gas transfer and airway microstructural indices. Physiological assessments of pulmonary function include spirometry, bronchodilator reversibility, static lung volumesviabody plethysmography, transfer factor of the lung for carbon monoxide, multiple-breath nitrogen washout and airway oscillometry. Fractional exhaled nitric oxide will be measured as a marker of type-2 airways inflammation.Regional and global assessment of lung function using these techniques will enable more precise phenotyping of patients with physician-assigned asthma and/or COPD. These techniques will be assessed for their sensitivity to markers of early disease progression.
Management of nontuberculous mycobacteria in lung transplant cases: an international Delphi study
Authors: Asif Huda , Rahaghi Franck F. , Ohsumi Akihiro , Philley Julie , Emtiazjoo Amir , Hirama Takashi , Baker Arthur W. , Shu Chin-Chung , Silveira Fernanda , Poulin Vincent , Rizzuto Pete , Nagao Miki , Burgel Pierre-Régis , Hays Steve , Aksamit Timothy , Kawasaki Takeshi , Dela Cruz Charles , Aliberti Stefano , Nakajima Takahiro , Ruoss Stephen , Marras Theodore K. , Snell Gregory I. , Winthrop Kevin , Mirsaeidi Mehdi 
Published: January 2023

RationaleNontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing onMycobacterium aviumcomplex (MAC),M. abscessusandM. kansasii.MethodsPulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to −5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <−4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated.ResultsPanellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC,M. abscessusorM. kansasii.Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative forM. kansasii, but 12 months of further treatment from the time of culture-negative forM. abscessusbefore listing for LTx.ConclusionThis NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.
Definitions of non-response and response to biological therapy for severe asthma: a systematic review
Authors: Khaleva Ekaterina , Rattu Anna , Brightling Chris , Bush Andrew , Bourdin Arnaud , Bossios Apostolos , Chung Kian Fan , Chaudhuri Rekha , Coleman Courtney , Djukanovic Ratko , Dahlén Sven-Erik , Exley Andrew , Fleming Louise , Fowler Stephen J. , Gupta Atul , Hamelmann Eckard , Koppelman Gerard H. , Melén Erik , Mahler Vera , Seddon Paul , Singer Florian , Porsbjerg Celeste , Ramiconi Valeria , Rusconi Franca , Yasinska Valentyna , Roberts Graham 
Published: January 2023

BackgroundBiologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma.MethodsWe searched four bibliographic databases from inception to 15 March 2021.Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken.Results13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated “very low” to “low” for quality of measurement properties and none met all quality standards.ConclusionsThis is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.
Outcome prediction model and prognostic biomarkers for COVID-19 patients in Vietnam
Authors: Nguyen Hien Thi Thu , Le-Quy Vang , Ho Son Van , Thomsen Jakob Holm Dalsgaard , Pontoppidan Stoico Malene , Tong Hoang Van , Nguyen Nhat-Linh , Krarup Henrik Bygum , Nguyen Son Hong , Tran Viet Quoc , Toan Nguyen Linh , Dinh-Xuan Anh Tuan 
Published: January 2023

BackgroundAccurate prognosis is important either after acute infection or during long-term follow-up of patients infected by severe acute respiratory syndrome coronavirus 2. This study aims to predict coronavirus disease 2019 (COVID-19) severity based on clinical and biological indicators, and to identify biomarkers for prognostic assessment.MethodsWe included 261 Vietnamese COVID-19 patients, who were classified into moderate and severe groups. Disease severity prediction based on biomarkers and clinical parameters was performed by applying machine learning and statistical methods using the combination of clinical and biological data.ResultsThe random forest model could predict with 97% accuracy the likelihood of COVID-19 patients who subsequently worsened to the severe condition. The most important indicators were interleukin (IL)-6, ferritin and D-dimer. The model could still predict with 92% accuracy after removing IL-6 from the analysis to generalise the applicability of the model to hospitals with limited capacity for IL-6 testing. The five most effective indicators were C-reactive protein (CRP), D-dimer, IL-6, ferritin and dyspnoea. Two different sets of biomarkers (D-dimer, IL-6 and ferritin, and CRP, D-dimer and IL-6) are applicable for the assessment of disease severity and prognosis. The two biomarker sets were further tested through machine learning algorithms and relatively validated on two Danish COVID-19 patient groups (n=32 and n=100). The results indicated that various biomarker sets combined with clinical data can be used for detection of the potential to develop the severe condition.ConclusionThis study provided a simple and reliable model using two different sets of biomarkers to assess disease severity and predict clinical outcomes in COVID-19 patients in Vietnam.
Moderate-to-severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality
Authors: Maamar Adel , Guillot Pauline , Joussellin Vincent , Delamaire Flora , Painvin Benoit , Bichon Anaëlle , de la Jartre Océane Bernard , Mauget Matteo , Lesouhaitier Mathieu , Tadié Jean Marc , Terzi Nicolas , Gacouin Arnaud 
Published: January 2023

BackgroundThis study aimed to compare ventilatory parameters recorded in the first days of acute respiratory distress syndrome (ARDS) and mortality at day 60 between coronavirus disease 2019 (COVID-19) and influenza ARDS patients with arterial oxygen tension (PaO2)/inspiratory oxygen fraction (FIO2) ≤150 mmHg.MethodsWe compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure, respiratory system compliance (Crs), ventilator ratio, corrected minute ventilation (V′Ecorr) and surrogate of mechanical power (index=(4×driving pressure)+respiratory rate) were calculated from day 1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed.ResultsOn day 1 of ARDS, COVID-19 patients had significantly higherPaO2/FIO2(median (interquartile range) 97 (79–129.2)versus83 (62.2–114) mmHg; p=0.001), and lower driving pressure (13.0 (11.0–16.0)versus14.0 (12.0–16.7) cmH2O; p=0.01), ventilatory ratio (2.08 (1.73–2.49versus2.52 (1.97–3.03); p<0.001),V′Ecorr(12.7 (10.2–14.9)versus14.9 (11.6–18.6) L·min−1; p<0.001) and index (80 (70–89)versus84 (75–94); p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5, repeated values ofPaO2/FIO2, arterial carbon dioxide tension, ventilatory ratio andV′Ecorrdiffered significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29%versus21.7%; p=0.43).ConclusionsVentilation was more impaired in influenza than in COVID-19 ARDS patients on the first day of ARDS with an important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.
Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis
Authors: Gudmundsson Eyjolfur , Zhao An , Mogulkoc Nesrin , van Beek Frouke , Goos Tinne , Brereton Christopher J. , Veltkamp Marcel , Chapman Robert , van Es Hendrik W. , Garthwaite Helen , Gholipour Bahareh , Heightman Melissa , Nair Arjun , Pontoppidan Katarina , Savas Recep , Ahmed Asia , Vermant Marie , Unat Omer , Procter Alex , De Sadeleer Laurens , Denneny Emma , Wallis Timothy , Duncan Mark , Taylor Magali , Verleden Stijn , Janes Sam M. , Alexander Daniel C. , Wells Athol U. , Porter Joanna , Jones Mark G. , Stewart Iain , van Moorsel Coline H.M. , Wuyts Wim , Jacob Joseph 
Published: January 2023

BackgroundComputer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP).MethodsTwo CT scans 6–36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change.ResultsΔ-PPFE associated weakly with ILD and FVC change. 22–26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16–1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00–1.35, p=0.045).InterpretationProgression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.
Transcriptomics and co-expression network analysis revealing candidate genes for the laccase activity of Trametes gibbosa
Authors: Chen Jie , Ye Yi , Chi Yujie , Hao Xin , Zhao Qingquan 
Published: January 2023

Abstract
Background
Trametes gibbosa, which is a white-rot fungus of the Polyporaceae family found in the cold temperate zone, causes spongy white rot on wood. Laccase can oxidize benzene homologs and is one of the important oxidases for white rot fungi to degrade wood. However, the pathway of laccase synthesis in white rot fungi is unknown.

Results
The peak value of laccase activity reached 135.75 U/min/L on the 9th day. For laccase activity and RNA-seq data, gene expression was segmented into 24 modules. Turquoise and blue modules had greater associations with laccase activity (positively 0.94 and negatively -0.86, respectively). For biology function, these genes were concentrated on the cell cycle, citrate cycle, nicotinate, and nicotinamide metabolism, succinate dehydrogenase activity, flavin adenine dinucleotide binding, and oxidoreductase activity which are highly related to the laccase synthetic pathway. Among them, gene_8826 (MW199767), gene_7458 (MW199766), gene_61 (MW199765), gene_1741 (MH257605), and gene_11087 (MK805159) were identified as central genes.

Conclusion
Laccase activity steadily increased in wood degradation. Laccase oxidation consumes oxygen to produce hydrogen ions and water during the degradation of wood. Some of the hydrogen ions produced can be combined by Flavin adenine dinucleotide (FAD) to form reduced Flavin dinucleotide (FADH2), which can be transmitted. Also, the fungus was starved of oxygen throughout fermentation, and the NADH and FADH2 are unable to transfer hydrogen under hypoxia, resulting in the inability of NAD and FAD to regenerate and inhibit the tricarboxylic acid cycle of cells. These key hub genes related to laccase activity play important roles in the molecular mechanisms of laccase synthesis for exploring industrial excellent strains.
Age-adjusted Charlson Comorbidity Index as effective predictor for in-hospital mortality of patients with cardiac arrest: a retrospective study
Authors: Zhang Nan , Lin Qingting , Jiang Hui , Zhu Huadong 
Published: January 2023

Abstract
Background

Cardiac arrest is currently one of the leading causes of mortality in clinical practice, and the Charlson Comorbidity Index (CCI) is widely utilized to assess the severity of comorbidities. We aimed to evaluate the relationship between the age-adjusted CCI score and in-hospital mortality in intensive care unit (ICU) patients with the diagnosis of cardiac arrest, which is important but less explored previously.

Methods
This was a retrospective study including patients aged over 18 years from the MIMIC-IV database. We calculated the age-adjusted CCI using age information and ICD codes. The univariate analysis for varied predictors’ differences between the survival and the non-survival groups was performed. In addition, a multiple factor analysis was conducted based on logistic regression analysis with the primary result set as hospitalization death. An additional multivariate regression analysis was conducted to estimate the influence of hospital and ICU stay.

Results
A total of 1772 patients were included in our study, with median age of 66, among which 705 (39.8%) were female. Amongst these patients, 963 (54.3%) died during the hospitalization period. Patients with higher age-adjusted CCI scores had a higher likelihood of dying during hospitalization (P < 0.001; OR: 1.109; 95% CI: 1.068–1.151). With the age-adjusted CCI incorporated into the predictive model, the area under the receiver operating characteristic curve was 0.794 (CI: 0.773–0.814), showing that the prediction model is effective. Additionally, patients with higher age-adjusted CCI scores stayed longer in the hospital (P = 0.026, 95% CI: 0.056–0.896), but there was no significant difference between patients with varied age-adjusted CCI scores on the days of ICU stay.

Conclusion
The age-adjusted CCI is a valid indicator to predict death in ICU patients with cardiac arrest, which can offer enlightenment for both theory literatures and clinical practice.
Prognostic significance of serum CA125 in the overall management for patients with gastrointestinal stromal tumors
Authors: Sui Chao , Lin Chen , Tao Tingting , Guan Wenxian , Zhang Haoran , Tao Liang , Wang Meng , Wang Feng 
Published: January 2023

AbstractBackgroundCarbohydrate antigen 125 (CA125) is elevated as a tumor marker in many carcinomas, but its association with gastrointestinal stromal tumor (GIST) has received less attention. This study intends to evaluate whether CA125 level can predict tumor progression and overall survival (OS) of GIST patients.MethodsWe retrospectively analyzed the clinical data and follow-up records of GIST patients who underwent surgical resection in Nanjing Drum Tower Hospital from August 2010 to December 2020. All patients were classified according to serum CA125 level. The relationship between CA125 and clinical outcomes was then examined.ResultsA total of 406 GIST patients were enrolled in this study, among which 46 patients had preoperative elevated serum CA125 level and 13 patients with high CA125 level both preoperative and postoperative were observed. Preoperative CA125 concentration was significantly related to rupture status, resection style, tumor site, tumor size, mitotic index, NIH risk grade and c-kit exons. According to Kaplan–Meier curve analysis, high expression of postoperative CA125 was significantly correlated with worse progression-free survival (PFS) and OS among patients with preoperative elevated CA125 level. Ultimately, Cox proportional regression model analysis revealed that increase of preoperative and concurrent postoperative CA125 concentration was an independent predictive factor for PFS.ConclusionsThe concurrent abnormality of serum CA125 before and after operation was an independent risk factor for GIST progression, suggesting its significance as a serum biomarker in the overall management of GIST patients.