bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of the effectiveness of narrow-spectrum versus broad-spectrum antibiotics for the treatment of childhood pneumonia
Authors: Demeke Chilot Abiyu , Adinew Getnet Mequanent , Abebe Tamrat Befekadu , Gelaye Abebech Tewabe , Gemeda Sisay G/Hana , Yimenu Dawit Kumilachew 
Published: September 2021

Objectives: The main objective of this study was to compare the effectiveness of empiric treatment with narrow-spectrum therapy versus broad-spectrum therapy for children hospitalized with community-acquired pneumonia (CAP) at the University of Gondar Referral Hospital, Gondar, Ethiopia. Methods: Institutional-based retrospective chart review was conducted at the University of Gondar Referral Hospital (GURH) pediatrics ward from 1 February 2016 to 30 April 2016. The collected data were entered and analyzed using Statistical Package for Social Sciences (SPSS) version 20. Descriptive statistics were done to present the basic features and summary of the data set. In addition, binary logistics and multivariable logistic regression analysis were conducted to test for an association between the dependent and independent variables. A P value of <0.05 was taken to declare statistical significance at a 95% confidence interval. Result: A total of 147 patients with CAP were included in the study. Seven different treatment regimens were employed for the 147 children hospitalized. About 63 (42.9%) of the study participants received a narrow-spectrum antibiotic and 84 (57.1%) received a broad-spectrum antibiotic. There was no significant difference between the broad and narrow spectrum treatment groups in main treatment outcomes. The median length of stay (LOS) for the study population was 3 days. The median LOS was shorter among those receiving narrow-spectrum therapy compared with those receiving broad-spectrum therapy. Treatment dose and duration of therapy were significantly associated with treatment outcome (P < 0.0001 and P = 0.003), respectively. Conclusion: The effectiveness of narrow-spectrum therapy is similar to that of broad-spectrum therapy for children hospitalized with CAP. Treatment regimens for children with community-acquired pneumonia should be selected based on their safety profile and their tendency for antibiotic resistance.
Clinical Outcomes of Interposition Graft Versus Superior Capsular Reconstruction in Patients With Irreparable Rotator Cuff Tears: A Systematic Review and Meta-analysis
Authors: Baek Samuel , Shin Myung Ho , Kim Tae Min , Im Je Min , Oh Kyung-Soo , Chung Seok Won 
Published: September 2021

Background: Interposition grafting (IG), also called bridging grafting, and superior capsular reconstruction (SCR) are the most commonly used joint-preserving surgical methods for irreparable rotator cuff tears (RCTs). Purpose: To compare the effectiveness of IG versus SCR to treat patients with irreparable RCTs. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search was performed in MEDLINE, Embase, and Scopus. Included in this review were clinical studies evaluating the effect of IG or SCR in patients with irreparable RCTs with a minimum follow-up of 1 year. Various clinical results from the studies were extracted and compared between IG and SCR, and among them, the results of the American Shoulder and Elbow Surgeons score, graft retear rate, and complication rate were included in the meta-analysis. Results: Of 1638 identified articles, 17 (10 studies of IG involving 321 patients and 7 studies of SCR involving 357 patients) were selected. Both surgical methods showed significantly improved clinical outcomes in all but 1 study; however, the IG group had lower pain visual analog scale score, higher Constant score, and bigger active forward flexion and internal rotation compared with the SCR group (all P < .001). The meta-analysis showed no difference in the American Shoulder and Elbow Surgeons score between groups ( P = .44), but showed a significantly lower complication rate in the IG group compared with the SCR group (1.12% vs 8.37%, respectively; P < .001). The graft retear rate was not significantly different between groups (IG = 10.64% vs SCR = 12.67%; P = .79). The meta-analysis of graft type indicated no difference between groups in retear rate (autograft: 95% CI, 0.045-0.601; I2 = 93.28 [IG], 91.27 [SCR]; P = .22; allograft: 95% CI, 0.041-0.216; I2 = 80.39 [IG], 69.12 [SCR]; P = .64) or complication rate (autograft: 95% CI, 0.009-0.150; I2 = 0 [IG], 65.89 [SCR]; P = .25; allograft: 95% CI, 0.012-0.081; I2 = 0 [IG], 30.62 [SCR]; P = .09). Conclusion: Both IG and SCR techniques resulted in improvement in patients with irreparable RCTs. Meta-analysis showed a lower complication rate in the IG group; however, the lack of randomized studies limited our conclusions.
Renal cell carcinoma with malignant pleural effusion: Case report and systematic review of literature
Authors: Goyal Shikha , Vias Poorva , Periasamy Kannan , Madan Renu 
Published: September 2021

Introduction: Renal cell carcinoma metastasizes commonly to visceral organs such as adrenals, liver, lungs, or to bones. Metastases to body cavities such as pleura, pericardium and peritoneum are rare, and almost never in isolation. Case discussion: We discuss here a patient who was diagnosed with renal cell carcinoma following an episode of hematuria and underwent radical nephrectomy for the same. Within a month of surgery, he was evaluated for sudden onset breathlessness and detected to have massive left-sided pleural effusion, which returned malignant on pleural biopsy. The patient was treated with oral multikinase inhibitor following symptomatic therapy, with a favorable response. The imaging findings and relevant literature exploring the incidence of such presentations are discussed. Conclusion: Malignant effusions usually portend a poor prognosis but owing to the rarity of this condition and availability of newer therapies, long-term durable control may be expected.
Socioeconomic and Demographic Factors Contributing to COVID-19–Related Delays and Reductions in Primary Retinal Detachment Repair in a US Hot Spot
Authors: Port Alexander D. , Gong Dan , Shaikh Noreen , Loporchio Dean , Blaha Gregory R. , Eliott Dean , Miller John B. , Ness Steven 
Published: September 2021

Purpose: This work evaluates demographic and socioeconomic predictors of delayed care for rhegmatogenous retinal detachments (RRDs) during the spring 2020 COVID-19 shutdown in a US hot spot. Methods: This multicenter, retrospective, case-control study took place in 3 academic vitreoretinal practices in metropolitan Boston. Consecutive patients treated for RRD during the COVID-19 state of emergency were compared with patients treated during the same period in 2018 and 2019. The primary outcome was macula status for RRD. Secondary outcomes included visual acuity, symptom duration, proportion with proliferative vitreoretinopathy, time to procedure, method of repair, and patient demographics. Results: The total number of acute RRD decreased by 13.7% from 2018 to 2020 and 17.2% from 2019 to 2020. Symptom duration was significantly longer in 2020 than 2018 and 2019 (median, 7 vs 4 days) with a higher proportion of macula-off detachments (80 of 125 [64%] in 2020 vs 75 of 145 [51.7%] in 2018 and 78 of 151 [51.6%] in 2019). The 2020 cohort included significantly fewer patients in the racial and/or ethnic minority group than in 2019 ( P = .02), and use of low-income, government-sponsored health insurance was a predictor of macula-off status during the pandemic ( P = .04). Conclusions: RRDs during the spring 2020 COVID-19 lockdown were more likely to be macula-off at presentation. Because sociodemographic factors including race, ethnicity, and income level were associated with deferral of care, ophthalmologists should consider measures targeting vulnerable populations to avoid preventable vision loss as the pandemic continues or in future health care emergencies.
R4 RGS proteins suppress engraftment of human hematopoietic stem/progenitor cells by modulating SDF-1/CXCR4 signaling
Authors: Chan Kathy Yuen Yee , Zhang Chi , Wong Yorky Tsin Sik , Zhang Xiao-Bing , Wang Chi Chiu , Ng Wing Hei , Fok Siu Ping , Tang Patrick Ming Kuen , Kang Wei , Feng Bo , Poon Ellen Ngar Yun , Lee King Yiu , Lee Cheuk Kwong , Chen Chun , Leung Tak Yeung , Ng Margaret Heung Ling , To Ka Fai , Wang Han , Lam Hugh Simon , Ng Pak Cheung , Yuen Patrick Man Pan , Li Karen , Leung Alex Wing Kwan , Li Chi Kong , Leung Kam Tong 
Published: September 2021

Abstract
Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM) microenvironment are tightly regulated by the chemokine stromal cell–derived factor-1 (SDF-1) and its G-protein–coupled receptor C-X-C motif chemokine receptor 4 (CXCR4), which on engagement with G-protein subunits, trigger downstream migratory signals. Regulators of G-protein signaling (RGS) are GTPase-accelerating protein of the Gα subunit and R4 subfamily members have been implicated in SDF-1–directed trafficking of mature hematopoietic cells, yet their expression and influence on HSPCs remain mostly unknown. Here, we demonstrated that human CD34+ cells expressed multiple R4 RGS genes, of which RGS1, RGS2, RGS13, and RGS16 were significantly upregulated by SDF-1 in a CXCR4-dependent fashion. Forced overexpression of RGS1, RGS13, or RGS16 in CD34+ cells not only inhibited SDF-1–directed migration, calcium mobilization, and phosphorylation of AKT, ERK, and STAT3 in vitro, but also markedly reduced BM engraftment in transplanted NOD/SCID mice. Genome-wide microarray analysis of RGS-overexpressing CD34+ cells detected downregulation of multiple effectors with established roles in stem cell trafficking/maintenance. Convincingly, gain-of-function of selected effectors or ex vivo priming with their ligands significantly enhanced HSPC engraftment. We also constructed an evidence-based network illustrating the overlapping mechanisms of RGS1, RGS13, and RGS16 downstream of SDF-1/CXCR4 and Gαi. This model shows that these RGS members mediate compromised kinase signaling and negative regulation of stem cell functions, complement activation, proteolysis, and cell migration. Collectively, this study uncovers an essential inhibitory role of specific R4 RGS proteins in stem cell engraftment, which could potentially be exploited to develop improved clinical HSPC transplantation protocols.
Emergence of bedaquiline resistance in a high tuberculosis burden country
Authors: Chesov Elena , Chesov Dumitru , Maurer Florian P. , Andres Sönke , Utpatel Christian , Barilar Ivan , Donica Ana , Reimann Maja , Niemann Stefan , Lange Christoph , Crudu Valeriu , Heyckendorf Jan , Merker Matthias 
Published: September 2021

RationaleBedaquiline has been classified as a group A drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) by the World Health Organization; however, globally emerging resistance threatens the effectivity of novel MDR-TB treatment regimens.ObjectivesWe analysed pre-existing and emerging bedaquiline resistance in bedaquiline-based MDR-TB therapies, and risk factors associated with treatment failure and death.MethodsIn a cross-sectional cohort study, we employed patient data, whole-genome sequencing (WGS) and phenotyping ofMycobacterium tuberculosiscomplex (MTBC) isolates. We could retrieve baseline isolates from 30.5% (62 out of 203) of all MDR-TB patients who received bedaquiline between 2016 and 2018 in the Republic of Moldova. This includes 26 patients for whom we could also retrieve a follow-up isolate.Measurements and main resultsAt baseline, all MTBC isolates were susceptible to bedaquiline. Among 26 patients with available baseline and follow-up isolates, four (15.3%) patients harboured strains which acquired bedaquiline resistance under therapy, while one (3.8%) patient was re-infected with a second bedaquiline-resistant strain. Treatment failure and death were associated with cavitary disease (p=0.011), and any additional drug prescribed in the bedaquiline-containing regimen with WGS-predicted resistance at baseline (OR 1.92 per unit increase, 95% CI 1.15–3.21; p=0.012).ConclusionsMDR-TB treatments based on bedaquiline require a functional background regimen to achieve high cure rates and to prevent the evolution of bedaquiline resistance. Novel MDR-TB therapies with bedaquiline require timely and comprehensive drug resistance monitoring.
The novel bronchodilator navafenterol: a phase 2a, multicentre, randomised, double-blind, placebo-controlled crossover trial in COPD
Authors: Singh Dave , Beier Jutta , Astbury Carol , Belvisi Maria G. , Da Silva Carla A. , Jauhiainen Alexandra , Jimenez Eulalia , Lei Alejhandra , Necander Sofia , Smith Jaclyn A. , Wählby Hamrén Ulrika , Xin Wenjing , Psallidas Ioannis 
Published: September 2021

BackgroundNavafenterol (AZD8871) belongs to a new class of bronchodilator, the single-molecule muscarinic antagonist and β-agonist, developed for the treatment of COPD. This study aimed to evaluate the efficacy, pharmacokinetics and safety of navafenterolversusplacebo and an active comparator treatment for moderate-to-severe COPD.MethodsThis phase 2a, randomised, multicentre (Germany and UK), double-blind, double-dummy, three-way complete crossover study (ClinicalTrials.gov identifier:NCT03645434) compared 2 weeks’ treatment of once-daily navafenterol 600 µgviainhalation with placebo and a fixed-dose combination bronchodilator (umeclidinium/vilanterol (UMEC/VI); 62.5 µg/25 µg) in participants with moderate-to-severe COPD. The primary outcome was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 15. Secondary end-points included change from baseline in peak FEV1; change from baseline in Breathlessness, Cough and Sputum Scale (BCSS); change from baseline in COPD Assessment Tool (CAT); adverse events; and pharmacokinetics.Results73 participants were randomised. After 14 days, trough FEV1was significantly improved with navafenterol compared with placebo (least-squares (LS) mean difference 0.202 L; p<0.0001). There was no significant difference in FEV1between navafenterol and UMEC/VI (LS mean difference −0.046 L; p=0.075). COPD symptoms (CAT and BCSS) showed significantly greater improvements with both active treatmentsversusplacebo (all p<0.005). Novel objective monitoring (VitaloJAK) showed that cough was reduced with both active treatments compared with placebo. Safety profiles were similar across the treatment groups and no serious adverse events were reported in the navafenterol treatment period.ConclusionOnce-daily navafenterol was well tolerated, improved lung function and reduced COPD-related symptoms, similar to an established once-daily fixed-dose combination bronchodilator.
Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children
Authors: Mensink-Bout Sara M. , van Meel Evelien R. , de Jongste Johan C. , Annesi-Maesano Isabella , Aubert Adrien M. , Bernard Jonathan Y. , Chen Ling-Wei , Cooper Cyrus , Crozier Sarah R. , Hanke Wojciech , Harvey Nicholas C. , Hébert James R. , Heude Barbara , Jerzynska Joanna , Kelleher Cecily C. , Mehegan John , McAuliffe Fionnuala M. , Phillips Catherine M. , Polanska Kinga , Relton Caroline L. , Shivappa Nitin , Suderman Matthew , Jaddoe Vincent W.V. , Duijts Liesbeth 
Published: September 2021

RationaleSevere fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health.MethodsWe performed an individual participant meta-analysis among 18 326 mother–child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry.ResultsAfter adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference −0.05, 95% CI −0.08– −0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <−1.64) (OR 1.20, 95% CI 1.06–1.36 and z-score difference 1.40, 95% CI 1.06–1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively.ConclusionThe main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.
Lower airway clinical outcome measures for use in primary ciliary dyskinesia research: a scoping review
Authors: Gahleitner Florian , Thompson James , Jackson Claire L. , Hueppe Jana F. , Behan Laura , Dehlink Eleonora , Goutaki Myrofora , Halbeisen Florian , Queiroz Ana Paula L. , Thouvenin Guillaume , Kuehni Claudia E. , Latzin Philipp , Lucas Jane S. , Rubbo Bruna 
Published: September 2021

ObjectivesDisease-specific, well-defined and validated clinical outcome measures are essential in designing research studies. Poorly defined outcome measures hamper pooling of data and comparisons between studies. We aimed to identify and describe pulmonary outcome measures that could be used for follow-up of patients with primary ciliary dyskinesia (PCD).MethodsWe conducted a scoping review by systematically searching MEDLINE, Embase and the Cochrane Database of Systematic Reviews online databases for studies published from 1996 to 2020 that included ≥10 PCD adult and/or paediatric patients.ResultsWe included 102 studies (7289 patients). 83 studies reported on spirometry, 11 on body plethysmography, 15 on multiple-breath washout, 36 on high-resolution computed tomography (HRCT), 57 on microbiology and 17 on health-related quality of life. Measurement and reporting of outcomes varied considerably between studies (e.g.different scoring systems for chest HRCT scans). Additionally, definitions of outcome measures varied (e.g.definition of chronic colonisation by respiratory pathogen), impeding direct comparisons of results.ConclusionsThis review highlights the need for standardisation of measurements and reporting of outcome measures to enable comparisons between studies. Defining a core set of clinical outcome measures is necessary to ensure reproducibility of results and for use in future trials and prospective cohorts.
4-week daily airway clearance using oscillating positive-end expiratory pressureversusautogenic drainage in bronchiectasis patients: a randomised controlled trial
Authors: Livnat Galit , Yaari Naama , Stein Nili , Bentur Lea , Hanna Moneera , Harel Maya , Adir Yochai , Shteinberg Michal 
Published: September 2021

BackgroundAirway clearance is a fundamental component of bronchiectasis care. Lung clearance index (LCI) is a measurement of ventilation inhomogeneity. Its responsiveness to long-term airway clearance is unknown. We aimed to compare two methods of daily airway clearance over 4 weeks: autogenic drainage (AD) and oscillating positive airway pressure (oPEP), and to determine effects of airway clearance on LCI and clinical outcomes.MethodsAdults with bronchiectasis naive to airway clearance were randomised to daily airway clearance with either AD or oPEP. Difference in LCI as primary outcome, spirometry, sputum volume and purulence, and quality of life were at randomisation and after 4 weeks of airway clearance.Results51 patients (32 women and 19 men, mean age 66.2±12.8 years) were randomised and 49 completed the study (25 AD and 24 oPEP). The LCI and forced expiratory volume in 1 s did not change between visits between groups (difference between groups 0.02), nor between visits in either group. Sputum quantity decreased in 12 out of 24 (50%) of the oPEP group, and in six out of 25 (24%) of the AD group (p=0.044). The “treatment burden” worsened or was unchanged in 70% of participants randomised to AD and 55% randomised to oPEP (p=0.038).ConclusionSputum quantity decreased in more participants randomised to oPEP group after 1 month of daily airway clearance, with a better treatment burden. The effects of 4 weeks of airway clearance on LCI were not significant in either treatment group.
METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho
Authors: Li Manna , Deng Le , Xu Gaosi 
Published: September 2021

Abstract
Background
N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. However, its functions in diabetic nephropathy (DN) have not been determined. Here, we investigated the role of METTL14, a key component of the m6A methyltransferase complex, in DN.

Methods
The expression of METTL14 was detected in DN patients and human renal glomerular endothelial cells (HRGECs). In vitro and in vivo experiments were performed to explore the functions of METTL14 on high glocse-induced HRGECs and renal injury of DN mice. We also investigated whether METTL14 works by regulating α-klotho expression through m6A modification.

Results
METTL14 were highly expressed in kidneys of DN patients and high glocse-induced HRGECs both at the mRNA and protein level. Overexpression of METTL14 increased ROS, TNF-α and IL-6 levels and apoptosis in HRGECs. Conversely, METTL14 silence decreased the levels of ROS, TNF-α and IL-6 and cell apoptosis. We confirmed that METTL14 down-regulated α-klotho expression in an m6A-dependent manner. In addition, we also found that METTL14 aggravated renal injury and inflammation of db/db mice, which could partially rescued by α-klotho.

Conclusion
Our data revealed that METTL14 plays a vital role in high glucose-induced glomerular endothelial cells and diabetic nephropathy through m6A modification of α-klotho.