bluuebunny/crossref_metadata_2025 huggingface dataset:
Modalities of Post-Rhinoplasty Edema and Ecchymosis Measurement: A Systematic Review
Authors: Levin Marc , Ziai Hedyeh , Roskies Michael
Published: April 2021

Background:

Post-rhinoplasty edema and ecchymosis can influence patient satisfaction with surgery as well as result in poor quality of life. Methods to quantify such edema and ecchymosis have been described in the literature. Despite this, there is currently no collective understanding of which methods are the most effective. Hence, this systematic review aims to describe and analyze the literature on post-rhinoplasty edema and ecchymosis measurement techniques.

Methods:

Standard bibliographic databases (OVID Medline, EMBASE, and PubMed) were searched from their inception to December 2019 for the terms: “rhinoplasty”, “postoperative”, “edema”, and “ecchymosis”. Descriptive analysis was completed.

Results:

The search revealed 1116 articles of which 33 met inclusion criteria and were included for qualitative synthesis. A total of 1801 patients from all studies were included. Of the 33 included studies, there were 57 unique ecchymosis/edema measurements. The majority of studies measured edema/ecchymosis on post-operative day 1, 2, 3 and 7. Ninety-three percent of measurements described were taken subjectively from a human rater. Other techniques described included magnetic resonance imaging, ultrasound, 3-dimensional imaging, and digital analysis. Less than half of the subjective ecchymosis/edema gradings were completed by a blinded rater.

Conclusion:

There are a wide variety of post-rhinoplasty edema and ecchymosis techniques being used by rhinoplasty surgeons. The majority of post-rhinoplasty edema and ecchymosis measurements are completed by unblinded subjective raters. It is important that facial plastic surgeons select an accurate measurement tool so they may be able to initiate precise patient-specific management of edema and ecchymosis.
Repair versus biceps tenodesis for the slap tears: A systematic review
Authors: Civan Osman , Bilsel Kerem , Kapicioglu Mehmet , Ozenci Alpay M
Published: April 2021

Purpose:

The ideal treatment algorithm is still controversial for Superior Labral Anterior-Posterior (SLAP) tears. In this systematic review, we aimed to clarify and ascertain which treatment modality is effective and more usable in which conditions.

Methods:

In this systematic review, we used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines established for systematic reviews and meta-analysis. “SLAP or Superior Labral Anterior-Posterior” and “biceps tenodesis” search terms were used in The Cochrane Library database and Pubmed from their inception to the 30th of September 2020. A total of 2326 titles were screened and 2069 articles were removed because of their ineligibility. Full texts of 14 studies were screened and finally, six were suitable for the present systematic review. Demographic details and study characteristics, patient satisfaction, functional outcomes, return to preinjury sports level, reoperation, stiffness, sling time and rehabilitation protocols were reviewed and compared between SLAP repair and biceps tenodesis groups.

Results:

A total of 2326 titles were screened and six studies were detected eligible. Results of 287 patients (SLAP repair: 160, Biceps Tenodesis: 127) were reviewed in included six studies. Biceps tenodesis was showed as more satisfied technique in four of the studies but the statistical comparing results of two groups were not significantly different in each study. Different functional scoring systems used in the studies were not statistically significantly different between the groups. The percentage of return to sport and preinjury level is higher in biceps tenodesis in the five studies. The total reoperation rate for SLAP repair was 19/160 (12%) and biceps tenodesis was 7/127 (6%).

Conclusion:

The biceps tenodesis has a higher return to preinjury sports level, higher patient satisfaction and lower reoperation rates but functional scores are similar between SLAP repair groups in patients with SLAP tear.
Land Tenure, Land Property Rights and Adoption of Bio-fortified Cassava in Nigeria: Policy Implications
Authors: Adetomiwa Kolapo , Iseoluwa Abimbola Esther , Babatunde Omilaju Samuel
Published: April 2021

This study investigated land tenure, land right and rental system, as it relates to adoption of bio-fortified cassava in Nigeria. The study was conducted in three states in Nigeria where bio-fortified cassava technology was first released in Nigeria including Oyo, Benue and Akwa Ibom. Multistage sampling techniques were used to select 360 bio-fortified cassava farmers. Descriptive statistics, t-test and Cragg’s double hurdle model were used to analyse the data collected. The land tenure system practised in the bio-fortified cassava-producing areas in Nigeria is governed by inheritance (23%), purchasing (19.7), gifting (31.7) and temporary arrangements through rentals (25.6%). The tenant bio-fortified cassava farmers pay about ₦31,000 per acre per year in land for cash agreement or 4%–7% of the actual yield of the bio-fortified cassava in land for cassava outputs agreements. However, this agreement between the landlords and tenant bio-fortified cassava farmers is verbal where both parties try as much as possible to honour the agreements. Variables such as access to credit, landownership status, access to bio-fortified cassava stems and extension contacts influenced the decision to adopt bio-fortified cassava technology, while age, perception and training influenced the intensity of adoption of bio-fortified cassava technology. The result of the t-test analysis showed that there was a significant difference in the farm sizes (34739.467 at 1%) and yields (0.593 at 1%) of the landlords and tenant bio-fortified cassava farmers. The findings of the study indicated that tenant bio-fortified cassava farmers were being faced with the problem of insecure land access, thus the need to implement policies that will increase access to land resources among the tenant farmers in Nigeria.
Impact of COVID-19 Lockdown on Pulmonary and Nutritional Status in Children and Young Adults With Cystic Fibrosis, in Greece
Authors: Loukou Ioanna , Moustaki Maria , Petrocheilou Argyri , Zarkada Ioanna , Douros Konstantinos
Published: April 2021

During the first wave of the coronavirus pandemic in 2020, Greece adopted strict lockdown measures. We aimed to investigate the effects of lockdown and the resultant changes in the standard of care, on the lung function and somatic growth of cystic fibrosis (CF) patients. We analyzed data on body mass index and lung function of 103 CF patients 5.0- to 23.0-years-old before and after the lockdown period. Body mass index did not change significantly, but there was a significant improvement in lung function after the end of the lockdown period.
Party Polarization and Trust in Science: What about Democrats?
Authors: Lee John J.
Published: April 2021

Research has documented the decline of trust in science among Republicans, ideological conservatives, and fundamentalist religious groups. However, less is known about the nature of party polarization in these trends: did polarization only increase because of changes among Republicans? In this study, the author tests a two-sided polarization thesis using data from the General Social Survey (1974–2018). The findings show that a significant share of the growth in party polarization is due to an increase of trust in science among Democrats. In fact, by the 2010s, Democrats became significantly more likely than either Republicans or independents to have high confidence in science. Moreover, the results also show that the aggregate party-level changes are driven largely by trends among conservative Republicans, moderate Democrats, and liberal Democrats. Together, these findings have implications for our understanding of the nature and potential causes of partisan polarization in beliefs about the cultural authority of science.
A participatory local governance approach to social innovation: A case study of Seongbuk-gu, South Korea
Authors: Kim Sangmin
Published: April 2021

As the concept of social innovation gains increasing credence in the public consciousness, a number of questions have become increasingly prominent in the relevant discourse: what does social innovation mean at the local level? How can social innovation be promoted? In particular, what kinds of social and institutional arrangements are needed to facilitate socially innovative activities and practices in neighborhoods and communities? To address these questions, this paper first outlines the related theories and literature as an overview of the notion of social innovation. Next, to provide an example of a promising approach to social innovation at the local level, the paper develops a theoretical discussion on the interface between local social innovation and participatory local governance arrangements, and proposes a process model of local social innovation as an analytical framework for a case study of a district-level initiative in Seongbuk-gu in Seoul, South Korea. By examining the governance structure and socially innovative strategies utilized in this locality, the case study demonstrates how the local participatory governance system can furnish an enabling environment for socially innovative ideas and strategies. Lastly, along with a look at some of the unique aspects of the case, the paper discusses contributions of this study to the theory and practice of social innovation, along with implications for other cases that may consider the governance approach to social innovation.
Preliminary Validation of the Severity of Nail Psoriasis Score (SNAPS) for the Assessment of Nail Psoriasis in Patients With Psoriatic Arthritis
Authors: Antony Anna , Saeed Sadaf , Hart Darren , Nair Preeti , Cavill Charlotte , Korendowych Eleanor , McHugh Neil , Lovell Christopher , Tillett William
Published: April 2021

Background:

Psoriatic nail dystrophy is infrequently assessed in routine care and observational cohorts due to the lack of a feasible validated outcome measure.

Objective:

To assess the measurement properties of the “Severity of NAil Psoriasis Score” (SNAPS) in PsA.

Methods:

Nail photography was performed on prospectively recruited patients at baseline and 6 months. The modified Nail Psoriasis Severity Index (mNAPSI) and Physician Nail Visual Acuity Scale (PhNVAS) were comparator instruments for construct validity. Reliability and feasibility were assessed using intra-class correlations (ICCs) and timed scoring. Responsiveness was assessed by correlating the changes in SNAPS, mNAPSI and PhNVAS. Retrospective data from the Bath PsA database was further utilized to assess responsiveness.

Results:

21 patients participated in the prospective validation at baseline. Inter- and intra-rater reliability of SNAPS were 0.94 and 0.93-0.96 (p ≤ 0.005). Mean times required to score SNAPS and mNAPSI were 59 and 136 seconds. There were strong correlations between SNAPS and mNAPSI (r = 0.95, p < 0.001) and PhNVAS (r = 0.77, p < 0.001) at baseline. There was a significant reduction in the mNAPSI and SNAPS (p < 0.005) at 6 months and a strong correlation between the change in SNAPS and mNAPSI (rho = 0.838, p < 0.001). Historical data from 57 patients commenced on Etanercept were evaluated. Mean SNAPS reduced from 3.6 to 2.0 at 3 months and 1.2 at 6 months (p < 0.05). Change in SNAPS correlated with changes in Psoriasis Area Severity Index and Dermatology Quality of Life at 3 and 6 months (r≥0.510; p ≤ 0.003).

Conclusion:

SNAPS is a feasible, reliable and responsive outcome instrument for psoriatic nail dystrophy.
Nanosecond and sub-nanosecond laser-assisted microscribing of Cu thin films in a salt solution
Authors: Shiby Sooraj , Vasa Nilesh J , Shigeki Matsuo
Published: April 2021

Pulsed laser-based material removal is a preferred technique for microscribing of copper (Cu) film coated on polymers, as the pulse width limits the heat diffusion. However, experimental studies have shown that microscribing of Cu in air results in recast/redeposit formation and oxidation. Although the water medium can reduce these effects to a certain extent, the material removal rate is lesser for Cu. This article reports the influence of laser pulse duration on a hybrid method to enhance the pulsed laser-assisted microscribing of a copper thin film in the presence of an environmentally friendly sodium chloride salt solution (NaCl). The focused laser beam irradiation of Cu film results in ablation with a temperature of the zone well above the boiling point of Cu, which in turn, can assist in accelerating the chemical reaction. In this hybrid scribing technique, along with laser-based material removal, laser-activated chemical etching also helps in removing the material selectively. A sub-nanosecond laser with a pulse width of 500 ps (picosecond [ps] laser) and a nanosecond laser with a pulse width of 6 ns (nanosecond [ns] laser), with a wavelength of 532 nm, are used to understand the influence of laser pulse duration on this hybrid material removal mechanism. Hybrid microscribing with the ps- and ns lasers in salt solution resulted in an increase in the channel depth by ≈5 µm and ≈9 µm, respectively, compared to the channel depth obtained in deionized water. The theoretical model shows that during the ns laser ablation, the cooling rate is slower, resulting in a high temperature in the ablation zone for a longer duration and improved material removal.
Implications of Recent Revelations from Basic and Clinical Studies of Barrett’s Esophagus for Screening and Surveillance Strategies
Authors: Spechler Stuart Jon , Souza Rhonda F.
Published: April 2021

During the past several decades, while the incidence of esophageal adenocarcinoma (EAC) has risen dramatically, our primary EAC-prevention strategies have been endoscopic screening of individuals with GERD symptoms for Barrett’s esophagus (BE), and endoscopic surveillance for those found to have BE. Unfortunately, current screening practices have failed to identify most patients who develop EAC, and the efficacy of surveillance remains highly questionable. We review potential reasons for failure of these practices including recent evidence that most EACs develop through a rapid genomic doubling pathway, and recent data suggesting that many EACs develop from segments of esophageal intestinal metaplasia too short to be recognized as BE. We highlight need for a biomarker to identify BE patients at high risk for neoplasia (who would benefit from early therapeutic intervention), and BE patients at low risk (who would not benefit from surveillance). Promising recent efforts to identify such a biomarker are reviewed herein.
The Utility of Biomarkers for Risk Stratification in Barrett’s Esophagus
Authors: Konda Vani J.A. , Ellison Ashton
Published: April 2021

Challenges remain to determine which patients with Barrett’s esophagus with no dysplasia or low-grade dysplasia would benefit from therapy or tailored surveillance intervals. Biomarkers have the potential to improve risk stratification in Barrett’s esophagus through predictive capability and ease of use. We highlight biomarkers investigated in risk stratification in Barrett’s esophagus including p53 aberrancy, chromosomal derangements, immunofluorescence-based panels, and DNA methylation panels. We explore non-endoscopic approaches that may be implemented in the office-based setting and discuss the utility of sample collection in patients with Barrett’s esophagus and in the broader population.
Single-center experience with venetoclax combinations in patients with newly diagnosed and relapsed AML evolving from MPNs
Authors: Masarova Lucia , DiNardo Courtney D. , Bose Prithviraj , Pemmaraju Naveen , Daver Naval G. , Kadia Tapan M. , Chifotides Helen T. , Zhou Lingsha , Borthakur Gautam , Estrov Zeev , Konopleva Marina , Verstovsek Srdan
Published: April 2021

In patients with acute myeloid leukemia evolving from myeloproliferative neoplasms (post–MPN-AML), the clinical activity of the B-cell lymphoma 2 inhibitor venetoclax remains to be determined. We review our experience with venetoclax-based regimens in 14 newly diagnosed (frontline [FL]) and 17 relapsed/refractory (R/R) post–MPN-AML patients. Venetoclax was used in combination with hypomethylating agents in 58% of cases and in 19% with intensive chemotherapy (treatment including cytarabine ≥1 g/m2 or CPX-351); the remaining patients received cladribine and low-dose cytarabine or isocitrate dehydrogenase 1/2 inhibitors. The median dose of venetoclax during the initial cycle was 100 mg in all patients (range, 50-800 mg) and 200 mg (range, 100-800 mg) for FL patients. The venetoclax dose was adjusted when used concomitantly with azole antifungal agents. In FL patients, complete remission with and without count recovery in 6 patients (median duration of 6.4 months) and partial remission in 1 patient was noted, with a median overall survival of 7 months. In R/R patients, no formal responses were seen, with a median overall survival of 3 months. Hematologic toxicities and adverse events were frequent; 83% of patients developed grade 3 or higher infection during the initial cycle. Severe hemorrhagic complications were observed in 14 patients, including 6 cases of intracranial and subdural hemorrhage. Overall 4-week and 8-week mortality were 10% and 32%, respectively. Given the substantial treatment-associated hematologic toxicity and mortality, and modest short-lived responses only in newly diagnosed patients with venetoclax-based regimens, additional treatment options are urgently needed for these patients.
Impact of splicing mutations in acute myeloid leukemia treated with hypomethylating agents combined with venetoclax
Authors: Lachowiez Curtis A. , Loghavi Sanam , Furudate Ken , Montalban-Bravo Guillermo , Maiti Abhishek , Kadia Tapan , Daver Naval , Borthakur Gautam , Pemmaraju Naveen , Sasaki Koji , Alvarado Yesid , Yilmaz Musa , Short Nicholas J. , Chien Kelly , Ohanian Maro , Pierce Sherry , Patel Keyur P. , Jabbour Elias , Ravandi Farhad , Kantarjian Hagop M. , Garcia-Manero Guillermo , Takahashi Koichi , Konopleva Marina Y. , DiNardo Courtney D.
Published: April 2021

Spliceosome mutations (SRSF2, SF3B1, U2AF1, ZRSR2), are encountered in ∼50% of secondary acute myeloid leukemia cases (sAML) and define a molecular subgroup with outcomes similar to sAML in de novo AML patients treated with intensive chemotherapy. Outcomes in patients with spliceosome mutations treated with hypomethylating agents in combination with venetoclax (HMA+VEN) remains unknown. The primary objective was to compare outcomes in patients with spliceosome mutations vs wild-type patients treated with HMA+VEN. Secondary objectives included analysis of the mutational landscape of the spliceosome cohort and assessing the impact of co-occurring mutations. We performed a retrospective cohort analysis of patients treated with HMA+VEN–based regimens at The University of Texas MD Anderson Cancer Center. A total of 119 patients (spliceosome mutated n = 39 [SRSF2, n = 24; SF3B1, n = 8; U2AF1, n = 7]; wild-type, n = 80) were included. Similar responses were observed between spliceosome and wild-type cohorts for composite complete response (CRc; 79% vs 75%, P = .65), and measurable residual disease–negative CRc (48% vs 60%, P = .34). Median overall survival for spliceosome vs wild-type patients was 35 vs 14 months (P = .58), and was not reached; 35 months and 8 months for patients with SRSF2, SF3B1, and U2AF1 mutations, respectively. IDH2 mutations were enriched in patients with SRSF2 mutations and associated with favorable outcomes (1- and 2-year overall survival [OS] of 100% and 88%). RAS mutations were enriched in patients with U2AF1 mutations and associated with inferior outcomes (median OS, 8 months). Comparable outcomes were observed between patients with vs without spliceosome mutations treated with HMA+VEN regimens, with specific co-mutation pairs demonstrating favorable outcomes.
Psychometrics of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis
Authors: McLeese Rebecca H. , Spinou Arietta , Alfahl Zina , Tsagris Michail , Elborn J. Stuart , Chalmers James D. , De Soyza Anthony , Loebinger Michael R. , Birring Surinder S. , Fragkos Konstantinos C. , Wilson Robert , O'Neill Katherine , Bradley Judy M.
Published: April 2021

Introduction

Understanding the psychometric properties of health-related quality of life (HRQoL) questionnaires can help inform selection in clinical trials. Our objective was to assess the psychometric properties of HRQoL questionnaires in bronchiectasis using a systematic review and meta-analysis of the literature.

Methods

A literature search was conducted. HRQoL questionnaires were assessed for psychometric properties (reliability, validity, minimal clinically important difference (MCID) and floor/ceiling effects). Meta-analyses assessed the associations of HRQoL with clinical measures and responsiveness of HRQoL in clinical trials.

Results

166 studies and 12 HRQoL questionnaires were included. The Bronchiectasis Health Questionnaire (BHQ), Leicester Cough Questionnaire (LCQ), Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) had good internal consistency in all domains reported (Cronbach's α≥0.7) across all studies, and the Quality of Life-Bronchiectasis (QOL-B), St George's Respiratory Questionnaire (SGRQ), Chronic Respiratory Disease Questionnaire (CRDQ) and Seattle Obstructive Lung Disease Questionnaire (SOLQ) had good internal consistency in all domains in the majority of (but not all) studies. BHQ, SGRQ, LCQ and CAT had good test–retest reliability in all domains reported (intraclass correlation coefficient ≥0.7) across all studies, and QOL-B, CRDQ and SOLQ had good test–retest reliability in all domains in the majority of (but not all) studies. HRQoL questionnaires were able to discriminate between demographics, important markers of clinical status, disease severity, exacerbations and bacteriology. For HRQoL responsiveness, there was a difference between the treatment and placebo effect.

Conclusions

SGRQ was the most widely used HRQoL questionnaire in bronchiectasis studies and it had good psychometric properties; however, good psychometric data are emerging on the bronchiectasis-specific HRQoL questionnaires QOL-B and BHQ. Future studies should focus on the medium- to long-term test–retest reliability, responsiveness and MCID in these HRQoL questionnaires which show potential in bronchiectasis.
Recommendations for respiratory syncytial virus surveillance at the national level
Authors: Teirlinck Anne C. , Broberg Eeva K. , Stuwitz Berg Are , Campbell Harry , Reeves Rachel M. , Carnahan AnnaSara , Lina Bruno , Pakarna Gatis , Bøås Håkon , Nohynek Hanna , Emborg Hanne-Dorthe , Nair Harish , Reiche Janine , Oliva Jesus Angel , O’Gorman Joanne , Paget John , Szymanski Karol , Danis Kostas , Socan Maja , Gijon Manuel , Rapp Marie , Havlíčková Martina , Trebbien Ramona , Guiomar Raquel , Hirve Siddhivinayak S. , Buda Silke , van der Werf Sylvie , Meijer Adam , Fischer Thea K.
Published: April 2021

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.
Interstitial lung disease increases susceptibility to and severity of COVID-19
Authors: Lee Hyun , Choi Hayoung , Yang Bumhee , Lee Sun-Kyung , Park Tai Sun , Park Dong Won , Moon Ji-Yong , Kim Tae-Hyung , Sohn Jang Won , Yoon Ho Joo , Kim Sang-Heon
Published: April 2021

Background

There are limited data regarding the relationship between interstitial lung disease (ILD) and the natural course of COVID-19. In this study, we investigate whether patients with ILD are more susceptible to COVID-19 than those without ILD and evaluate the impact of ILD on disease severity in patients with COVID-19.

Methods

A nationwide cohort of patients with COVID-19 (n=8070) and a 1:15 age-, sex- and residential area-matched cohort (n=121 050) were constructed between 1 January 2020 and 30 May 2020 in Korea. We performed a nested case–control study to compare the proportions of patients with ILD between the COVID-19 cohort and the matched cohort. Using the COVID-19 cohort, we also evaluated the risk of severe COVID-19 in patients with ILDversusthose without ILD.

Results

The proportion of patients with ILD was significantly higher in the COVID-19 cohort than in the matched cohort (0.8%versus0.4%; p<0.001). The odds of having ILD was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR 2.02, 95% CI 1.54–2.61). Among patients in the COVID-19 cohort, patients with ILD were more likely to have severe COVID-19 than patients without ILD (47.8%versus12.6%), including mortality (13.4%versus2.8%) (all p<0.001). The risk of severe COVID-19 was significantly higher in patients with ILD than in those without ILD (adjusted OR 2.23, 95% CI 1.24–4.01).

Conclusion

The risks of COVID-19 and severe presentation were significantly higher in patients with ILD than in those without ILD.
Design and rationale of a randomised, double-blind trial of the efficacy and safety of pirfenidone in patients with fibrotic hypersensitivity pneumonitis
Authors: Fernández Pérez Evans R. , Crooks James L. , Swigris Jeffrey J. , Solomon Joshua J. , Mohning Michael P. , Huie Tristan J. , Koslow Matthew , Lynch David A. , Groshong Steve D. , Fier Kaitlin
Published: April 2021

Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease resulting from inhalational exposure to any of a large variety of antigens. A subgroup of patients with HP develops pulmonary fibrosis (fibrotic HP; FHP), a significant cause of morbidity and mortality. This study will evaluate the safety and efficacy of the antifibrotic pirfenidone in treating FHP.

This single-centre, randomised, double-blind, placebo-controlled trial is enrolling adults with FHP (ClinicalTrials.gov:NCT02958917). Study participants must have fibrotic abnormalities involving ≥5% of the lung parenchyma on high-resolution computed tomography scan, forced vital capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised in a 2:1 ratio to receive pirfenidone 2403 mg·day−1or placebo. The primary efficacy end-point is the mean change in FVC % predicted from baseline to week 52. A number of secondary end-points have been chosen to evaluate the safety and efficacy in different domains.
Acute and durable effect of inhaled hypertonic saline on mucociliary clearance in adult asthma
Authors: Bennett William D. , Burbank Allison , Almond Martha , Wu Jihong , Ceppe Agathe , Hernandez Michelle , Boucher Richard C. , Peden David B.
Published: April 2021

Background

Impaired mucus clearance and airway mucus plugging have been shown to occur in moderate–severe asthma, especially during acute exacerbations. In cystic fibrosis, where airway mucus is dehydrated, it has been shown that inhaled hypertonic saline (HS) produces both acute and sustained enhancement of mucociliary clearance (MCC). The current study was designed to assess the acute and sustained effect of inhaled 7% HS on MCC in adult asthma.

Methods

Well-controlled, moderate–severe female asthmatic patients (n=8) were screened with a single test dose of albuterol (four puffs by metered-dose inhaler) followed by HS (7% sodium chloride, 4 mL using PARI LC Star nebuliser). Spirometry was measured pre-treatment and 5 and 30 min post-treatment for safety. MCC was measured using γ-scintigraphy on three separate visits: at baseline, during inhalation and 4 h after a single dose of HS.

Results

MCC was acutely enhanced during HS treatment; mean±sdclearance over 60 min of dynamic imaging (Ave60Clr) was 8.9±7.9% (baseline)versus23.4±7.6% (acute HS) (p<0.005). However, this enhancement was not maintained over a 4-h period where post-HS treatment Ave60Clr was 9.3±8.2%. In this small cohort we found no decrements in lung function up to 30 min post-treatment (forced expiratory volume in 1 s 97.4±10.0% predicted pre-treatment and 98.9±10.7% predicted 30 min post-treatment).

Conclusion

While MCC was rapidly enhanced during 7% HS treatment there was no effect on MCC at 4 h post-treatment. While these findings may not support aerosolised HS use for maintenance therapy, they do suggest a benefit of treating acute exacerbations in patients with moderate–severe asthma.
Early risk prediction in idiopathicversusconnective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment
Authors: Hjalmarsson Clara , Kjellström Barbro , Jansson Kjell , Nisell Magnus , Kylhammar David , Kavianipour Mohammad , Rådegran Göran , Söderberg Stefan , Wikström Gerhard , Wuttge Dirk M. , Hesselstrand Roger
Published: April 2021

Despite systematic screening and improved treatment strategies, the prognosis remains worse in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) compared to patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH). We aimed to investigate differences in clinical characteristics, outcome and performance of the European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk stratification tool in these patient groups.

 This retrospective analysis included incident patients with CTD-PAH (n=197, of which 64 had interstitial lung disease, ILD) or IPAH (n=305) enrolled in the Swedish PAH Register (SPAHR) 2008–2019. Patients were classified as low, intermediate or high risk at baseline, according to the “SPAHR-equation”. One-year survival, stratified by type of PAH, was investigated by Cox proportional regression.

 At baseline, CTD-PAH patients had lower diffusing capacity for carbon monoxide and lower haemoglobin but, at the same time, lower N-terminal prohormone-brain natriuretic peptide, longer 6 min walk distance, better haemodynamics and more often a low-risk profile. No difference in age, World Health Organisation functional class (WHO-FC) or renal function between groups was found. One-year survival rates were 75, 82 and 83% in patients with CTD-PAH with ILD, CTD-PAH without ILD and IPAH, respectively. The 1-year mortality rates for low-, intermediate- and high-risk groups in the whole cohort were 0, 18 and 34% (p<0.001), respectively. Corresponding percentages for CTD-PAH with ILD, CTD-PAH without ILD and IPAH patients were: 0, 26, 67% (p=0.008); 0, 19, 39% (p=0.004); and 0, 16, 29% (p=0.001), respectively.

 The ESC/ERS risk assessment tool accurately identified low-risk patients but underestimated the 1-year mortality rate of CTD-PAH and IPAH patients assessed as having intermediate risk at diagnosis.
INTREPID: single-versusmultiple-inhaler triple therapy for COPD in usual clinical practice
Authors: Halpin David M.G. , Worsley Sally , Ismaila Afisi S. , Beeh Kai-Michael , Midwinter Dawn , Kocks Janwillem W.H. , Irving Elaine , Marin Jose M. , Martin Neil , Tabberer Maggie , Snowise Neil G. , Compton Chris
Published: April 2021

Introduction

Real-world trial data comparing single- with multiple-inhaler triple therapy (MITT) in COPD patients are currently lacking. The effectiveness of once-daily single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) and MITT were compared in usual clinical care.

Methods

INTREPID was a multicentre, randomised, open-label, phase IV effectiveness study comparing FF/UMEC/VI 100/62.5/25 µgviathe ELLIPTA inhaler with a clinician's choice of any approved non-ELLIPTA MITT in usual COPD clinical practice in five European countries. Primary end-point was proportion of COPD Assessment Test (CAT) responders (≥2-unit decrease in CAT score from baseline) at week 24. Secondary end-points in a subpopulation included change from baseline in forced expiratory volume in 1 s (FEV1) and percentage of patients making at least one critical error in inhalation technique at week 24. Safety was also assessed.

Results

3092 patients were included (FF/UMEC/VI n=1545; MITT n=1547). The proportion of CAT responders at week 24 was significantly greater with FF/UMEC/VIversusnon-ELLIPTA MITT (OR 1.31, 95% CI 1.13–1.51; p<0.001) and mean change from baseline in FEV1was significantly greater with FF/UMEC/VI (77 mLversus28 mL; treatment difference 50 mL, 95% CI 26–73 mL; p<0.001). The percentage of patients with at least one critical error in inhalation technique was low in both groups (FF/UMEC/VI 6%; non-ELLIPTA MITT 3%). Safety profiles, including incidence of pneumonia serious adverse events, were similar between treatments.

Conclusions

In a usual clinical care setting, treatment with once-daily single-inhaler FF/UMEC/VI resulted in significantly more patients gaining health status improvement and greater lung function improvementversusnon-ELLIPTA MITT.
scSensitiveGeneDefine: sensitive gene detection in single-cell RNA sequencing data by Shannon entropy
Authors: Chen Zechuan , Yang Zeruo , Yuan Xiaojun , Zhang Xiaoming , Hao Pei
Published: April 2021

Background

Single-cell RNA sequencing (scRNA-seq) is the most widely used technique to obtain gene expression profiles from complex tissues. Cell subsets and developmental states are often identified via differential gene expression patterns. Most of the single-cell tools utilized highly variable genes to annotate cell subsets and states. However, we have discovered that a group of genes, which sensitively respond to environmental stimuli with high coefficients of variation (CV), might impose overwhelming influences on the cell type annotation.

Result

In this research, we developed a method, based on the CV-rank and Shannon entropy, to identify these noise genes, and termed them as “sensitive genes”. To validate the reliability of our methods, we applied our tools in 11 single-cell data sets from different human tissues. The results showed that most of the sensitive genes were enriched pathways related to cellular stress response. Furthermore, we noticed that the unsupervised result was closer to the ground-truth cell labels, after removing the sensitive genes detected by our tools.

Conclusion

Our study revealed the prevalence of stochastic gene expression patterns in most types of cells, compared the differences among cell marker genes, housekeeping genes (HK genes), and sensitive genes, demonstrated the similarities of functions of sensitive genes in various scRNA-seq data sets, and improved the results of unsupervised clustering towards the ground-truth labels. We hope our method would provide new insights into the reduction of data noise in scRNA-seq data analysis and contribute to the development of better scRNA-seq unsupervised clustering algorithms in the future.
Predicting rifampicin resistance mutations in bacterial RNA polymerase subunit beta based on majority consensus
Authors: Ning Qing , Wang Dali , Cheng Fei , Zhong Yuheng , Ding Qi , You Jing
Published: April 2021

Background

Mutations in an enzyme target are one of the most common mechanisms whereby antibiotic resistance arises. Identification of the resistance mutations in bacteria is essential for understanding the structural basis of antibiotic resistance and design of new drugs. However, the traditionally used experimental approaches to identify resistance mutations were usually labor-intensive and costly.

Results

We present a machine learning (ML)-based classifier for predicting rifampicin (Rif) resistance mutations in bacterial RNA Polymerase subunit β (RpoB). A total of 186 mutations were gathered from the literature for developing the classifier, using 80% of the data as the training set and the rest as the test set. The features of the mutated RpoB and their binding energies with Rif were calculated through computational methods, and used as the mutation attributes for modeling. Classifiers based on five ML algorithms, i.e. decision tree, k nearest neighbors, naïve Bayes, probabilistic neural network and support vector machine, were first built, and a majority consensus (MC) approach was then used to obtain a new classifier based on the classifications of the five individual ML algorithms. The MC classifier comprehensively improved the predictive performance, with accuracy, F-measure and AUC of 0.78, 0.83 and 0.81for training set whilst 0.84, 0.87 and 0.83 for test set, respectively.

Conclusion

The MC classifier provides an alternative methodology for rapid identification of resistance mutations in bacteria, which may help with early detection of antibiotic resistance and new drug discovery.
Genome-wide association and transcriptome studies identify candidate genes and pathways for feed conversion ratio in pigs
Authors: Miao Yuanxin , Mei Quanshun , Fu Chuanke , Liao Mingxing , Liu Yan , Xu Xuewen , Li Xinyun , Zhao Shuhong , Xiang Tao
Published: April 2021

Background

The feed conversion ratio (FCR) is an important productive trait that greatly affects profits in the pig industry. Elucidating the genetic mechanisms underpinning FCR may promote more efficient improvement of FCR through artificial selection. In this study, we integrated a genome-wide association study (GWAS) with transcriptome analyses of different tissues in Yorkshire pigs (YY) with the aim of identifying key genes and signalling pathways associated with FCR.

Results

A total of 61 significant single nucleotide polymorphisms (SNPs) were detected by GWAS in YY. All of these SNPs were located on porcine chromosome (SSC) 5, and the covered region was considered a quantitative trait locus (QTL) region for FCR. Some genes distributed around these significant SNPs were considered as candidates for regulating FCR, including TPH2, FAR2, IRAK3, YARS2, GRIP1, FRS2, CNOT2 and TRHDE. According to transcriptome analyses in the hypothalamus, TPH2 exhibits the potential to regulate intestinal motility through serotonergic synapse and oxytocin signalling pathways. In addition, GRIP1 may be involved in glutamatergic and GABAergic signalling pathways, which regulate FCR by affecting appetite in pigs. Moreover, GRIP1, FRS2, CNOT2, and TRHDE may regulate metabolism in various tissues through a thyroid hormone signalling pathway.

Conclusions

Based on the results from GWAS and transcriptome analyses, the TPH2, GRIP1, FRS2, TRHDE, and CNOT2 genes were considered candidate genes for regulating FCR in Yorkshire pigs. These findings improve the understanding of the genetic mechanisms of FCR and may help optimize the design of breeding schemes.
Transcriptome profiling of immune response to Yersinia ruckeri in spleen of rainbow trout (Oncorhynchus mykiss)
Authors: Wang Di , Sun Simeng , Li Shaowu , Lu Tongyan , Shi Dongfang
Published: April 2021

Background

Yersinia ruckeri is a pathogen that can cause enteric redmouth disease in salmonid species, damaging global production of economically important fish including rainbow trout (Oncorhynchus mykiss). Herein, we conducted the transcriptomic profiling of spleen samples from rainbow trout at 24 h post-Y. ruckeri infection via RNA-seq in an effort to more fully understand their immunological responses.

Results

We identified 2498 differentially expressed genes (DEGs), of which 2083 and 415 were up- and down-regulated, respectively. We then conducted a more in-depth assessment of 78 DEGs associated with the immune system including CCR9, CXCL11, IL-1β, CARD9, IFN, TNF, CASP8, NF-κB, NOD1, TLR8α2, HSP90, and MAPK11, revealing these genes to be associated with 20 different immunological KEGG pathways including the Cytokine-cytokine receptor interaction, Toll-like receptor signaling, RIG-I-like receptor signaling, NOD-like receptor signaling, and MAPK signaling pathways. Additionally, the differential expression of 8 of these DEGs was validated by a qRT-PCR approach and their immunological importance was then discussed.

Conclusions

Our findings provide preliminary insight on molecular mechanism underlying the immune responses of rainbow trout following Y. ruckeri infection and the base for future studies of host-pathogen interactions in rainbow trout.
Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs during replication of Marek’s disease virus in vitro
Authors: Sun Aijun , Zhu Xiaojing , Liu Ying , Wang Rui , Yang Shuaikang , Teng Man , Zheng Luping , Luo Jun , Zhang Gaiping , Zhuang Guoqing
Published: April 2021

Background

The newly discovered reversible N6-methyladenosine (m6A) modification plays an important regulatory role in gene expression. Long non-coding RNAs (lncRNAs) participate in Marek’s disease virus (MDV) replication but how m6A modifications in lncRNAs are affected during MDV infection is currently unknown. Herein, we profiled the transcriptome-wide m6A modification in lncRNAs in MDV-infected chicken embryo fibroblast (CEF) cells.

Results

Methylated RNA immunoprecipitation sequencing results revealed that the lncRNA m6A modification is highly conserved with MDV infection increasing the expression of lncRNA m6A modified sites compared to uninfected cell controls. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that lncRNA m6A modifications were highly associated with signaling pathways associated with MDV infection.

Conclusions

In this study, the alterations seen in transcriptome-wide m6A occurring in lncRNAs following MDV-infection suggest this process plays important regulatory roles during MDV replication. We report for the first time profiling of the alterations in transcriptome-wide m6A modification in lncRNAs of MDV-infected CEF cells.
Gut microbiota in Immunoglobulin A Nephropathy: a Malaysian Perspective
Authors: Sugurmar Agni Nhirmal Kumar , Mohd Rozita , Shah Shamsul Azhar , Neoh Hui-min , Cader Rizna Abdul
Published: April 2021

Introduction

The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort.

Methods

A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota.

Results

Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1–92.2) mls/min/1.73m2 with median remission of 7 years were analysed and compared with 12 healthy controls (4 male; 8 female) with the mean age of 46.5 ± 13.5 years and eGFR of 86.5 (74.2–93.7) mls/min/1.73m2. Other demographic and laboratory parameters such as gender, ethnicity, body mass index (BMI), haemoglobin, serum urea and serum albumin were comparable between the two groups. There were no significant differences seen in the Operational Taxonomic Unit (OTU) and alpha diversity (Shannon index) between IgAN and healthy controls. Alpha diversity increased with increasing CKD stage (p = 0.025). Firmicutes/Bacteroidetes (F/B) ratio was low in both IgAN and healthy cohort. Fusobacteria phylum was significantly increased (p = 0.005) whereas Euryarchaoeota phylum was reduced (p = 0.016) in the IgAN group as compared to the control cohort.

Conclusion

Although we found no differences in OTU and alpha diversity between IgAN in remission and control cohort, there were some differences between the two groups at phylum level.
Renal outcomes of idiopathic and atypical membranous nephropathy in adult Chinese patients: a single center retrospective cohort study
Authors: Jiang Zhenbin , Cai Meishun , Dong Bao , Yan Yu , Wang Yina , Li Xin , Shao Chunying , Zuo Li
Published: April 2021

Background

Membranous nephropathy (MN) is mainly classified into idiopathic MN (iMN) and secondary MN in etiology. In recent years, a new kind of membranous nephropathy, atypical membranous nephropathy (aMN) which shows “full house” in immunofluorescence but without definite etiology was paid more attention. In a single center cohort, the renal outcomes of iMN and aMN were compared.

Methods

iMN and aMN patients were selected from renal pathology databank from January 2006 to December 2015. Patients’ demographics, laboratory values, induction regimens and patients’ responses were recorded. Specially, creatinine, eGFR, albumin and 24 h urinary protein excretion were recorded at 6th month after the induction of immunosuppressive (IS) treatment and at the end of follow up. Complete proteinuria remission was defined as urinary protein < 0.3 g/d, partial proteinuria remission was defined as urinary protein between 0.3 g/d ~ 3.5 g/d and decreased > 50 % from the baseline. The primary outcome was worsening renal function, defined as a 30 % or more decrease in eGFR or end-stage renal disease (eGFR < 15ml/min/1.73m2). COX proportional hazard models were used to test if aMN was a risk factor of worsening renal function compared with iMN.

Results

There were 298 patients diagnosed with MN and followed in our center for 1 year or more, including 145 iMN patients with an average follow-up time of 4.5 ± 2.6 years, and 153 aMN patients with 4.1 ± 2.0 years (p = 0.109). The average age of iMN patients was older than aMN patients (56.1 ± 12.2 versus 47.2 ± 16.2 years old, p < 0.001). There were 99 iMN patients and 105 aMN patients with nephrotic range proteinuria and without previous immunosuppressive treatment. 93 (93.9 %) and 95 (90.5 %) patients underwent immunosuppressive treatment in iMN and aMN group, and there was no significant difference of the overall proteinuria remission rates at 6th month (59.1 % vs. 52.0 %, p = 0.334) and endpoint (73.7 % vs. 69.5 %, p = 0.505) between the two groups. 25 (25.3 %) patients in iMN group and 21 (20.0 %) patients in aMN group reached primary endpoint (X2 = 0.056, p = 0.812). Multivariate COX regression showed that after demographics, baseline laboratory values and remission status at 6th month were adjusted, aMN group had similar renal outcome compared with iMN group, the HR of primary outcome was 0.735 (95 % CI 0.360 ~ 1.503, p = 0.399).

Conclusions

The proteinuria remission rates and renal outcomes were similar in iMN and aMN patients after covariables were adjusted.