bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative leadership and the pitfalls of hierarchy: When formalization enables power to be tamed
Authors: Grégoire Maud , Delalieux Guillaume , Fatien Pauline
Published: September 2022

Hierarchy is a key – but under-studied – lens for critically exploring leadership. The critical literature suggests that both mainstream and alternative leadership contribute to the perpetuation of hierarchy. In mainstream leadership, even in its most recent forms in allegedly ‘flattened’ organizations, hierarchy continues to exist and followers often remain disempowered. In alternative leadership, which occurs for instance in non-hierarchical organizations, an unofficial hierarchy tends to persist: even when leadership is rejected, it is enacted in less-formalized forms, resulting in the tyranny of structurelessness and the undermining of horizontal democratic practices. Our research therefore explores whether and how alternative leadership can be practiced in such a way that it avoids the pitfalls of formal or informal hierarchy. We conducted an in-depth case study of a non-hierarchical group of freelancers, combining 140h of participant observation, 15 semi-structured interviews, and documentary analysis. Our research shows that it is possible to practice alternative leadership in a way that avoids the pitfalls of hierarchy and that this happens through the formalization of leadership. Leadership formalization allows power to be tamed by making it visible but it also involves some tensions.
Expanding tubular microvessels on stiff substrates with endothelial cells and pericytes from the same adult tissue
Authors: Song Xiuyue , Yu Yali , Leng Yu , Ma Lei , Mu Jie , Wang Zihan , Xu Yalan , Zhu Hai , Qiu Xuefeng , Li Peifeng , Li Jing , Wang Dong
Published: September 2022

Endothelial cells (ECs) usually form a monolayer on two-dimensional (2D) stiff substrates and a tubular structure with soft hydrogels. The coculture models using ECs and pericytes derived from different adult tissues or pluripotent stem cells cannot mimic tissue-specific microvessels due to vascular heterogeneity. Our study established a method for expanding tubular microvessels on 2D stiff substrates with ECs and pericytes from the same adult tissue. We isolated microvessels from adult rat subcutaneous soft connective tissue and cultured them in the custom-made tubular microvascular growth medium on 2D stiff substrates (TGM2D). TGM2D promoted adult microvessel growth for at least 4 weeks and maintained a tubular morphology, contrary to the EC monolayer in the commercial medium EGM2MV. Transcriptomic analysis showed that TGM2D upregulated angiogenesis and vascular morphogenesis while suppressing oxidation and lipid metabolic pathways. Our method can be applied to other organs for expanding organ-specific microvessels for tissue engineering.
Modelling variance in the multidimensional Health Literacy Questionnaire: Does a General Health Literacy factor account for observed interscale correlations?
Authors: Elsworth Gerald R , Nolte Sandra , Cheng Christina , Hawkins Melanie , Osborne Richard H
Published: September 2022

Objectives:

Self-report measures of health literacy frequently encompass a group of conceptually distinct but related domains scored as either a single scale or separately for each domain. Psychometric studies of the 44-item Health Literacy Questionnaire, scored as nine separate scales, typically report the results of correlated factors confirmatory factor analyses as validity evidence. However, some scales are quite strongly correlated, raising the question of whether there is sufficient discriminant validity to warrant separate scoring. This psychometric study aims to contrast the results of fitting higher-order and bifactor models as alternative options to illuminate the issue.

Methods:

Correlated factors, higher-order and bifactor confirmatory factor analysis models were fitted to an Australian sample of responses to the Health Literacy Questionnaire (N = 813) using Bayesian confirmatory factor analysis methods.

Results:

All models representing a nine-factor structure for the Health Literacy Questionnaire fitted well. The correlated factors model replicated previous findings, showing inter-factor correlations between 0.19 and 0.93. A higher-order model showed relatively high loadings of all nine first-order factors on the second-order factor with particularly high loadings (⩾0.97) for three. Two bifactor models showed that the majority of Health Literacy Questionnaire items were multifactorial, each containing systematic variance from both a General Health Literacy factor and a domain-specific factor. Seven items from four scales were identified as strongly associated with the General Health Literacy factor, with item content suggesting that this factor indexes a broad sense of agency and efficacy in interacting with health-related information and healthcare providers.

Conclusion:

Contrasting correlated factors, higher-order and bifactor models fitted to the Health Literacy Questionnaire suggest that constituent items in self-report health literacy questionnaires might be anticipated to represent at least two sources of reliable and substantive common factor variance: variance associated with General Health Literacy and variance associated with a more specific domain, suggesting that items may be ‘irreducibly’ heterogeneous. Implications for test development and validation practice are discussed.
Perception of E-health Technology Scale in Chinese Brief (PETS-C Brief): Translation, item reduction, and psychometric testing
Authors: Kwan Rick Yiu Cho , Lam Simon Ching , Wang Shao Ling , Wong Arkers Kwan Ching , Shi Lei , Wong Frances Kam Yuet
Published: September 2022

Introduction

Perception of e-health is a broad concept involving many aspects of values and thoughts related to e-health. It is an important precursor to using e-health technologies to promote health. The purpose of this study is to validate an instrument for measuring perceptions of e-health technology among healthcare professionals.

Methods

This methodological study was conducted in China. We based on an existing instrument to develop a new instrument (i.e. PETS-C Brief). In phase 1, we modified and translated the existing instrument into Chinese. Subsequently, we employed the modified and translated instrument to conduct a cross-sectional survey. In phase 2, we randomly selected data from 400 participants to run an exploratory factor analysis and item analysis to reduce the number of items and develop factors. In phase 3, we employed the data from the remaining participants to run a confirmatory factor analysis to confirm the instrument structure.

Results

In phase 1, the modified and translated instrument showed good content and face validities (S-CVI = 0.96, mean comprehensibility = 93.5%). 1338 participants completed the survey. In phase 2, the number of items was reduced from 40 to 19, which demonstrated a 4-factor model. In phase 3, the goodness-of-fit of the 4-factor PETS-C Brief was shown to be acceptable (χ2/d.f. = 6.40, CFI = 0.93, RMR = 0.40, NFI = 0.92, RMSEA = 0.076, IFI = 0.93).

Discussion

This study suggests using this instrument to survey perceptions of e-health technology in Chinese people. Future studies should examine its other important psychometric properties, including convergent/discriminant and predictive validity on behaviors using e-health technology.
Associations Between Low-Household Income and First-Generation Status With College Student Belonging, Mental Health, and Well-Being
Authors: Kreniske Philip , Mellins Claude A. , Shea Eileen , Walsh Kate , Wall Melanie , Santelli John S. , Reardon Leigh , Khan Shamus , Hwei Tse , Hirsch Jennifer S.
Published: September 2022

Entering college is recognized as a developmental milestone. Completing college is difficult, however, and students who are first-generation (FG) or low-income (LI) or both (FGLI) encounter unique challenges. In secondary analysis of data from a population-based survey ( N=1671 undergraduates) at two interconnected highly-selective institutions of higher education, we examined belonging, mental health, and well-being comparing the overall student body to FG, LI, and FGLI students. Most FG, LI, and FGLI students reported a strong sense of belonging, few mental health symptoms, and good general health and well-being. Compared to the overall student body, FG, LI and FGLI students reported lower levels of perceived family support, worse sleep quality, and worked more hours for pay; FG and FGLI students reported higher symptoms of depression; LI and FGLI reported less hazardous drinking. Interventions and programmatic changes at the institutional level are needed to build campuses where students of all backgrounds can thrive.
Fair Allocations in an Overlapping Generations Economy
Authors: Dubey Ram Sewak , Ruscitti Francesco
Published: September 2022

This paper investigates fair (i.e., envy-free and efficient) allocations in an overlapping generations economy without production and with two-period lived agents. We show that there is a conflict between no-envy and efficiency when all generations have identical preferences. This conflict crucially depends on the size of the given young age consumption of the initial old generation relative to the young age consumption at the golden-rule. We then show that there exist non-stationary preferences for which such a conflict does not arise, regardless of the young age consumption of the initial old generation.

JEL Classifications: D60, D63, D70
Predictors Using Machine Learning of Complete Peroneal Nerve Palsy Recovery After Multiligamentous Knee Injury: A Multicenter Retrospective Cohort Study
Authors: Vasavada Kinjal , Shankar Dhruv S. , Bi Andrew S. , Moran Jay , Petrera Massimo , Kahan Joseph , Alaia Erin F. , Medvecky Michael J. , Alaia Michael J.
Published: September 2022

Background:

Peroneal nerve (PN) palsy is one of the most debilitating sequelae of multiligamentous knee injuries (MLKIs). There is limited research on recovery from complete PN palsy.

Purpose/Hypothesis:

The purpose of this study was to characterize PN injuries and develop a predictive model of complete PN recovery after MLKI using machine learning. It was hypothesized that elevated body mass index (BMI) would be predictive of lower likelihood of recovery.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

The authors conducted a retrospective review of patients seen at 2 urban hospital systems for treatment of MLKI with associated complete PN palsy, defined as the presence of complete foot drop with or without sensory deficits on physical examination. Recovery was defined as the complete resolution of foot drop. A random forest (RF) classifier algorithm was used to identify demographic, injury, treatment, and postoperative variables that were significant predictors of recovery from complete PN palsy. Validity of the RF model was assessed using overall accuracy, F1 score, and area under the receiver operating characteristic curve (AUC).

Results:

Overall, 16 patients with MLKI with associated complete PN palsy were included in the cohort. Among them, 75% (12/16) had documented knee dislocation requiring reduction. Complete recovery occurred in 4 patients (25%). Nerve contusions on magnetic resonance imaging were more common among patients without PN recovery, but there were no other significant differences between recovery and nonrecovery groups. The RF model found that older age, increasing BMI, and male sex were predictive of worse likelihood of PN recovery. The model was found to have good validity, with a classification accuracy of 75%, F1 score of 0.86, and AUC of 0.64.

Conclusion:

The RF model in this study found that increasing age, BMI, and male sex were predictive of decreased likelihood of nerve recovery. While further study of machine learning models with larger patient data sets is required to identify the most superior model, these findings present an opportunity for orthopaedic surgeons to better identify, counsel, and treat patients with MLKIs and concomitant complete PN palsy.
Robust and Efficient Online Auditory Psychophysics
Authors: Zhao Sijia , Brown Christopher A. , Holt Lori L. , Dick Frederic
Published: September 2022

Most human auditory psychophysics research has historically been conducted in carefully controlled environments with calibrated audio equipment, and over potentially hours of repetitive testing with expert listeners. Here, we operationally define such conditions as having high ‘auditory hygiene’. From this perspective, conducting auditory psychophysical paradigms online presents a serious challenge, in that results may hinge on absolute sound presentation level, reliably estimated perceptual thresholds, low and controlled background noise levels, and sustained motivation and attention. We introduce a set of procedures that address these challenges and facilitate auditory hygiene for online auditory psychophysics. First, we establish a simple means of setting sound presentation levels. Across a set of four level-setting conditions conducted in person, we demonstrate the stability and robustness of this level setting procedure in open air and controlled settings. Second, we test participants’ tone-in-noise thresholds using widely adopted online experiment platforms and demonstrate that reliable threshold estimates can be derived online in approximately one minute of testing. Third, using these level and threshold setting procedures to establish participant-specific stimulus conditions, we show that an online implementation of the classic probe-signal paradigm can be used to demonstrate frequency-selective attention on an individual-participant basis, using a third of the trials used in recent in-lab experiments. Finally, we show how threshold and attentional measures relate to well-validated assays of online participants’ in-task motivation, fatigue, and confidence. This demonstrates the promise of online auditory psychophysics for addressing new auditory perception and neuroscience questions quickly, efficiently, and with more diverse samples. Code for the tests is publicly available through Pavlovia and Gorilla.
Assessment of total pain in people in oncologic palliative care: integrative literature review
Authors: Gomes-Ferraz Cristiane Aparecida , Rezende Gabriela , Fagundes Amanda Antunes , De Carlo Marysia Mara Rodrigues do Prado
Published: September 2022

The promotion of comfort and quality of life of people with cancer in palliative care requires flawless evaluation and management of pain, understood in its multidimensionality and integrality. The objective of this study was to present an overview of the scientific production referring to evaluation of the pain and total pain of patients with advanced cancer in palliative care. The study involved an integrative literature review, searching the databases PubMed, Embase, Cinahl, Lilacs and Web of Science using the descriptors ‘Total Pain’, ‘Cancer Pain’, ‘Pain’, ‘Symptom Assessment’, ‘Pain Measurement’, ‘Pain Evaluation’, ‘Neoplasms’, ‘Cancer’, ‘Tumor’, ‘Palliative Care’, ‘Hospice Care’, and ‘Terminal Care’. To select the studies, the authors used the reference manager Mendeley and the application Rayyan™, as well as blind and independent peer review. Twenty-two articles were selected, published between 2002 and 2020 in different countries, and classified into two thematic units: ‘Physical, social, emotional, and spiritual factors related to pain in cancer’ ( N = 13) and ‘Importance of the overall evaluation and multidisciplinary team in the management of pain’ ( N = 9). Advanced cancer is associated with high mortality, a decline in health status, the presence of pain, and complex psychosocial concerns. Pain and symptoms in patients in palliative care should be evaluated as a whole and controlled thorough the work of an interdisciplinary team. The qualitative synthesis of the results demonstrates that most of the evaluated studies have a mixed nature; there are significant methodological differences among them and a low level of evidence in studies relating to the subject of pain evaluation in palliative care.
POEM Controversies: State of the Art and Science
Authors: Yang Dennis , Draganov Peter V.
Published: September 2022

Per-oral endoscopic myotomy (POEM) has become part of the standard of care for achalasia around the world. Although multiple studies have consistently demonstrated excellent short to mid-term clinical efficacy and safety profile, several questions remain, including how long term clinical outcomes, optimal POEM technique, and measures to reduce post-procedural reflux without compromising clinical efficacy. In this section, we provide an overview of some of the current challenges and comment on future directions of POEM as a therapy for esophageal motility disorders.
Oral Microbiome Diversity Between Patients With Normal Versus Elevated Salivary Pepsin Levels and Its Implication in Gastroesophageal Reflux Disease
Authors: Ma Steven D. , Guccione Caitlin , Linnemeyer Kristen , Weissbrod Philip A. , Curtius Kit , Yadlapati Rena H.
Published: September 2022

This pilot study aimed to assess oral microbiome diversity between patients with and without elevated salivary pepsin concentrations. Over 9 months, 85 enrolled subjects (73 symptomatic patients; 12 asymptomatic volunteers) provided salivary samples off acid suppression. Subjects with elevated pepsin (≥25 ng/mL) had significantly greater Shannon entropy diversity compared to subjects with normal pepsin (<25 ng/mL) on 16S rRNA sequencing ( P = .015), indicating increased oral microbiome biodiversity in patients with elevated salivary pepsin. Repeated gastro-esophageal reflux events from the stomach to the oral cavity may contribute to this observed change in oral microbiome diversity with potential implications in symptom generation and/or therapy.
Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis
Authors: Yang Mingjin , Li Yishi , Jiang Youfan , Guo Shuliang , He Jian-Qing , Sin Don D.
Published: September 2022

Introduction

Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting β2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD.

Methods

Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke.

Results

A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6%versus1.3%; relative risk 1.42, 95% CI 1.11–1.81) and triple therapy (1.6%versus1.4%; relative risk 1.29, 95% CI 1.03–1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power.

Conclusion

Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.
Changes in cardiopulmonary exercise capacity and limitations 3–12 months after COVID-19
Authors: Ingul Charlotte Björk , Edvardsen Anne , Follestad Turid , Trebinjac Divna , Ankerstjerne Odd Andre Wathne , Brønstad Eivind , Rasch-Halvorsen Øystein , Aarli Bernt , Dalen Håvard , Nes Bjarne Martens , Lerum Tøri Vigeland , Einvik Gunnar , Stavem Knut , Skjørten Ingunn
Published: September 2022

Rationale

To describe cardiopulmonary function during exercise 12 months after hospital discharge for coronavirus disease 2019 (COVID-19), assess the change from 3 to 12 months, and compare the results with matched controls without COVID-19.

Methods

In this prospective, longitudinal, multicentre cohort study, hospitalised COVID-19 patients were examined using a cardiopulmonary exercise test (CPET) 3 and 12 months after discharge. At 3 months, 180 performed a successful CPET, and 177 did so at 12 months (mean age 59.3 years, 85 females). The COVID-19 patients were compared with controls without COVID-19 matched for age, sex, body mass index and comorbidity. Main outcome was peak oxygen uptake (V′O2 peak).

Results

Exercise intolerance (V′O2 peak<80% predicted) was observed in 23% of patients at 12 months, related to circulatory (28%), ventilatory (17%) and other limitations including deconditioning and dysfunctional breathing (55%). Estimated mean difference between 3 and 12 months showed significant increases inV′O2 peak% pred (5.0 percentage points (pp), 95% CI 3.1–6.9 pp; p<0.001),V′O2 peak·kg−1% pred (3.4 pp, 95% CI 1.6–5.1 pp; p<0.001) and oxygen pulse % pred (4.6 pp, 95% CI 2.5–6.8 pp; p<0.001).V′O2 peakwas 2440 mL·min−1in COVID-19 patients compared to 2972 mL·min−1in matched controls.

Conclusions

1 year after hospital discharge for COVID-19, the majority (77%), had normal exercise capacity. Only every fourth had exercise intolerance and in these circulatory limiting factors were more common than ventilator factors. Deconditioning was common.V′O2 peakand oxygen pulse improved significantly from 3 months.
Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis
Authors: Cui Feipeng , Sun Yu , Xie Junqing , Li Dankang , Wu Mingyang , Song Lulu , Hu Yonghua , Tian Yaohua
Published: September 2022

Background

Air pollutants are considered as non-negligible risk factors of idiopathic pulmonary fibrosis (IPF). However, the relationship between long-term air pollution and the incidence of IPF is unknown. Our objective was to explore the associations of air pollutants with IPF risk and further assess the modification effect of genetic susceptibility.

Methods

We used land-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx) and particulate matter (fine particulate matter with diameter <2.5 μm (PM2.5) and particulate matter with diameter <10 μm (PM10)). The polygenic risk score (PRS) was constructed using 13 independent single nucleotide polymorphisms. Cox proportional hazard models were used to evaluate the associations of air pollutants with IPF risk and further investigate the modification effect of genetic susceptibility. Additionally, absolute risk was calculated.

Results

Among 433 738 participants from the UK Biobank, the incidence of IPF was 27.45 per 100 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios of IPF for each interquartile range increase in NO2, NOxand PM2.5were 1.11 (95% CI 1.03–1.19), 1.07 (95% CI 1.01–1.13) and 1.09 (95% CI 1.02–1.17), respectively. PM2.5had the highest population attribution risk, followed by NOxand NO2. There were additive interactions between NO2, NOxand PM2.5and genetic susceptibility. Participants with a high PRS and high air pollution had the highest risk of incident IPF compared with those with a low PRS and low air pollution (adjusted hazard ratio: NO23.94 (95% CI 2.77–5.60), NOx3.08 (95% CI 2.21–4.27), PM2.53.65 (95% CI 2.60–5.13) and PM103.23 (95% CI 2.32–4.50)).

Conclusion

Long-term exposures to air pollutants may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.
Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms
Authors: Son Kiho , Jamil Rameen , Chowdhury Abhiroop , Mukherjee Manan , Venegas Carmen , Miyasaki Kate , Zhang Kayla , Patel Zil , Salter Brittany , Yuen Agnes Che Yan , Lau Kevin Soon-Keen , Cowbrough Braeden , Radford Katherine , Huang Chynna , Kjarsgaard Melanie , Dvorkin-Gheva Anna , Smith James , Li Quan-Zhen , Waserman Susan , Ryerson Christopher J , Nair Parameswaran , Ho Terence , Balakrishnan Narayanaswamy , Nazy Ishac , Bowdish Dawn ME , Svenningsen Sarah , Carlsten Chris , Mukherjee Manali
Published: September 2022

Background

Autoimmunity has been reported in patients with severe COVID-19. We investigated whether antinuclear/extractable-nuclear antibodies (ANAs) were present up to a year after infection, and if they were associated with the development of clinically relevant Post-Acute Sequalae of COVID-19 (PASC) symptoms.

Methods

A rapid assessment line immunoassay was used to measure circulating levels of ANA/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6, and 12 months post-recovery. Patient-reported fatigue, cough, and dyspnea were recorded at each timepoint. Multivariable logistic regression model and receiver-operating curves (ROC) were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines.

Results

Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p<0.001). The mean number of ANA autoreactivities per individual decreased from 3 to 12 months (3.99 to 1.55) with persistent positive titers associated with fatigue, dyspnea, and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, AUC=0.86) and dyspnea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNFα) and C-reactive protein predicted the elevated ANAs at 12 months. TNFα, D-dimer, and IL-1β had the strongest association with symptoms at 12 months. Regression analysis showed TNFα predicted fatigue (β=4.65, p=0.004) and general symptomaticity (β=2.40, p=0.03) at 12 months.

Interpretation

Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNFα) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.
Immunophenotypes of anti-SARS-CoV-2 responses associated with fatal COVID-19
Authors: Šelb Julij , Bitežnik Barbara , Bidovec Stojković Urška , Rituper Boštjan , Osolnik Katarina , Kopač Peter , Svetina Petra , Cerk Porenta Kristina , Šifrer Franc , Lorber Petra , Trinkaus Leiler Darinka , Hafner Tomaž , Jerič Tina , Marčun Robert , Lalek Nika , Frelih Nina , Bizjak Mojca , Lombar Rok , Nikolić Vesna , Adamič Katja , Mohorčič Katja , Grm Zupan Sanja , Šarc Irena , Debeljak Jerneja , Koren Ana , Luzar Ajda Demšar , Rijavec Matija , Kern Izidor , Fležar Matjaž , Rozman Aleš , Korošec Peter
Published: September 2022

Background

The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood.

Methods

A longitudinal prospective cohort of hospitalised patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors.

Results

Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod,and the anti-S1-IgGhighTlowBmodNKmodIL-6highesthad a high risk of fatal COVID-19 (HR 3.36–21.69; 95% CI 1.51–163.61 and HR 8.39–10.79; 95% CI 1.20–82.67; p≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6modand anti-S1-IgGlowThighestBhighestNKhighestIL-6lowcluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgGhighThighBmodNKmodIL-6lowand anti-S1-IgGhighestThighestBhighNKhighIL-6lowestclusters were characterised by a very low risk of mortality.

Conclusions

By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.
Improving the wellbeing of caregivers of patients with COPD using a home-based pulmonary rehabilitation programme
Authors: Grosbois Jean-Marie , Gephine Sarah , Kyheng Maeva , Le Rouzic Olivier , Chenivesse Cécile
Published: September 2022

Objectives

The aim of this study was to evaluate the effects of a home-based pulmonary rehabilitation (PR) programme on anxiety and depressive symptoms, general fatigue and burden in informal caregivers of patients with COPD. We also evaluated the baseline characteristics of both patients and caregivers that contributed to the change in caregiver's outcomes after PR.

Methods

In this retrospective study, patients with COPD were referred to an 8-week home-based PR programme consisting of a weekly supervised 90-min session. Informal caregivers were invited to participate in PR according to the patient's preference and its availability. Caregivers received educational support, behavioural therapies and self-management strategies using the same methods as for patients. Burden, anxiety and depressive symptoms, and general fatigue of caregivers were assessed at baseline and at the end of PR.

Results

241 patients with COPD and 138 (57.3%) caregivers were included. The majority of the caregivers were women (70.5%) and spouses (90.3%) and had at least three comorbidities (57.3%). A large proportion of caregivers showed baseline high burden, anxiety symptoms and abnormal fatigue (40%, 40% and 45%, respectively). Burden, anxiety and depressive symptoms, and general fatigue of informal caregivers were all improved after PR (p<0.05). Long-term oxygen therapy and/or noninvasive ventilation, coronaropathy and/or peripheral arterial disease and a higher baseline modified Medical Research Council Dyspnoea scale score in patients with COPD were associated with a decrease in caregiver's burden after PR.

Conclusion

A large proportion of caregivers of patients with COPD showed anxiety symptoms, fatigue and a high burden. These outcomes were improved by integrating the caregiver into a home-based PR programme.
Global burden of nontuberculous mycobacteria in the cystic fibrosis population: a systematic review and meta-analysis
Authors: Prieto Miguel D. , Alam Mosaab E. , Franciosi Alessandro N. , Quon Bradley S.
Published: September 2022

Background

People living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We conducted a systematic review of the literature to estimate the burden (prevalence and incidence) of NTM in the cystic fibrosis population.

Methods

Electronic databases, registries and grey literature sources were searched for cohort and cross-sectional studies reporting epidemiological measures (incidence and prevalence) of NTM infection or NTM pulmonary disease in cystic fibrosis. The last search was conducted in September 2021; we included reports published since database creation and registry reports published since 2010. The methodological quality of studies was appraised with the Joanna Briggs Institute tool. A random effects meta-analysis was conducted to summarise the prevalence of NTM infection, and the remaining results are presented in a narrative synthesis.

Results

This review included 95 studies. All 95 studies reported on NTM infection, and 14 of these also reported on NTM pulmonary disease. The pooled estimate for the point prevalence of NTM infection was 7.9% (95% CI 5.1–12.0%). In meta-regression, sample size and geographical location of the study modified the estimate. Longitudinal analysis of registry reports showed an increasing trend in NTM infection prevalence between 2010 and 2019.

Conclusions

The overall prevalence of NTM infection in cystic fibrosis is 7.9% and is increasing over time based on international registry reports. Future studies should report screening frequency, microbial identification methods and incidence rates of progression from NTM infection to pulmonary disease.
PACS-2 deficiency in tubular cells aggravates lipid-related kidney injury in diabetic kidney disease
Authors: Zhao Chanyue , Li Li , Li Chenrui , Tang Chengyuan , Cai Juan , Liu Yu , Yang Jinfei , Xi Yiyun , Yang Ming , Jiang Na , Han Yachun , Liu Yan , Luo Shilu , Xiao Li , Sun Lin
Published: September 2022

Background

Lipid accumulation in tubular cells plays a key role in diabetic kidney disease (DKD). Targeting lipid metabolism disorders has clinical value in delaying the progression of DKD, but the precise mechanism by which molecules mediate lipid-related kidney injury remains unclear. Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional sorting protein that plays a role in lipid metabolism. This study determined the role of PACS-2 in lipid-related kidney injury in DKD.

Methods

Diabetes was induced by a high-fat diet combined with intraperitoneal injections of streptozotocin (HFD/STZ) in proximal tubule-specific knockout of Pacs-2 mice (PT-Pacs-2−/− mice) and the control mice (Pacs-2fl/fl mice). Transcriptomic analysis was performed between Pacs-2fl/fl mice and PT-Pacs-2−/− mice.

Results

Diabetic PT-Pacs-2−/− mice developed more severe tubule injury and proteinuria compared to diabetic Pacs-2fl/fl mice, which accompanied with increasing lipid synthesis, uptake and decreasing cholesterol efflux as well as lipid accumulation in tubules of the kidney. Furthermore, transcriptome analysis showed that the mRNA level of sterol O-acyltransferase 1 (Soat1) was up-regulated in the kidney of control PT-Pacs-2−/− mice. Transfection of HK2 cells with PACS-2 siRNA under high glucose plus palmitic acid (HGPA) condition aggravated lipid deposition and increased the expression of SOAT1 and sterol regulatory element-binding proteins (SREBPs), while the effect was blocked partially in that of co-transfection of SOAT1 siRNA.

Conclusions

PACS-2 has a protective role against lipid-related kidney injury in DKD through SOAT1/SREBPs signaling.
Targeting miR-21 in spinal cord injuries: a game-changer?
Authors: Malvandi Amir Mohammad , Rastegar-moghaddam Seyed Hamidreza , Ebrahimzadeh-Bideskan Saeede , Lombardi Giovanni , Ebrahimzadeh-Bideskan Alireza , Mohammadipour Abbas
Published: September 2022

Spinal cord injury (SCI) is a devastating neurological state causing physical disability, psychological stress and financial burden. SCI global rate is estimated between 250,000 and 500,000 individuals every year, of which 60% of victims are young, healthy males between 15 and 35 years. A variety of pathological conditions such as neuroinflammation, mitochondrial dysfunction, apoptosis, glial scar formation, blood-spinal cord barrier disruption, and angiogenesis disruption occur after SCI leading to a limitation in recovery. MicroRNAs (miRs) are endogenous and non-coding RNAs consisting of 22 nucleotides that regulate 60% of all human genes and involve several normal physiological processes and pathological conditions. miR-21 is among the most highly expressed miRs and its expression has been shown to increase one day after SCI and this elevation is sustained up to 28 days after injury. Overexpression of miR-21 exerts many protective effects against SCI by inhibiting neuroinflammation, improving blood-spinal cord barrier function, regulating angiogenesis, and controlling glial scar formation. It also exhibits anti-apoptotic effects in SCI by down-regulating the expression of PTEN, Spry2, and PDCD4. This review provides a novel therapeutic perspective for miR-21 in SCI.
Reconstruction and analysis of potential biomarkers for hypertrophic cardiomyopathy based on a competing endogenous RNA network
Authors: Chen Jin-yan , Xie Zhang-xin , Dai Jia-zhen , Han Jun-yong , Wang Kun , Lu Li-hong , Jin Jing-jun , Xue Shi-jie
Published: September 2022

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA–miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA–mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM.
Long-segment spinal cord infarction complicated with multiple cerebral infarctions: a case report
Authors: Xing Weifang , Zhang Wensheng , Ma Guozhong , Ma Guofen , He Jinzhao
Published: September 2022

Background

Spinal cord infarction is a rare disorder, constituting only 1% to 2% of all neurological vascular emergencies (making it less frequent than ischaemic brain injury); however, it is severe. A case of long-segment spinal cord infarction complicated with multiple cerebral infarctions has not been reported to date.

Case presentation

Here, we describe one such case: a patient with spinal cord infarction from the cervical 7 (C7) to thoracic 6 (T6) vertebrae, along with anterior spinal artery syndrome and complicated by multiple cerebral infarctions. A 65-year-old farmer experienced sudden onset of severe pain in his chest, back and upper limbs while unloading heavy objects. Subsequently, both his lower limbs became weak and hypoaesthetic, and he was unable to walk. Spinal magnetic resonance imaging (MRI) revealed equal T1 and long T2 signals centred on the anterior horn of the spinal cord. The axial slice of these signals was shaped like an owl’s eye. After receiving drug treatment and active rehabilitation treatment, the patient’s ability to walk was restored.

Conclusions

Long-segment spinal cord infarction is rare and can be complicated with cerebral infarction. The specific aetiology is worth exploring.
Factors associated with duration of breastfeeding in women giving birth for the first time
Authors: Haas David M. , Yang Ziyi , Parker Corette B. , Chung Judith , Parry Samuel , Grobman William A. , Mercer Brian M. , Simhan Hyagriv N. , Silver Robert M. , Wapner Ronald J. , Saade George R. , Greenland Philip , Merz Noel Bairey , Reddy Uma M. , Pemberton Victoria L. ,   for the nuMoM2b study and the nuMoM2b Heart Health Study
Published: September 2022

Objective

To examine maternal, psychosocial, and pregnancy factors associated with breastfeeding for at least 6 months in those giving birth for the first time.

Methods

We performed a planned secondary analysis of an observational cohort study of 5249 women giving birth for the first time. Women were contacted at least 6 months after delivery and provided information regarding breastfeeding initiation, duration, and exclusivity. Maternal demographics, psychosocial measures, and delivery methods were compared by breastfeeding groups.

Results

4712 (89.8%) of the women breastfed at some point, with 2739 (58.2%) breastfeeding for at least 6 months. Of those who breastfed, 1161 (24.7% of the entire cohort), breastfed exclusively for at least 6 months. In the multivariable model among those who ever breastfed, not smoking in the month prior to delivery (adjusted odds ratio [aOR] 2.04, 95%CI 1.19–3.45), having a Master’s degree of higher (aOR 1.89, 95%CI 1.51–2.36), having a planned pregnancy (aOR 1.48, 95%CI 1.27–1.73), older age (aOR 1.02, 95% CI, 1.01–1.04), lower BMI (aOR 0.96 95% CI 0.95–0.97), and having less anxiety measured during pregnancy (aOR 0.990, 95%CI 0.983–0.998) were associated with breastfeeding for at least 6 months. Compared to non-Hispanic White women, Hispanic women, while being more likely to breastfeed initially (aOR 1.40, 95%CI 1.02–1.92), were less likely to breastfeed for 6 months (aOR 0.72, 95%CI 0.59–0.88). While non-Hispanic Black women were less likely than non-Hispanic White women to initiate breastfeeding (aOR 0.68, 95%CI 0.51–0.90), the odds of non-Hispanic Black women of continuing to breastfeed for at least 6 months was similar to non-Hispanic White women (aOR 0.92, 95%CI 0.71–1.19).

Conclusions

In this cohort of women giving birth for the first time, duration of breastfeeding was associated with several characteristics which highlight groups at greater risk of not breastfeeding as long as currently recommended.

Trial registration

NCT01322529 (nuMoM2b) and NCT02231398 (nuMoM2b-Heart Health)
Preventing adverse events of chemotherapy for gastrointestinal cancer by educating patients about the nocebo effect: a randomized-controlled trial
Authors: Michnevich T. , Pan Y. , Hendi A. , Oechsle K. , Stein A. , Nestoriuc Y.
Published: September 2022

Background

Adverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events.

Methods

In this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms.

Results

General linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [− 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy.

Conclusions

This study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events.

Trial registration

Retrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).
Long-term treatment patterns and survival in metastatic breast cancer by intrinsic subtypes – an observational cohort study in Sweden
Authors: Lindman Henrik , Wiklund Fredrik , Andersen Klaus Kaae
Published: September 2022

Background

Longitudinal, real-world data on the management of metastatic breast cancer is increasingly relevant to understand breast cancer care in routine clinical practice. Yet such data are scarce, particularly beyond second- and third-line treatment strategies. This study, therefore, examined both the long-term treatment patterns and overall survival (OS) in a regional Swedish cohort of female patients with metastatic breast cancer stratified by subtype in routine clinical practice during a recent eight-year period and correlation to current treatment guidelines.

Methods

Consecutive female patients with metastatic breast cancer  clinically managed at Uppsala University Hospital, Uppsala, Sweden, during 2009–2016 and followed until the end of September, 2017 (n = 370) were included and, where possible, classified as having one of five, intrinsic subtypes: Luminal A; Luminal B; human epidermal growth factor receptor 2-positive (HER2+)/ estrogen receptor-positive (ER+); HER2+/estrogen receptor-negative (ER-); or triple negative breast cancer (TNBC). Treatment patterns and OS were estimated by subtype using time-to-event methods.

Results

A total of 352/370 patients with metastatic breast cancer (mean age 67.6 years) could be subtyped: 118 (34%) were Luminal A, 119 (34%) Luminal B, 31 (8%) HER2+/ER-, 38 (11%) HER2+/Luminal, and 46 (13%) TNBC. The median number of metastatic treatment lines was 3. Most patients were on active treatment during follow-up (80% of the observation period), except for patients with TNBC who were on treatment for 60% of the observation time. Overall, 67% of patients died whilst on treatment. Among all patients (n = 370), median OS was 32.5 months (95% CI = 28.2–35.7). The 5-year survival rate was highest for HER2+/Luminal (46%) patients, followed by Luminal B (29%), Luminal A (28%), HER2+/ER- (21%), and TNBC (7%). Increasing age and number of metastatic sites also predicted worse survival.

Conclusions

Metastatic breast cancer patients in Sweden, irrespective of subtype, generally receive active treatment until time of death. Survival varies considerably across subtypes and is also associated with patient characteristics. Regardless of differences in treatment patterns for Luminal A and B patients, long-term OS was the same.