bluuebunny/crossref_metadata_2025 huggingface dataset:
Delay in seeking medical help in patients with rheumatoid arthritis in India: A qualitative study
Authors: Jain Avinash , Aggarwal Amita , Adams Jo , Jordan Rachel E. , Sadhra Steven , Dubey Shirish , Allen Kerry , Kumar Kanta
Published: October 2020

Background

Rheumatoid arthritis (RA) is an autoimmune disease with varied articular and extra‐articular manifestations. In developing countries such as India patients with RA often delay seeking medical advice which may impact prognosis and disease burden.

Aim

To explore perceptions and experiences of patients living in India in seeking medical help for their RA symptoms.

Methods

Clinician‐diagnosed RA participants from different socioeconomic backgrounds were interviewed using a semi‐structured topic guide. Participants were purposively selected and interviewed following an iterative approach. All interviews were recorded and transcribed by an independent company and analyzed using a thematic framework. Findings were reported in accordance with consolidated criteria for reporting qualitative research guidelines.

Results

Twenty participants (13 male, 7 female) with median age 40 years (35.7‐46.5) were recruited. Three overarching themes demonstrating participants’ experiences and reasons for delay in seeking medical help were identified. (1) “Symptoms perspectives and delay in participants’ journey” narrated participants’ experiences of having RA symptoms, how these were perceived, rationalized and led to delay. (2) “Participants’ experience of the healthcare system” illustrated delay in referral, reaching diagnosis and treatment initiation highlighting their experiences with the health system. (3) “Recommendations for improving care” where participants made recommendations for reducing the delay at local and national levels.

Conclusion

This is the first qualitative study which explored perceptions and experiences of RA patients in India resulting in delay. Improved provision of rheumatology care, effective referral system and greater involvement of government at local and national levels are needed to improve the delay in seeking medical help for Indian patients.
Quantifying the impact of an inference model in Bayesian phylogenetics
Authors: Bilderbeek Richèl J. C. , Laudanno Giovanni , Etienne Rampal S.
Published: October 2020

Phylogenetic trees are currently routinely reconstructed from an alignment of character sequences (usually nucleotide sequences). Bayesian tools, such as MrBayes, RevBayes and BEAST2, have gained much popularity over the last decade, as they allow joint estimation of the posterior distribution of the phylogenetic trees and the parameters of the underlying inference model. An important ingredient of these Bayesian approaches is the species tree prior. In principle, the Bayesian framework allows for comparing different tree priors, which may elucidate the macroevolutionary processes underlying the species tree. In practice, however, only macroevolutionary models that allow for fast computation of the prior probability are used. The question is how accurate the tree estimation is when the real macroevolutionary processes are substantially different from those assumed in the tree prior.

Here we present pirouette, a free and open‐source r package that assesses the inference error made by Bayesian phylogenetics for a given macroevolutionary diversification model. pirouette makes use of BEAST2, but its philosophy applies to any Bayesian phylogenetic inference tool.

We describe pirouette’s usage providing full examples in which we interrogate a model for its power to describe another.

Last, we discuss the results obtained by the examples and their interpretation.
Perceptions of injectable opioid agonist treatment (iOAT) among people who regularly use opioids in Australia: findings from a cross‐sectional study in three Australian cities
Authors: Nielsen Suzanne , Sanfilippo Paul , Belackova Vendula , Day Carolyn , Silins Ed , Lintzeris Nicholas , Bruno Raimondo , Grebely Jason , Lancaster Kari , Ali Robert , Bell James , Dietze Paul , Degenhardt Louisa , Farrell Michael , Larance Briony
Published: October 2020

Background and aims

Not all people experiencing opioid dependence benefit from oral opioid agonist treatment. The aim of this study was to examine perceptions of (supervised) injectable opioid agonist treatment (iOAT) (described as ‘an opioid similar to heroin self‐injected at a clinic several times a day’) among people who regularly use opioids and determine how common iOAT eligibility criteria accord with interest in iOAT.

Design

Cross‐sectional survey

Setting

Sydney, Melbourne and Hobart, Australia

Participants

A total of 344 people (63% male) who use opioids regularly and had ever injected opioids, interviewed December 2017–March 2018. The mean age of participants was 41.5 years [standard deviation (SD) = 8.5].

Measurements

Primary outcome measures were interest in iOAT, factors associated with interest and the proportion of participants who would be eligible using common criteria from trials and guidelines. We examined willingness to travel for iOAT, medication preferences and perspectives on whom should receive iOAT.

Findings

Overall, 53% of participants (n = 182) believed that iOAT would be a good treatment option for them. Participants who believed that iOAT was a good treatment option for them were more likely to be male [adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) = 1.10–2.82], have used heroin in the past month (aOR = 6.03, 95% CI = 2.86–12.71), currently regularly inject opioids (aOR = 1.84, 95% CI = 1.16–2.91) and have met ICD‐10 criteria for opioid dependence (aOR = 3.46, 95% CI = 1.65–7.24). Those interested in iOAT had commenced more treatment episodes (aOR =1.06, 95% CI = 1.00–1.12). Among those interested in iOAT (n = 182), 26% (n = 48) met common eligibility criteria for iOAT.

Conclusions

Interest in injectable opioid agonist treatment does not appear to be universal among people who regularly use opioids. Among study participants who expressed interest in injectable opioid agonist treatment, most did not meet common eligibility criteria.
Spatial distribution, sampling efficiency and Taylor's power law. 2. Interpreting density‐dependent sampling efficiency
Authors: Taylor R. A. J.
Published: October 2020

The intimate relationship between sampling efficiency and Taylor's power law (TPL) was investigated with gypsy moth sample data. The data were used to compute sampling efficiency directly and indirectly by TPL.

Comparison of TPLs and efficiency plots of male and female pupae confirmed the identities linking TPL with sampling efficiency. Divergence of sex‐specific TPL plots indicated local scale density‐dependent sex ratio.

Egg mass sample data confirmed the sampling efficiency and TPL identities provided the same variance and mean vectors were used to compute TPLs. Small differences in sample numbers destroy the identities but approximate efficiency estimates are still obtainable from the TPLs. Sampling efficiency of timed walks, fixed area and variable area surveys were estimated and ranked.

Rescaling moth catches per trap to number per unit volume changes slope, intercept and correlation coefficient while stretching the pattern of data points. Comparison of absolute density estimates over two different time intervals showed density‐dependent variation declining with increasing sample interval.

Fitting power laws by ordinary dependent regression is less efficient than fitting by geometric mean regression and produces biased regression parameters. The significance of this for the analysis and interpretation of ecological sample data generally is discussed.
What Motivates Reasoning? A Theory of Goal‐Dependent Political Evaluation
Authors: Groenendyk Eric , Krupnikov Yanna
Published: October 2020

Rather than exhibiting bias or open‐minded reasoning at baseline, we argue that information processing is motivated by whatever goals a context makes salient. Thus, if politics feels like debate, people will be motivated to argue for their side. If politics feels like deliberation, they will be motivated to seek consensus through open‐minded processing. Results from three experiments demonstrate: (1) Politics evokes thoughts similar to conflictual contexts and dissimilar from deliberative contexts. (2) Consequently, information labeled “political” primes the motivation to counterargue, leading to opinion polarization. Absent such labeling, no such motivation is evident, explaining why bias is common but not inherent to politics. (3) Despite this capacity for bias, people can be motivated to actively process and accept counterattitudinal information by simply making the value of open‐mindedness salient. This suggests open‐minded discourse is possible even absent motivation to evaluate information accurately. We conclude by discussing the implications of our research for political discourse.
Stockpiling in the time of COVID‐19
Authors: Micalizzi Lauren , Zambrotta Nicholas S. , Bernstein Michael H.
Published: October 2020

Objectives

Consistent with behaviour observed in prior crises, individuals are stockpiling supplies during the novel coronavirus (COVID‐19) pandemic. The goal of this study was to describe stockpiling behaviour in response to COVID‐19 and investigate individual predictors of stockpiling.

Methods

Workers (N = 363, 54.72% male, 44.65% female, 0.63% other; Mage = 38.41, SD = 12.48, range = 18‐78) were recruited from Amazon’s Mechanical Turk and completed a survey about their stockpiling of 13 items, as well as behaviours and opinions surrounding the COVID‐19 pandemic and their political affiliation.

Results

Participants stockpiled, on average, approximately 6 items, and toilet paper was the item most commonly procured. Approximately 25% of the sample acquired a gun or other weapon in response to the pandemic and approximately 20% of participants stockpiled gold or other precious metals. Stockpiling was more commonly observed among individuals who were more conservative, worried more about the pandemic, and social distanced less.

Conclusions

Individual, societal, and ideological implications are discussed.
Dysregulation of BMP9/BMPR2/SMAD signalling pathway contributes to pulmonary fibrosis and pulmonary hypertension induced by bleomycin in rats
Authors: Jiang Qian , Liu Chunli , Liu Shiyun , Lu Wenju , Li Yi , Luo Xiaoyun , Ma Ran , Zhang Chenting , Chen Haixia , Chen Yuqin , Zhang Zizhou , Hong Cheng , Guo Wenliang , Wang Tao , Yang Kai , Wang Jian
Published: October 2020

Background and Purpose

Pulmonary hypertension related to pulmonary fibrosis is classed as WHO Group III, one of the most common groups which lacks effective treatment options. In this study, we aimed to uncover the underlying mechanisms, particularly the involvement of the BMP9/BMPR2/SMAD signalling pathway, in this subtype of pulmonary hypertension.

Experimental Approach

Male Sprague Dawley rats were used to establish a model of pulmonary hypertension with pulmonary fibrosis, induced by bleomycin. Haemodynamic and lung functions were measured, along with histological and immunohistochemical examinations. Primary cultures of rat pulmonary microvascular endothelial cells (PMVECs) were analysed with western blots, apoptosis assays and immunohistochemistry.

Key Results

Early (7 days) after bleomycin treatment of rats, pulmonary arterial thickening and severe loss of pulmonary arterial endothelium were observed, followed (14 days) by increased right ventricular systolic pressure and right ventricular hypertrophy. Marked down‐regulation of the BMP9/BMPR2/SMAD signalling pathway was markedly down‐regulated in lung tissues from bleomycin‐treated rats (throughout the 7‐ to 35‐day treatment period) and bleomycin‐treated rat PMVECs, along with excessive cell apoptosis and loss of pulmonary arterial endothelium. Treatment with recombinant human bone morphogenetic protein 9 (rhBMP9) attenuated these aspects of bleomycin‐induced pulmonary hypertension, by restoring disrupted BMP9/BMPR2/SMAD signalling.

Conclusion and Implications

In bleomycin‐treated rats, early and persisting suppression of the BMP9/BMPR2/SMAD signalling pathway triggered severe loss of pulmonary arterial endothelium and subsequent pulmonary arterial vascular remodelling, contributing to the development of pulmonary hypertension. Therapeutic approaches reinforcing BMP9/BMPR2/SMAD signalling might be ideal strategies for this subtype of pulmonary hypertension.

LINKED ARTICLES

This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment
Authors: Wang Fang , Wang Xin , Li Na , Liu Juan , Zhang Lin , Hui Lingyun , Feng Ai , Wang Zhonglin , Wang Yawen
Published: October 2020

To select the most efficient chemical to induce apoptosis in leukemia cells, a multidrug screen was applied on bone marrow mononuclear cells from chronic myeloid leukemia (CML) patients. Oprozomib (Cpd 21) was chosen for the subsequent experiments. The isobaric tags for relative and absolute quantitation (iTRAQ) was then performed to identify the responsible pathway relative to apoptosis and the results showed that endoplasmic reticulum (ER) chaperones were upregulated. Apoptosis was attributed to a joint effect of calcium leakage andPERK and IRE1α phosphorylation. The PERK branch was responsible for the first wave of cell death that occurred within 24 hours. The later wave of apoptosis was mediated by IRE1α, which transmit apoptotic signals through the ASK‐JNK‐BIM axis. Release of Ca2+ from ER into cytosol resulted in activation of calpain, which, in turn, cleaved caspase‐12. Our data also explained the selective killing effects of oprozomib on CML cells, which relied on proteasome activity. The present study demonstrated that prolonged inhibition of proteasome to trigger unfolded protein response could be an alternative strategy for treating CML in light of tyrosine kinase inhibitors resistance.
Differential glycosylation of collagen modulates lung cancer stem cell subsets through β1 integrin‐mediated interactions
Authors: Gardelli Cecilia , Russo Laura , Cipolla Laura , Moro Massimo , Andriani Francesca , Rondinone Ornella , Nicotra Francesco , Sozzi Gabriella , Bertolini Giulia , Roz Luca
Published: October 2020

In lung cancer, CD133+ cells represent the subset of cancer stem cells (CSC) able to sustain tumor growth and metastatic dissemination. CSC function is tightly regulated by specialized niches composed of both stromal cells and extracellular matrix (ECM) proteins, mainly represented by collagen. The relevance of collagen glycosylation, a fundamental post‐translational modification controlling several biological processes, in regulating tumor cell phenotype remains, however, largely unexplored. To investigate the bioactive effects of differential ECM glycosylation on lung cancer cells, we prepared collagen films functionalized with glucose (Glc‐collagen) and galactose (Gal‐collagen) exploiting a neoglycosylation approach based on a reductive amination of maltose and lactose with the amino residues of collagen lysines. We demonstrate that culturing of tumor cells on collagen determines a glycosylation‐dependent positive selection of CSC and triggers their expansion/generation. The functional relevance of CD133+ CSC increase was validated in vivo, proving an augmented tumorigenic and metastatic potential. High expression of integrin β1 in its active form is associated with an increased proficiency of tumor cells to sense signaling from glycosylated matrices (glyco‐collagen) and to acquire stemness features. Accordingly, inhibition of integrin β1 in tumor cells prevents CSC enrichment, suggesting that binding of integrin β1 to Glc‐collagen subtends CSC expansion/generation. We provide evidence suggesting that collagen glycosylation could play an essential role in modulating the creation of a niche favorable for the generation and selection/survival of lung CSC. Interfering with this crosstalk may represent an innovative therapeutic strategy for lung cancer treatment.
Kinetic studies of galectin-10 release from eosinophils exposed to proliferating T cells
Authors: Lingblom C , Andersson K , Wennerås C
Published: October 2020

Galectin-10 is involved in the T cell suppressive activity of regulatory T cells and eosinophils alike. We have identified a subpopulation of T cell suppressive eosinophils that express CD16 on the surface and contain more galectin-10 compared with conventional CD16-negative eosinophils. Our main goal was to determine how the intracellular protein galectin-10 is released from eosinophils when exposed to proliferating T cells and if such release could be inhibited. Confocal microscopy and imaging flow cytometry were used to study the release of galectin-10 from eosinophils incubated with polyclonally activated T cells. T cell proliferation was monitored by measurement of the incorporation of [3H]-thymidine. Initially, galectin-10-containing synapses formed between eosinophils and T cells. Subsequently, the plasma membrane of eosinophils began to disintegrate and cap-like accumulations of galectin-10 budded on the eosinophil cell surface. Lastly, eosinophil extracellular traps composed of nuclear DNA and galectin-10 were freed. It was solely the CD16-expressing suppressive eosinophils that formed synapses and eosinophil extracellular traps containing galectin-10. Dissolution of the extracellular traps by DNase I partly abrogated the T cell suppression exerted by eosinophils. Extracellular trap formation has mainly been associated with anti-bacterial defense, but we show a new putative function of these cellular formations, as mediators of T cell suppression by enabling the release of galectin-10 from eosinophils.
Longitudinal economic analysis of Bonebridge 601 versus percutaneous bone‐anchored hearing devices over a 5‐year follow‐up period
Authors: Amin Nikul , Soulby Andrew Jonathan , Borsetto Daniele , Pai Irumee
Published: October 2020

Objectives

Percutaneous bone‐anchored hearing devices (pBAHDs) are the most commonly used bone conduction implants (BCI). Concerns surround the long‐term complications, notably skin‐related, in patients with percutaneous abutments. The active transcutaneous BCI Bonebridge system can help avoid some of these pitfalls but is often considered a second‐line option due to various factors including perceived increased overall costs.

Design

Longitudinal economic analysis of Bonebridge BCI 601 versus pBAHD over a 5‐year follow‐up period.

Setting

A specialist hearing implant centre.

Participants

Adult patients (≥16 years) with conductive hearing loss, mixed hearing loss or single‐sided deafness, who received a Bonebridge or pBAHD implant between 1/7/2013 and 1/12/2018 with a minimum 12‐month follow‐up.

Main outcome measures

We compared the mean costs per implanted patient for both implants at 1, 3 and 5 years postoperative time points. Clinical effectiveness was evaluated using objective and patient‐reported outcome measures.

Results

The mean total cost per patient of Bonebridge was significantly higher than pBAHD at 1‐year post‐implantation (£8512 standard deviation [SD] £715 vs £5590 SD £1394, P < .001); however, by 5‐years post‐implantation this difference was no longer statistically significant (£12 453 SD £2159 vs £12 575 SD £3854, P > .05). The overall cost convergence was mainly accounted for by the increased long‐term complications, revision surgery rates and higher cost of the pBAHD external processor compared to Bonebridge.

Conclusions

Long‐term costs of Bonebridge to healthcare providers are comparable to pBAHDs, whilst offering lower complication rates, comparable audiological benefit and patient satisfaction. Bonebridge should be considered as a first‐line BCI option in appropriate cases.
ZNF300 promotes chemoresistance and aggressive behaviour in non‐small‐cell lung cancer
Authors: Yu Shilong , Ao Zhi , Wu Yi , Song Liyuan , Zhang Peng , Li Xiaokang , Liu Min , Qian Pin , Zhang Ruijie , Li Xihua , Chen Yan , Wang Xuanbin , Wang Xianhui , Ruan Xuzhi , Qian Guisheng , Ji Fuyun
Published: October 2020

Objectives

Chemoresistance induced by cisplatin has become the major impediment to lung cancer chemotherapy. This study explored the potential chemoresistant genes and underlying mechanisms of chemoresistance in NSCLC.

Materials and methods

Gene expression profile was integrated with DNA methylation profile to screen the candidate chemoresistant genes. Bioinformatic analysis and immunohistochemistry were used to analyse the association of a candidate gene with the characteristics of NSCLC patients. Recombinant lentivirus vectors were utilized to overexpress or silence candidate gene. Microarrays and immunoblotting were applied to explore the downstream targets of candidate gene. Xenograft models were established to validate the findings in vitro.

Results

An increased ZNF300 expression was detected in three chemoresistant cell lines of NSCLC, and the higher expression of ZNF300 was associated with poor OS of NSCLC patients. Cells with upregulated ZNF300 presented chemoresistance and enhanced aggressive growth compared to cells with downregulated ZNF300. ZNF300 inhibited MAPK/ERK pathways and activated CDK1 through inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. ICA and ATRA improved the anti‐tumour effect of cisplatin on chemoresistant cells by inducing differentiation.

Conclusions

ZNF300 promotes chemoresistance and aggressive behaviour of NSCLC through regulation of proliferation and differentiation by downregulating MAPK/ERK pathways and regulation of slow‐cycling phenotype via activating CDK1 by inhibiting WEE1/MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. Cisplatin, combined with ATRA and ICA, might be beneficial in chemoresistant cases of NSCLC.
Intravascular ultrasound–guided selection for early noninvasive cardiac allograft vasculopathy screening in heart transplant recipients
Authors: Nelson Lærke Marie , Rossing Kasper , Ihlemann Nikolaj , Boesgaard Søren , Engstrøm Thomas , Gustafsson Finn
Published: October 2020

Background

Noninvasive screening for cardiac allograft vasculopathy (CAV) instead of invasive coronary angiography (ICA) within the first 3 to 5 years after heart transplantation (HTx) is controversial. We evaluated a strategy of intravascular ultrasound (IVUS)–guided conversion to early noninvasive screening post‐HTx.

Methods

A single‐center study of 103 consecutive HTx recipients from 2008 to 2018 undergoing ICA at 1 year post‐HTx. Of 88 patients with normal 1‐year ICA, sixty‐six patients underwent IVUS examination for risk stratification by maximal intimal thickness (MIT) into (i) low‐risk group (MIT < 0.5 mm) (n = 41, 62%) followed noninvasively versus (ii) high‐risk group (MIT ≥ 0.5 mm) (n = 25, 38%) followed with yearly ICA. Both groups underwent ICA at year 5 post‐HTx. We evaluated a combined endpoint of angiographic CAV and death at 5‐year follow‐up post‐HTx.

Results

Median (IQR) age was 51 (33–60) years, and 62% were male. Follow‐up was 1443 (1125–1456) days. Survival free from angiographic CAV (Kaplan‐Meier) differed significantly between groups (log‐rank p < .0001). A subgroup of 27 patients completed ICA at year 5, and the proportion of angiographic CAV was significantly lower in low‐risk patients (p < .0001).

Conclusion

IVUS‐guided selection for early noninvasive CAV screening appears to be safe and holds promise as a novel strategy for early risk stratification and CAV surveillance post‐HTx.
Use as directed: do standard drink labels on alcohol containers help consumers drink (ir)responsibly? Real‐world evidence from a quasi‐experimental study in Yukon, Canada
Authors: Schoueri‐Mychasiw Nour , Weerasinghe Ashini , Stockwell Tim , Vallance Kate , Hammond David , Greenfield Thomas K. , McGavock Jonathan , Hobin Erin
Published: October 2020

Introduction and Aims

This paper examines the impact of an alcohol labelling intervention on recall of and support for standard drink (SD) labels, estimating the number of SDs in alcohol containers, and intended and unintended use of SD labels.

Design and Methods

A quasi‐experimental study was conducted in Canada where labels with a cancer warning, national drinking guidelines and SD information were applied to alcohol containers in the single liquor store in the intervention site, while usual labelling continued in the two liquor stores in the comparison site. Three waves of surveys were conducted in both sites before and at two time‐points after the intervention with 2049 cohort participants. Generalised estimating equations were applied to estimate changes in all outcomes.

Results

Participants in the intervention relative to the comparison site had greater odds of recalling [adjusted odds ratio (AOR) 5.69, 95% confidence interval (CI) 3.02, 10.71] and supporting SD labels (AOR 1.49, 95% CI 1.04, 2.12) and lower odds of reporting using SD labels to purchase high strength, low‐cost alcohol (AOR 0.65, 95% CI 0.45, 0.93). Exposure to the labels had negligible effects on accurately estimating the number of SDs (AOR 1.06, 95% CI 0.59, 1.93) and using SD labels to drink within guidelines (AOR 1.04, 95% CI 0.75, 1.46).

Discussion and Conclusions

Evidence‐informed labels increased support for and decreased unintended use of SD labels. Such labels can improve accuracy in estimating the number of SDs in alcohol containers and adherence to drinking guidelines.
Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem
Authors: Northrop Amanda C. , Avalone Vanessa , Ellison Aaron M. , Ballif Bryan A. , Gotelli Nicholas J.
Published: October 2020

Incremental increases in a driver variable, such as nutrients or detritus, can trigger abrupt shifts in aquatic ecosystems that may exhibit hysteretic dynamics and a slow return to the initial state. A model system for understanding these dynamics is the microbial assemblage that inhabits the cup‐shaped leaves of the pitcher plant Sarracenia purpurea. With enrichment of organic matter, this system flips within three days from an oxygen‐rich state to an oxygen‐poor state. In a replicated greenhouse experiment, we enriched pitcher‐plant leaves at different rates with bovine serum albumin (BSA), a molecular substitute for detritus. Changes in dissolved oxygen (DO) and undigested BSA concentration were monitored during enrichment and recovery phases. With increasing enrichment rates, the dynamics ranged from clockwise hysteresis (low), to environmental tracking (medium), to novel counter‐clockwise hysteresis (high). These experiments demonstrate that detrital enrichment rate can modulate a diversity of hysteretic responses within a single aquatic ecosystem, and suggest different management strategies may be needed to mitigate the effects of high vs. low rates of detrital enrichment.
Early transcriptional changes after UVB treatment in atopic dermatitis include inverse regulation of IL‐36γ and IL‐37
Authors: Lossius Astrid H. , Berents Teresa L. , Sætre Frank , Nilsen Hogne R , Bradley Maria , Asad Samina , Haraldsen Guttorm , Sundnes Olav , Holm Jan‐Øivind
Published: October 2020

Phototherapy with narrow‐band Ultraviolet B (nb‐UVB) is a major therapeutic option in atopic dermatitis (AD), yet knowledge of the early molecular responses to this treatment is lacking. The objective of this study was to map the early transcriptional changes in AD skin in response to nb‐UVB treatment. Adult patients (n = 16) with AD were included in the study and scored with validated scoring tools. AD skin was irradiated with local nb‐UVB on day 0, 2 and 4. Skin biopsies were taken before and after treatment (day 0 and 7) and analysed for genome‐wide modulation of transcription. When examining the early response after three local UVB treatments, gene expression analysis revealed 77 significantly modulated transcripts (30 down‐ and 47 upregulated). Among them were transcripts related to the inflammatory response, melanin synthesis, keratinization and epidermal structure. Interestingly, the pro‐inflammatory cytokine IL‐36γ was reduced after treatment, while the anti‐inflammatory cytokine IL‐37 increased after treatment with nb‐UVB. There was also a modulation of several other mediators involved in inflammation, among them defensins and S100 proteins. This is the first study of early transcriptomic changes in AD skin in response to nb‐UVB. We reveal robust modulation of a small group of inflammatory and anti‐inflammatory targets, including the IL‐1 family members IL36γ and IL‐37, which is evident before any detectable changes in skin morphology or immune cell infiltrates. These findings provide important clues to the molecular mechanisms behind the treatment response and shed light on new potential treatment targets.
Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms
Authors: Büttner‐Herold Maike , Sticht Carsten , Wiech Thorsten , Porubsky Stefan
Published: October 2020

Aims

Renal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs.

Methods and results

The cohort comprised 29 patients (23 men) aged 67 ± 11 years (mean ± standard deviation), diagnosed with chronic myeloid leukaemia (n = 5), polycythaemia vera (n = 9), primary myelofibrosis (n = 5), essential thrombocythaemia (n = 2), or chronic myelomonocytic leukaemia (n = 4), as well as MPNs or MDS/MPNs not otherwise specified (n = 4). Patients manifested with proteinuria (93%), partially in the nephrotic range (46%), haematuria (72%), and impaired kidney function (93%). The most prominent histological findings included double‐contoured glomerular basement membranes (71%), acute endothelial damage (68%), intracapillary platelet aggregation (62%), mesangiolysis (21%), thrombotic microangiopathy (24%), segmental glomerulosclerosis (66%), mesangial hypercellularity and sclerosis, extramedullary haematopoiesis (17%), and also IgA nephropathy (21%) and glomerulonephritis (GN) with features of infection‐related GN (21%). MPN and MDS/MPN patients showed significantly more chronic changes than age‐matched and sex‐matched controls, including global and segmental glomerulosclerosis, mesangial sclerosis, and hypercellularity, whereas the extent of arteriosclerosis was comparable.

Conclusions

MPN and MDS/MPN patients show glomerular scarring that exceeds age‐related phenomena. Ongoing endothelial damage, growth factors released by platelets and deposition of immune complexes are probably the causative mechanisms. Early recognition of renal failure heralded by proteinuria and haematuria, and consequent control of risk factors for kidney failure, should be recommended for MPN and MDS/MPN patients.
MicroRNAs in urine as diagnostic biomarkers for multiple myeloma
Authors: Li Jia , Wang Chengbin , Meng Qian , Hu Zhiying , Hu Mei , Zhang Man
Published: October 2020

Introduction

Multiple myeloma (MM) is a hematological malignancy. It is of great clinical significance to screen microRNAs (miRNAs) in urine as noninvasive diagnostic biomarkers for MM.

Methods

Urinary miRNAs in MM were performed by Agilent Bioanalyzer 2100 and verified by quantitative real‐time PCR (qRT‐PCR). Receiver operator characteristic (ROC) was used to evaluate the diagnostic value of abnormal miRNAs for MM. Progression‐free survival (PFS) of MM was calculated by Kaplan‐Meier.

Results

In microarray analysis, twelve down‐regulated miRNAs dysregulated in MM. The expression levels of miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y were validated. These miRNAs were significantly lower in MM (P < .05), but there was no significant difference between newly diagnosed, relapse, and remission group of MM (P> .05). ROC curve analysis showed that the sensitivity of miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y to MM was 91.7%, 100%, 100%, and 91.7%, and the specificity was 66.7%, 75.0%, 75.0%, and 100%, respectively. The four miRNAs were negatively correlated with the total urinary light chain (r = −0.427 P = .030, r = −0.461 P = .018, r = −0.469 P = .016, r = −0.493 P = .011). In addition, miR‐134‐5p, miR‐6500‐5p, and miR‐548q were positively correlated with serum ALB (r = 0.518 P = .006, r = 0.400 P = .039,r = 0.492 P = .009). The expression level of miRNAs had no significant influence on PFS in MM patients (P> .05).

Conclusion

The results show that miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y are potential noninvasive diagnostic biomarkers for MM.
Effectiveness of healthy eating interventions among children: A quantitative systematic review
Authors: Shorey Shefaly , Chan Valerie
Published: October 2020

Aims

This review aimed to evaluate the effectiveness of healthy eating interventions among normal‐weight children.

Design

A systematic review of randomized controlled trials.

Data sources

Seven databases were searched from the inception of each database until September 2019.

Review Methods

A systematic review of quantitative studies was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and the PRISMA extension for reporting a synthesis without a meta‐analysis.

Results

Fifteen studies were included in this review. A meta‐analysis could not be conducted because of the observed heterogeneity across studies. There were mixed effects of the included interventions on healthy eating habits, ranging from effective to not effective. Only a few studies found behavioural determinants effective in enhancing healthy eating.

Conclusion

Because of the observed heterogeneity and varied outcome variables, a meta‐analysis could not be conducted, and the overall effectiveness of the included interventions could not be verified. Interventions that were theory based, parent focused, and delivered through the multimodal interactive approach were found to be effective in enhancing healthy eating habits among children. More studies involving peers that are institution based need to be conducted.
Histamine receptor 1 is expressed in leukaemic cells and affects differentiation sensitivity
Authors: Cornet‐Masana Josep M. , Banús‐Mulet Antònia , Cuesta‐Casanovas Laia , Carbó José M. , Guijarro Francesca , Torrente Miguel Ángel , Esteve Jordi , Risueño Ruth M.
Published: October 2020

Despite the success of immunotherapy in several haematological neoplasms, the effectiveness in acute myeloid leukaemia (AML) is still controversial, partially due to the lack of knowledge regarding immune‐related processes in this disease and similar neoplasias. In this study, we analysed the role and expression of histamine receptor 1 (HRH1) in haematological malignancies. Although the histamine receptor type 1 was widely expressed in healthy and malignant haematopoiesis, especially along the myeloid lineage, HRH1 lacked a relevant role in survival/proliferation and chemoresistance of AML cells, as analysed by HRH1 knockdown (KD) and pharmacological modulation. However, HRH1‐mediated signalling was critical for the activation of the differentiation process induced by several agents including all‐trans retinoic acid, establishing a role for HRH1 in myeloid differentiation. Pharmacological activation of Erk was able to partially restore differentiation capacity in HRH1 KD AML cells, suggesting that HRH1 signalling acts upstream MAPK‐Erk pathway. As an indirect consequence of our results, treatment‐related histamine release is not expected to confer a proliferative advantage in leukaemic cells.
Treatment with interleukin‐33 is non‐toxic and protects retinal pigment epithelium in an ageing model of outer retinal degeneration
Authors: Clare Alison J. , Copland David A. , Nicholson Lindsay B. , Liu Jian , Neal Chris R. , Moss Stephen , Dick Andrew D. , Theodoropoulou Sofia
Published: October 2020

The leading cause of central vision loss, age‐related macular degeneration (AMD), is a degenerative disorder characterized by atrophy of retinal pigment epithelium (RPE) and photoreceptors. For 15% of cases, neovascularization occurs, leading to acute vision loss if left untreated. For the remaining patients, there are currently no treatment options and preventing progressive RPE atrophy remains the main therapeutic goal. Previously, we have shown treatment with interleukin‐33 can reduce choroidal neovascularization and attenuate tissue remodelling. Here, we investigate IL‐33 delivery in aged, high‐fat diet (HFD) fed mice on a wildtype and complement factor H heterozygous knockout background. We characterize the non‐toxic effect following intravitreal injection of IL‐33 and further demonstrate protective effects against RPE cell death with evidence of maintaining metabolic retinal homeostasis of Cfh+/−~HFD mice. Our results further support the potential utility of IL‐33 to prevent AMD progression.
The olfactory responses of mirid bugs to six plant extracts and their volatiles
Authors: Yin Haichen , Li Wenjing , Xu Min , Xu Dong , Wan Peng
Published: October 2020

Many methods for management of mirid bugs, one of the major pest species in cotton fields, have been developed in recent decades. The use of attractive plant volatiles may be a safe and effective alternative compared with chemical pesticides. Very little is known about the responses of the bugs to some specific volatiles. In this study, the attractive effects for the mirid bug Apolygus lucorum were evaluated and compared among ethanol extracts obtained from six types of plants. The results showed that A. lucorum had the highest selection response rate to the extract from Allium tuberosum seeds and 70.51% of the adults tended to choose this odour source. Among 40 identified compounds of the volatiles comprising A. tuberosum seed extracts, diethyl phthalate and methyl levulinate had significantly higher attractive effects than that of cotton leaves, but the respective selection response rates were less than 65%. We found that when methyl levulinate and diethyl phthalate were mixed in volume ratios of 3:7 and 6:4, the selection response rates of A. lucorum for the mixtures were 54.67% and 63.65%, respectively. These response rates were significantly higher than those for the two compounds presented alone. Furthermore, the selection response rates of A. lucorum based on these mixtures reached 82.75% and 75.73%, respectively when compared with cotton leaves. The two volatile mixtures also showed a significantly higher attractive effect for Adelphocoris suturalis, with respective selection response rates at 74.58% and 77.80% when compared with cotton leaves. Moreover, the two attractants showed no difference between the responses of male and female mirid bugs. We concluded that an appropriate application of the attractants described herein has the potential to develop a safe and effective approach for the monitoring and control of mirid bugs in cotton fields.
Cytochrome oxidase gene sequencing reveals channel catfish ovary cell line is contaminated with brown bullhead cells
Authors: Ford Lorelei , Subramaniam Kuttichantran , Waltzek Thomas B. , Bowser Paul R. , Hanson Larry
Published: October 2020

The channel catfish (Ictalurus punctatus, Rafinesque) ovary (CCO) cell line is the standard cell line used for channel catfish diagnostics. Next‐gen sequencing studies of a virus cultured in the CCO cells revealed mitochondrial sequences matching those of brown bullhead (Ameiurus nebulosus, Lesueur). Therefore, we systematically performed partial cytochrome oxidase 1 gene sequencing of several sources of the CCO cell line and all matched the brown bullhead and not the channel catfish.
Prevention of post‐endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non‐steroidal anti‐inflammatory drugs: A systematic review and network meta‐analysis
Authors: Oh Hyoung‐Chul , Kang Hyun , Park Tae Young , Choi Geun Joo , Lehman Glen A
Published: October 2020

Background and Aims

Rectally administered non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post‐endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta‐analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP.

Methods

We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents.

Results

The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high‐risk group.

Conclusions

Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.
COMMENTSBridging the Gap: Commentary on “The High Prevalence of Skin Diseases in Adults Aged 70 and Older”
Authors: Sreekantaswamy Shreya A. , Shahin Tala B. , Butler Daniel C.
Published: October 2020

See the Reply by Sinikumpu et al.
An investigation of recommended serve food portions and attaining energy and protein requirements in older adults living in residential care
Authors: Sossen L. , Bonham M. , Porter J.
Published: October 2020

Background

Ageing populations show a propensity for reduced food intake, which impacts nutritional adequacy. Nutrition guidelines for residential care homes (RCHs) are currently based on serve size of core food groups and do not consider nutrient density. The present study aimed to investigate the weight of foods served/consumed compared to recommended serve sizes and to compare energy and protein intake with individual requirements.

Methods

This was an observational study of older adults living in four RCHs. Dietary intake was estimated through the difference between weighed reference meals and a single, double‐weighed 24‐h food plate waste collected from each participant. FoodWorks9® (Xyris® Software, Brisbane, Australia) was used to calculate energy, protein and serves of core food groups from food intake and the menu provided to recommended serve sizes. Individual intake was compared with nutrition guidelines and estimated energy and protein requirements.

Results

Across 420 participants, 9.8% completed a main meal (lunch or dinner). The servings provided [248 g; interquartile range (IQR) = 206–290 g] were less than the recommended servings for a main meal (306 g = protein/starch/two vegetables), with 157 g (IQR = 109–221 g) consumed. The menu provided for minimum serves of all core food groups except for dairy. Median energy intake (n = 389) (5272 kJ day−1, IQR = 4229–6720 kJ) and protein intake (47.3 g day−1, IQR = 35.9–60.8 g) were less than estimated requirements (8181 kJ day−1, IQR = 7300–9338 kJ day−1; 76.7 g day−1, IQR = 66.7–90.8 g).

Conclusions

Nutritional needs were not met in this cohort. The findings of the present study highlight the need for smaller, nutrient‐dense meals and revised menu standards to ensure nutritional adequacy in this vulnerable population.
Characteristics of aquaporin 1, 3, and 5 expression during early murine salivary gland development
Authors: de Paula Fernanda , Tucker Abigail S. , Teshima Tathyane Harumi N. , de Souza Milena Monteiro , Coutinho‐Camillo Cláudia Malheiros , Nico Marcello Menta S. , Lourenço Silvia Vanessa
Published: October 2020

Aquaporins (AQPs) are essential to coordinate the transit of water and ions through the cell membrane. In salivary glands (SGs), AQPs have been associated with saliva formation, facilitating water absorption through the epithelium during the formation of hypotonic saliva, which is then secreted into the oral cavity. Different members of the AQP family have been suggested to play distinct roles during embryonic development, highlighted by their specific expression patterns. Here, we have investigated the expression patterns of AQP‐1, AQP‐3 and AQP‐5 by immunofluorescence at key stages of salivary gland development, utilising cultured mouse embryonic submandibular (SMG) and sublingual (SLG) glands. The expression of AQPs was compared to a mitotic marker, phospho‐histone 3 (PH3), a myoepithelial marker, smooth muscle actin (SMA), and a vascular marker, CD31. Qualitative analysis revealed that AQP‐1 and AQP‐3 were primarily expressed during the earlier phases of SG morphogenesis and were associated with cells undergoing mitotic processes (PH3‐positive). AQP‐5, in contrast, was not associated to mitotic figures, but was predominantly expressed during late stages of SG morphogenesis. Our results highlight that AQPs are expressed from early stages of SG morphogenesis and exhibit complimentary expression patterns that may contribute to the morphogenesis of salivary glands.
Drive‐through transcutaneous bilirubin screening for neonatal jaundice: A safe and efficient system during the COVID‐19 pandemic
Authors: Chua Bee‐Sim , Song Li‐Herng , Chang Chee‐Tao , Lim Xin‐Jie , Nachiappan Jeyaseelan
Published: October 2020

The coronavirus disease 2019 (COVID‐19) cases was on an increasing trend, including in Malaysia. The Malaysian Ministry of Health had implemented a range of measures, such as the use of masks and social distancing, to reduce the risk of transmission. Traditionally, newborns are evaluated for neonatal jaundice using visual assessment, a capillary heel prick and serum bilirubin (SB) sampling in primary health‐care clinics. This approach requires the physical presence of both parents and their newborns in the primary health‐care clinics, causing crowding and increasing the risk of COVID‐19 infections. To alleviate crowding, we implemented the transcutaneous bilirubin drive‐through (DT) service, which is an established, non‐invasive, painless and rapid method to determine the bilirubin levels. Throughout the screening, both parents and baby will be confined to their car. A total of 1842 babies were screened in our DT setting from April to July 2020. Of the total babies, 298 (16.1%) required venesection for SB measurement and 85 required admission for phototherapy. None with severe jaundice were missed since the implementation of this service. The average test duration per neonate was less than 5 min, while conventional venous bilirubin laboratory testing required an average of 1.5 h per neonate. The cost of the SB laboratory test and consumables was approximately USD 5 per test, with an estimated cost savings of USD 7720. DT screening may be introduced in health‐care settings to reduce crowding and eliminate the need of painful blood sampling in newborns.