bluuebunny/crossref_metadata_2025 huggingface dataset:
Periscope Proteins are variable length regulators of bacterial cell surface interactions
Authors: Whelan Fiona , Lafita Aleix , Gilburt James , Dégut Clément , Griffiths Samuel C. , Jenkins Huw T. , St John Alexander N. , Paci Emanuele , Moir James W.B. , Plevin Michael J. , Baumann Christoph G. , Bateman Alex , Potts Jennifer R.
Published: December 2020

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly-available long-read genome sequencing data, we propose this new class could contain over 50 distinct proteins, including those implicated in host colonisation and biofilm formation by human pathogens. In large multi-domain proteins, sequence divergence between adjacent domains appears to reduce inter-domain misfolding. Periscope Proteins break this “rule”, suggesting their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria and the immune system.
Mechanical frustration of phase separation in the cell nucleus by chromatin
Authors: Zhang Yaojun , Lee Daniel S.W. , Meir Yigal , Brangwynne Clifford P. , Wingreen Ned S.
Published: December 2020

Liquid-liquid phase separation is a fundamental mechanism underlying subcellular organization. Motivated by the striking observation that optogenetically-generated droplets in the nucleus display suppressed coarsening dynamics, we study the impact of chromatin mechanics on droplet phase separation. We combine theory and simulation to show that crosslinked chromatin can mechanically suppress droplets’ coalescence and ripening, as well as quantitatively control their number, size, and placement. Our results highlight the role of the subcellular mechanical environment on condensate regulation.
DeepImmuno: Deep learning-empowered prediction and generation of immunogenic peptides for T cell immunity
Authors: Li Guangyuan , Iyer Balaji , Prasath V. B. Surya , Ni Yizhao , Salomonis Nathan
Published: December 2020

T-cells play an essential role in the adaptive immune system by seeking out, binding and destroying foreign antigens presented on the cell surface of diseased cells. An improved understanding of T-cell immunity will greatly aid in the development of new cancer immunotherapies and vaccines for life threatening pathogens. Central to the design of such targeted therapies are computational methods to predict non-native epitopes to elicit a T cell response, however, we currently lack accurate immunogenicity inference methods. Another challenge is the ability to accurately simulate immunogenic peptides for specific human leukocyte antigen (HLA) alleles, for both synthetic biological applications and to augment real training datasets. Here, we proposed a beta-binomial distribution approach to derive epitope immunogenic potential from sequence alone. We conducted systematic benchmarking of five traditional machine learning (ElasticNet, KNN, SVM, Random Forest, AdaBoost) and three deep learning models (CNN, ResNet, GNN) using three independent prior validated immunogenic peptide collections (dengue virus, cancer neoantigen and SARS-Cov-2). We chose the CNN model as the best prediction model based on its adaptivity for small and large datasets, and performance relative to existing methods. In addition to outperforming two highly used immunogenicity prediction algorithms, DeepHLApan and IEDB, DeepImmuno-CNN further correctly predicts which residues are most important for T cell antigen recognition. Our independent generative adversarial network (GAN) approach, DeepImmuno-GAN, was further able to accurately simulate immunogenic peptides with physiochemical properties and immunogenicity predictions similar to that of real antigens. We provide DeepImmuno-CNN as source code and an easy-to-use web interface.

Data Availability

DeepImmuno Python3 code is available at https://github.com/frankligy/DeepImmuno. The DeepImmuno web portal is available from https://deepimmuno.herokuapp.com. The data in this article is available in GitHub and supplementary materials.
Cells protect chromosome-microtubule attachments, independent of biorientation, using an Astrin-PP1 and CyclinB-CDK1 feedback loop
Authors: Conti Duccio , Song Xinhong , Shrestha Roshan L. , Braun Dominique , Draviam Viji M
Published: December 2020

Defects in chromosome-microtubule attachment can cause chromosomal instability, associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Kinetochore pairs are bioriented and pulled by microtubules from opposing spindle poles to ensure the equal segregation of chromosomes. Kinetochore-microtubule attachments lacking opposing-pull are detached by Aurora-B/Ipl1; yet, how mono-oriented attachments that are a prerequisite for biorientation, but lacking opposing-pull are spared is unclear. Using an RNAi-mediated screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide the first evidence for how a microtubule-end associated protein senses outer-kinetochore changes specific to end-on attachments and assembles into an outer kinetochore crescent to stabilise mature attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 activities counteract each other to preserve mono-oriented attachments. Thus, cells are not only surveying chromosome-microtubule attachment errors, but they are also actively sensing and stabilising mature attachments independent of biorientation.
Multi-class Cancer Classification and Biomarker Identification using Deep Learning
Authors: Muazzam Fariha
Published: December 2020

Genetic data is important for analysing cellular functions whose disruption gives rise to various kinds of cancer. The intricacies of gene interaction are captured in various kinds of data for cancer detection through sequencing technology, but diagnosis, prognosis and treatment are still hard. Advent of machine learning helped researchers in supervised and unsupervised learning tasks along with gene identification but resourcefulness has not been overtly satisfactory. This research revolves around multi-class cancer classification, feature extraction and relevant gene identification through deep learning methods for 12 different types of cancers using RNA-SEQ from The Cancer Genome Atlas.

It has been constrained by hardware resource availability and within them the experiments that have been performed have shown promising results. Stacked De-noising Autoencoders were used for feature extraction and biomarker identification while 1D Convolutional Neural Networks for classification. Classification was performed with extracted features and relevant genes, which gave average performance of around 94% and 95% respectively. We were able to identify generic cancer-related pathways and their associated genes through Stacked De-noising Auto-encoders generated weight matrix and features. The common pathways include WNT Signalling Pathway, Angiogenesis. Moreover, across all pathways some recurrent genes were observed, namely: PIK3C2G, PCDHB8, WNT10A and these genes were found, in literature, to be involved in multiple types of cancer.

The proposed approach shows superior performance and promise against traditional techniques used by bioinformatics community, in terms of accuracy and relevant gene identification.
Amyloid Beta Oligomers Prevents Lysosomal Targeting of miRNP to Stop Its Recycling and Target Cytokine Repression in Glial Cells
Authors: De Dipayan , Bhattacharyya Suvendra N.
Published: December 2020

mRNAs encoding inflammatory cytokines are targeted by miRNAs and remain repressed in neuroglial cells. On exposure to amyloid beta 1-42 oligomers, glial cells start expressing proinflammatory cytokines although there has been increase in repressive miRNAs levels as well. Exploring the mechanism of this potential immunity of target cytokine mRNAs against repressive miRNAs in amyloid beta exposed glial cells, we have identified differential compartmentalization of repressive miRNAs in glial cells to explain this aberrant miRNA function. While the target mRNAs were found to be associated with polysomes attached to endoplasmic reticulum, the miRNPs found to be present predominantly with endosomes that failed to recycle to endoplasmic reticulum attached polysomes to repress mRNA targets in treated cells. Amyloid beta oligomers, by masking the Rab7 proteins on endosomal surface, affects Rab7 interaction with Rab Interacting Lysosomal Protein (RILP) on lysosomes to restrict endosomal maturation and its lysosomal targeting. This causes retarded miRNP targeting to lysosomes and recycling. Similar defects in miRNP retrieval has been observed in endosome maturation defective cells depleted for RILP or treated with Bafilomycin. RNA processing body localization of the miRNPs was also noted in treated cells that happens as a consequence of enhanced endosomal retention of miRNPs. Interestingly, depletion of P-body partly rescues the miRNA function in glial cells exposed to amyloid beta and restricts the excess cytokine expression there.

Graphical Abstract

Key Points

Amyloid beta exposure causes accumulation of inactive miR-146 miRNP to cause elevated proinflammatory cytokine production in glial cells.

Amyloid beta masks Rab7-RILP interaction to reduce endosome lysosome interaction.

Accumulated miRNPs failed to get targeted to lysosomes in amyloid exposed cells due to loss of endosome lysosome interaction

Lysosomal compartmentalization of miRNPs is required for its recycling and repression ofde novotargets

Accumulated miRNPs are stored in P-Bodies and depletion of P-Bodies rescues miRNA function in amyloid exposed glial cells.
How our homes impact our health: using a COVID-19 informed approach to examine urban apartment housing
Authors: Peters Terri , Halleran Anna
Published: December 2020

Purpose

The COVID-19 global health crisis is undeniably a global housing crisis. Our study focuses on quality of life in urban mid- and high-rise apartment housing, the fastest growing housing types in many cities around the world. This housing typology presents unique challenges relating to connection to nature, daylight and fresh air.

Design/methodology/approach

This multi-disciplinary literature review analyzes more than 100 published papers from peer-reviewed sources from environmental psychology, building science and architecture relevant to quality of life in high-rise housing, as well as more than 40 recent newspaper and magazine articles about the possible impacts of COVID-19 on housing. We identify synergies between passive design strategies and health-promoting architecture or “restorative environmental design” principles.

Findings

Post-pandemic, health-promoting apartment housing design must prioritize (1) window placement and views that support stress recovery and restoration; (2) lighting levels based on spaces that can satisfy multiple uses and users; (3) bedrooms designed for restful sleep that contribute to circadian regulation; (4) living rooms with better indoor air quality, with a focus on natural ventilation; (5) access to nature, through the purposeful design of balconies and (6) unit sizes and layouts that enable physical distancing and prevent crowding.

Originality/value

We identify new social and environmental design priorities in the form of evidence-based design principles to inform and promote healthy and restorative living environments for residents in apartment housing.
How should beef be produced? Consumer expectations and views on local beef production in South Tyrol (Italy)
Authors: Kühl Sarah , Busch Gesa , Gauly Matthias
Published: December 2020

Purpose

Local origin of meat acts as a key quality indicator for consumers. How an ideal local meat production should look like is rather unknown. The purpose of this study is to comprehensively analyse how an ideal local beef production should be constituted.

Design/methodology/approach

432 consumers from a North Italian province (South Tyrol) were questioned online about their views regarding (local) beef production. 12 attributes, from calf rearing to transport times, were presented with different options. Participants selected the most ideal options from their perspective. Further, willingness to pay for local beef and for the ideally produced local beef as well as the importance of local production for different food categories were assessed.

Findings

The results are quite heterogeneous but show that local production is especially of importance for eggs, dairy products and beef. Traceability to the farms, daily access to a paddock and access to pasture during summer, silage-free feeding, low transport times and suckler cow husbandry are aspects that are mostly selected as ideal. A price premium of 35% for locally produced beef and up to 50% for this ideal production seems reasonable for most consumers.

Research limitations/implications

The study only includes South Tyrolean consumers and thus the validity is limited to this area. Although transferability to other regions can be assumed, future studies are necessary to confirm this assumption.

Originality/value

This is the first study analysing consumers expectations towards local beef production considering several production levels.
Fun in the workplace and employee turnover: is less managed fun better?
Authors: Tews Michael J. , Jolly Phillip M. , Stafford Kathryn
Published: December 2020

Purpose

Despite previous research indicating that fun in the workplace has favorable outcomes, the effect of fun on turnover has not been definitively determined. The present study analyzed the direct effects on turnover of three dimensions of fun: fun activities, coworker socializing and manager support for fun, and the moderating influence of managed fun (e.g. whether fun is perceived as contrived).

Design/methodology/approach

Logistic regression was used to analyze the fun in the workplace-turnover relationship with a sample of 491 hourly associates from 141 stores of a US national retailer. Data on the fun were obtained through surveys that were paired with turnover data collected six months afterward from corporate records.

Findings

Fun activities were only found to be associated with a lower turnover when employees perceived fun as less managed. When employees perceived fun as more managed, fun activities had no effect on turnover. Coworker socializing was associated with a lower turnover when fun was perceived as less managed and higher turnover when fun was perceived as more managed.

Research limitations/implications

As the data were obtained from employees from one organization, further research would be valuable with additional samples to substantiate the generalizability of the results.

Practical implications

Given the challenge of turnover and the increasing prevalence of efforts to promote fun in the workplace, organizations should allow fun activities to be less managed (and thus more organic) to help reduce turnover.

Originality/value

While previous research has addressed managed/less managed fun in qualitative research, the present study represents the first investigation to examine this aspect of fun in the workplace from a quantitative perspective and to examine its relationship with employee turnover.
Determination and ranking of factors that are important in selecting an over-the-top video platform service among millennial consumers
Authors: Koul Shiva , Ambekar Suhas Suresh , Hudnurkar Manoj
Published: December 2020

Purpose

The purpose of this paper is to determine, rank and form composite relational factors that impact the millennial consumer’s mind-set when they opt for an access-based subscription of an over-the-top (OTT) platform service. In the competitive rising Indian market of OTT platforms, there is a need to understand what factors drive the subscription of a service for a company strategizing to build up on their customer base or for a company seeking to retain its customers.

Design/methodology/approach

The approach includes determining factors that impact the buying behavior of the consumer and have them ranked by the survey participants in order of their importance as a factor in considering a subscription of an OTT platform service. Questionnaire as a method is used for primary data collection in this research. Using “purposive sampling,” participants of the survey were determined based on their age group and current or historic consumption of at least one OTT platform service. The survey was conducted for the millennial viewership from Tier I and Tier II cities that have good internet connectivity over their mobile phones.

Findings

The result of this research is a ranking of factors based on their importance as perceived by the millennial consumers and then form composite factors, which have similarities in responses.

Practical implications

This research enables the consumers of the information to dwell on the factors that prove to be of comparative importance to the consumer and plan/forecast their strategies and further research studies accordingly.

Originality/value

A research along similar lines has been conducted for US-based OTT platforms. However, this research is specific for Indian consumers and platforms and holds significance because of growth in the Indian OTT market.
My supervisor supports me better than the past: integration of social and temporal comparison
Authors: Afshan Gul , Serrano-Archimi Carolina
Published: December 2020

Purpose

Drawing on the self-consistency theory and temporal comparison theory, this study hypothesize that relative perceived supervisor support may positively affect voice behaviour and negatively affect relationship conflict with a supervisor. This relationship happens through the underlying process of supervisor-based self-esteem acts as an underlying mechanism. But, such a relationship would be constrained by the value of temporal perceived supervisor support with high temporal perceived supervisor support strengthen this relationship as compared to low temporal perceived supervisor support.

Design/methodology/approach

Dyad data from 338 samples of employees nested within 50 supervisor workgroups from non-profit firms operating in three different cities in Sindh Pakistan were taken.

Findings

Data analysis showed that employees with a high perception of relative perceived supervisor support engaged in voice behaviour and restrain themselves from the relationship conflict. The supervisor-based self-esteem derived from supervisor support played the role of mediating this relationship. Moreover, temporal perceived supervisor support not only moderated the path between relative perceived supervisor support and supervisor-based self-esteem also the mediational strength of supervisor-based self-esteem in relative perceived supervisor support and voice behaviour and relationship conflict.

Practical implications

It is crucial to integrate social comparison in organizational support theory to view the supervisor–subordinate relationship beyond dyad. Managers should understand social comparison processes in which employees engage in to know how it affects various work attitudes and behaviours.

Originality/value

Given the importance of supervisor–subordinate relationships, the authors extend and build on the concept of social and temporal organizational support to supervisor support. The study is novel in studying such relationship and contribute to the supervisory support relationship literature beyond dyadic level.
Leader, “know yourself”: bringing back self-awareness, trust and feedback with a theory O perspective
Authors: Crook Ngaio , Alakavuklar Ozan Nadir , Bathurst Ralph
Published: December 2020

Purpose

This paper explores how leaders identify their roles and selves when they lead change in a dynamic organizational context.

Design/methodology/approach

Using a qualitative approach, ten ICT leaders participated in semi-structured interviews depicting their experiences of change. A thematic method of interpretative analysis was used to develop findings, supported by Theory U as a conceptual tool for leadership self-awareness.

Findings

Leaders struggle with organizational constraints and boundaries, specifically the complexities that form and limit their leadership underpinned by unrealistic expectations due to the construction of romanticized heroic leadership. While these restrictions lead to feelings of detachment of leaders from their organizations, leadership development exists in the acts of letting go of old behaviors, and welcoming emergence and experimentation by trusting more.

Research limitations/implications

This study may be limited by its small sample and the use of one framework to make sense of the leaders' experience of change. It confirms that change can challenge organizing norms and how leadership is identified.

Practical implications

Despite the feeling of detachment from their organizations, developing greater self-awareness, being open to new ideas and trusting more can bring about better organizational outcomes, which is represented with Theory O as a contribution both for theory and practice.

Originality/value

This study illustrates (1) leaders' inner work or personal experience of change, and (2) how improvement of self-awareness can contribute to the involvement of leaders to the change process. Based on self-awareness, trust and feedback relationship, this study suggests a new practical and conceptual tool called Theory O by advancing Theory U.
Carbonaceous components in particulate matter during a haze episode at a typical industrial area in the North China Plain
Authors: Niu Hongya , Liu Zhaoce , Hu Wei , Cheng Wenjing , Li Mengren , Xue Fanli , Wu Zhenxiao , Wang Jinxi , Fan Jingsen
Published: December 2020

Purpose

Severe airborne particulate pollution frequently occurs over the North China Plain (NCP) region in recent years. To better understand the characteristics of carbonaceous components in particulate matter (PM) over the NCP region.

Design/methodology/approach

PM samples were collected at a typical area affected by industrial emissions in Handan, in January 2016. The concentrations of organic carbon (OC) and elemental carbon (EC) in PM of different size ranges (i.e. PM2.5, PM10and TSP) were measured. The concentrations of secondary organic carbon (SOC) were estimated by the EC tracer method.

Findings

The results show that the concentration of OC ranged from 14.9 μg m−3to 108.4 μg m−3, and that of EC ranged from 4.0 μg m−3to 19.4μg m−3, when PM2.5changed from 58.0μg m−3to 251.1μg m−3during haze days, and the carbonaceous aerosols most distributed in PM2.5rather than large fraction. The concentrations of OC and EC PM2.5correlated better (r= 0.7) than in PM2.5−10and PM>10, implying that primary emissions were dominant sources of OC and EC in PM2.5. The mean ratios of OC/EC in PM2.5, PM2.5–10and PM>10were 4.4 ± 2.1, 3.6 ± 0.9 and 1.9 ± 0.7, respectively. Based on estimation, SOC accounted for 16.3%, 22.0% and 9.1% in PM2.5, PM2.5–10and PM>10respectively.

Originality/value

The ratio of SOC/OC (48.2%) in PM2.5was higher in Handan than those (28%–32%) in other megacities, e.g. Beijing, Tianjin and Shijiazhuang in the NCP, suggesting that the formation of SOC contributed significantly to OC. The mean mass absorption efficiencies of EC (MACEC) in PM10and TSP were 3.4 m2g−1(1.9–6.6 m2g−1) and 2.9 m2g−1(1.6–5.6 m2g−1), respectively, both of which had similar variation patterns to those of OC/EC and SOC/OC.
Angle domain common image gathers from reverse time migration by combining the Poynting vector with directional decomposition
Authors: Li Feipeng , Gao Jinghuai , Gao Zhaoqi , Li Chuang , Zhang Wei , Sun Wenbo
Published: December 2020

Angle domain common image gathers are crucial for seismic applications such as the migration velocity analysis and amplitude variation with angle analysis. Angle domain common image gathers are the gather of reflection coefficients when seismic waves incident at different angles on the same image point. The curvature of gathers can be used to update the migration velocity model. The amplitude variation of gathers characterizes different rock properties. Estimating the wavefield propagation direction is the most important step in the process of generating angle domain common image gathers. The wavefront propagation direction is perpendicular to the wavefront. Accurately estimating the wavefield propagation direction is crucial for calculating the reflection angle. Existing methods cannot provide the propagation direction with the high angular resolution when the subsurface structure is complex, meaning overlapped wave events exist. We propose a new method to overcome this problem. The proposed method separates overlapped waves with a directional filter bank after the up‐going and down‐going wavefield decomposition. Then, we apply the Poynting vector method to decomposed wavefield slices to determine the propagation directions of corresponding wavefield components. The key feature of the proposed method is that it does not require spatial local windows, and it is computationally efficient. Numerical tests demonstrate that our proposed method can accurately obtain the propagation direction of seismic waves in a wavefield including overlapped waves. The angle domain common image gathers generated using our proposed method have improved image quality with more accurate amplitudes and less noise compared with the angle domain common image gathers produced by the conventional Poynting vector method. It means our proposed method provides high‐quality prestack angle gathers for seismic attribute analysis.
Legacies of civil wars: A 14‐year study of social conflicts and well‐being outcomes in farming economies
Authors: Igreja Victor , Colaizzi Janna , Brekelmans Alana
Published: December 2020

Community processes to address fractured social relationships and well‐being remain the least examined dimensions in studies of legacies of civil wars. This article addresses these limitations by analyzing how the wartime and postwar generations have negotiated the legacies of the civil war (1976–1992) in a farming economy region in Mozambique. Based on a 14‐year (2002–2015) study of community courts in Mozambique, we analyzed the types of social conflicts and the associations with gender, age, risk factors, self‐described health impairments, and the timing of farming activities. We identifiedn = 3,456 participants and found that perennial sources of disputes were related to family formation and maintenance, defamation, accusations of perpetration of serious civil wartime violations, mistrust, debts, and domestic violence. Furthermore, conflict relations were associated with gender, age, risk factors, and health problems. This study concludes that civil wars have lasting multifaceted legacies, but generational tensions, availability of community institutions, and economic resources shape social relationships and well‐being outcomes while averting revenge cycles among civilian war survivors.
YouTube as a source of information on fibromyalgia
Authors: Ozsoy‐Unubol Tugba , Alanbay‐Yagci Ebru
Published: December 2020

Aim

The internet has gained popularity as a health information source for patients. YouTube is one of the biggest platforms used worldwide. Several studies showed that quality of the information on YouTube videos for patient information is poor. This study aimed to evaluate the content and quality of YouTube videos, as a source of patient information for fibromyalgia (FM).

Methods

In this cross‐sectional study, a YouTube search with the keyword "fibromyalgia" was performed, and the first 200 videos were listed according to relevancy. Advertisements, duplicate videos, videos in languages other than English, and videos without audio were excluded. Video features (number of "likes", "dislikes", views, length of video), and source of upload were recorded. DISCERN and Journal of the American Medical Association (JAMA) benchmark criteria were used for quality analysis. Video quality was assessed according to the source of upload and video features. The correlation analysis was performed between video features, JAMA, and DISCERN scores.

Results

A total number of 102 videos were analyzed. The most common source of upload was physicians and majority of the content (55.8%) was about symptoms and treatment. Mean DISCERN and JAMA scores were 35.7 and 2.2, respectively. These scores were highest in videos uploaded by physicians (52.7 and 2.6, respectively). There is a positive correlation between the duration of the video, DISCERN, and JAMA scores.

Conclusion

The majority of YouTube content has poor quality. Health professionals should be aware of the importance of health‐related information on YouTube and provide high‐quality accurate and up‐to‐date content.
Reducing the rate of psychiatric re‐admissions in bipolar disorder using smartphones—The RADMIS trial
Authors: Faurholt‐Jepsen Maria , Lindbjerg Tønning Morten , Fros Mads , Martiny Klaus , Tuxen Nanna , Rosenberg Nicole , Busk Jonas , Winther Ole , Thaysen‐Petersen Daniel , Aamund Kate Andreasson , Tolderlund Lizzie , Bardram Jakob Eyvind , Kessing Lars Vedel
Published: December 2020

Objectives

The MONARCA I and II trials were negative but suggested that smartphone‐based monitoring may increase quality of life and reduce perceived stress in bipolar disorder (BD). The present trial was the first to investigate the effect of smartphone‐based monitoring on the rate and duration of readmissions in BD.

Methods

This was a randomized controlled single‐blind parallel‐group trial. Patients with BD (ICD‐10) discharged from hospitalization in the Mental Health Services, Capital Region of Denmark were randomized 1:1 to daily smartphone‐based monitoring including a feedback loop (+ standard treatment) or to standard treatment for 6 months. Primary outcomes: the rate and duration of psychiatric readmissions.

Results

We included 98 patients with BD. In ITT analyses, there was no statistically significant difference in rates (hazard rate: 1.05, 95% CI: 0.54; 1.91, p = 0.88) or duration of readmission between the two groups (B: 3.67, 95% CI: −4.77; 12.11, p = 0.39). There was no difference in scores on the Hamilton Depression Rating Scale (B = −0.11, 95% CI: −2.50; 2.29, p = 0.93). The intervention group had higher scores on the Young Mania Rating Scale (B: 1.89, 95% CI: 0.0078; 3.78, p = 0.050). The intervention group reported lower levels of perceived stress (B: ‐7.18, 95% CI: −13.50; −0.86, p = 0.026) and lower levels of rumination (B: −6.09, 95% CI: −11.19; −1.00, p = 0.019).

Conclusions

Smartphone‐based monitoring did not reduce rate and duration of readmissions. There was no difference in levels of depressive symptoms. The intervention group had higher levels of manic symptoms, but lower perceived stress and rumination compared with the control group.
Cleavage plane after liquid‐bubble preparation of Descemet’s membrane
Authors: Rickmann Annekatrin , Wahl Silke , Katsen‐Globa Alisa , Schulz André , Pütz Norbert , Szurman Peter
Published: December 2020

Purpose

To investigate the ultrastructure of the cleavage plane of human cornea after liquid‐bubble‐prepared tissue for Descemet’s membrane endothelial keratoplasty (DMEK).

Methods

Experimental study with scanning electron microscopy (SEM) and block‐face SEM of 18 corneal specimens. Fresh human research donor corneoscleral discs (n = 12) were prepared with liquid‐bubble technique or examined as untreated controls (n = 3). In addition, Descemet’s membrane samples, n = 3, were obtained in DMEK surgery.

Results

The cleavage plane after liquid‐bubble Descemet’s membrane (DM) preparation was consistently located between interfacial matrix and posterior stromal collagen lamellae, providing a largely smooth surface exposing the amorphous interfacial zone without any significant amounts of adherent stromal remnants. No demarcation of a distinct pre‐DM layer could be detected.

Conclusion

The DMEK graft preparation performed by liquid‐bubble technique showed a smooth cleavage plane and could not reveal any demarcation of a distinct pre‐DM layer.
The effect of acetylsalicylic acid and pentoxifylline in guinea pigs with non‐alcoholic steatohepatitis
Authors: Ipsen David Højland , Skat‐Rørdam Josephine , Svenningsen Marianne , Andersen Mia , Latta Markus , Buelund Lene Elisabeth , Lintrup Kristine , Skaarup René , Lykkesfeldt Jens , Tveden‐Nyborg Pernille
Published: December 2020

Therapeutic options are urgently needed for non‐alcoholic fatty liver disease (NAFLD), but development is time‐consuming and costly. In contrast, drug repurposing offers the advantages of re‐applying compounds that are already approved, thereby reducing cost. Acetylsalicylic acid (ASA) and pentoxifylline (PTX) have shown promise for treatment of NAFLD, but have not yet been tested in combination. Guinea pigs were fed a high‐fat diet for 16 weeks and then continued on the diet while being treated with ASA, PTX or ASA+PTX for 8 weeks. Chow‐fed animals served as healthy controls. Guinea pigs were CT scanned before intervention start and at intervention end. Animals without steatosis (ie NAFLD) at week 16 were excluded from the data analysis. ASA and PTX alone or in combination did not improve hepatic steatosis, ballooning, inflammation or fibrosis nor did the treatments affect liver enzymes (aminotransferases and alkaline phosphatase) or circulating lipids. Liver triglyceride levels, relative liver weight and hepatic mRNA expression of monocyte chemoattractant protein 1, interleukin 8 and platelet‐derived growth factor b were nominally decreased. Thus, in the current study, treatment with ASA and PTX alone or in combination for 8 weeks did not ameliorate NASH or hepatic fibrosis in guinea pigs.
Benefits of robotic gait rehabilitation in cerebral palsy: lessons to be learned
Authors: Swinnen Eva , Lefeber Nina
Published: December 2020

This commentary is on the original article by Pool et al. on pages 328–335 of this issue.
Effects of whey protein plus vitamin D supplementation combined with progressive resistance training on glycaemic control, body composition, muscle function and cardiometabolic risk factors in middle‐aged and older overweight/obese adults with type 2 diabetes: A 24‐week randomized controlled trial
Authors: Miller Eliza G. , Nowson Caryl A. , Dunstan David W. , Kerr Deborah A. , Menzies David , Daly Robin M.
Published: December 2020

Aim

To determine the effect of whey protein plus vitamin D supplementation combined with progressive resistance training (PRT) on glycaemic control, body composition, muscle function and cardiometabolic risk factors in middle‐aged and older adults with type 2 diabetes (T2D).

Materials and Methods

In this 24‐week, randomized controlled trial, 198 overweight/obese adults (aged 50–75 years) with T2D undertook PRT (2‐3 days/week) with random allocation to whey protein (20 g each morning plus 20 g postexercise) plus vitamin D3 (2000 IU/day) (PRT + ProD, n = 98) or no supplementation (PRT, n = 100). Primary outcomes were HbA1c and homeostatic model assessment‐2 of insulin resistance (HOMA2‐IR). Secondary endpoints included fasting plasma glucose (FPG), body composition, muscle strength, physical function, blood pressure, blood lipids and inflammatory markers.

Results

At 24 weeks, supplementation did not enhance the effects of PRT on HbA1c (mean absolute change: PRT + ProD −0.10% [95% CI, −0.24%, 0.05%] vs. PRT −0.17% [95% CI, −0.32%, −0.03%], p = .322) or HOMA2‐IR (PRT + ProD −0.12 [95% CI, −0.27, 0.03] vs. PRT −0.03 [95% CI, −0.14, 0.09], p = .370). There were also no significant between‐group differences for the mean changes in the secondary outcomes, except that FPG improved in PRT versus PRT + ProD (net difference, 0.6 mmol/L [95% CI, 0.1, 1.0], P = .018), while interleukin IL‐10 (61% [95% CI 31%, 92%], P < .001), tumour necrosis factor‐α (16% [95% CI, 3%, 29%], p = .015) and 30‐s sit‐to‐stand performance (number, 1.0 [95% CI, −0.05, 1.5], p = .047) increased in PRT + ProD versus PRT.

Conclusions

In older overweight/obese adults with T2D, daily whey protein plus vitamin D supplementation did not augment the effects of PRT on measures of glycaemic control, body composition, muscle strength or cardiometabolic risk factors.
Pioglitazone and bariatric surgery are the most effective treatments for non‐alcoholic steatohepatitis: A hierarchical network meta‐analysis
Authors: Panunzi Simona , Maltese Sabina , Verrastro Ornella , Labbate Luca , De Gaetano Andrea , Pompili Maurizio , Capristo Esmeralda , Bornstein Stefan R. , Mingrone Geltrude
Published: December 2020

Aims

To compare different treatments for non‐alcoholic steatohepatitis (NASH) and to

determine an effectiveness hierarchy.

Materials and Methods

We conducted a systematic review and Bayesian network meta‐analysis including randomized controlled trials or prospective trials with at least 6 months' follow‐up and histologically proven NASH in adult participants. Monte Carlo simulations were performed, each generating 10 000 data points, and results are reported as medians and 95% credibility intervals (CrIs). A meta‐regression was conducted to find the effects of body mass index (BMI) decrement or reduction of homeostatic model assessment of insulin resistance (HOMA‐IR) index on non‐alcoholic fatty liver disease activity score (NAS) change.

Results

The review identified 48 eligible trials comprising 2356 adults (55.6% men). Data were pooled using a random‐effects model. The most effective treatments in terms of NAS reduction per semester were pioglitazone and Roux‐en‐Y gastric bypass (RYGB; −1.50 [95% CrI −2.08, −1.00] for pioglitazione and −1.00 [95% CrI −1.70, −0.32] for RYGB). Pioglitazone was also the best therapy for steatosis and lobular inflammation reduction. RYGB was the best treatment for hepatocellular ballooning reduction, whereas antioxidants appeared to be best for fibrosis improvement. For each 1% decrement in BMI, NAS was reduced by 1.3% (β = 1.28%, P = 0.01). Conversely, a 1% reduction of HOMA‐IR index reduced NAS by 0.3% (β = 0.31%, P < 0.001). Treatments that were regarded as promising, such as elafibranor, simtuzumab, selonsertib, cenicriviroc, obeticholic acid and liraglutide, did not reduce either NAS or liver fibrosis significantly.

Conclusions

Pioglitazione and RYGB are the most effective therapies for NASH. Antioxidants may be effective in reducing liver fibrosis. Weight loss and improvement of hepatic insulin resistance are promising approaches in the treatment of NASH.
Understanding resilience: Lessons from lived experiences of extreme poverty in Bangladesh
Authors: Maîtrot Mathilde , Wood Geof , Devine Joe
Published: December 2020

Motivation

A large donor‐funded programme in Bangladesh implemented multiple measures designed to graduate individuals and households out of extreme poverty. The programme was committed to lesson learning and advocacy. It monitored change through socioeconomic surveys, qualitative tracking methods, real time assessment and project evaluations. The qualitative tracking in particular shed light on the nature of extreme poverty and resilience.

Purpose

Is extreme poverty different from moderate poverty, and in what ways? Do the extreme poor experience more idiosyncratic poverty than structural or systemic poverty? Are the extreme poor more likely to be women and girls more socially isolated and marginalized due to their gender, thus impeding their capabilities? What support is needed to enable recovery and transformation from crises?

Approach and methods

Between 2011 and 2015, 72 life histories of households enrolled in a major poverty reduction programme were conducted, entailing repeated ethnographical engagement with informants. This showed how most households experience ups and downs in their poverty and vulnerability through time: an experience at variance with static understandings of hazards and responses. The limitations of resilience literature are thus critiqued to develop a new theory around time preference behaviour and discounting.

Findings

Experiences of extreme poverty are not solely a function of systemic, class‐based inequality, but of the varied and reinforcing ways they intersect with idiosyncratic conditions of household life cycles, dependency ratios, gender and age balance, morbidity, ethnic discrimination and social isolation. Four key factors stand out as influencing deep poverty: (a) ill health, with significant internal opportunity costs; (b) intergenerational reproduction; (c) high incidence of female‐managed and ‐headed households, resulting from male desertion; and (d) a lack of income diversity and security.

Policy Implications

Our findings provide fresh insights into policy responses to extreme poverty. These insights suggest a policy shift away from a narrow concern with graduation to a wider focus on resilience. Resilience as a poverty reduction outcome requires interventions that support individuals (micro level), target the intergenerational reproduction of poverty (meso level), and engage with wider power structures that exploit and neglect poor people (macro level). Policy‐makers need to engage more explicitly with the meso and macro levels in particular, recognizing how the three levels converge to reproduce conditions of extreme poverty.
A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
Authors: Keefe Richard S. E. , Woods Scott W. , Cannon Tyrone D. , Ruhrmann Stephan , Mathalon Daniel H. , McGuire Philip , Rosenbrock Holger , Daniels Kristen , Cotton Daniel , Roy Dooti , Pollentier Stephane , Sand Michael
Published: December 2020

Aim

Attenuated psychosis syndrome (APS), a condition for further study in the Diagnostic and Statistical Manual of Mental Disorders‐5, comprises psychotic symptoms that are qualitatively similar to those observed in schizophrenia but are less severe. Patients with APS are at high risk of converting to first‐episode psychosis (FEP). As evidence for effective pharmacological interventions in APS is limited, novel treatments may provide symptomatic relief and delay/prevent psychotic conversion. This trial aims to investigate the efficacy, safety, and tolerability of BI 409306, a potent and selective phosphodiesterase‐9 inhibitor, versus placebo in APS. Novel biomarkers of psychosis are being investigated.

Methods

In this Phase II, multinational, double‐blind, parallel‐group trial, randomized (1:1) patients will receive BI 409306 50 mg or placebo twice daily for 52 weeks. Patients (n = 300) will be enrolled to determine time to remission of APS, time to FEP, change in everyday functional capacity (Schizophrenia Cognition Rating Scale), and change from baseline in Brief Assessment of Cognition composite score and Positive and Negative Syndrome Scale scores. Potential biomarkers of psychosis under investigation include functional measures of brain activity and automated speech analyses. Safety is being assessed throughout.

Conclusions

This trial will determine whether BI 409306 is superior to placebo in achieving sustainable remission of APS and improvements in cognition and functional capacity. These advances may provide evidence‐based treatment options for symptomatic relief in APS. Furthermore, the study will assess the effect of BI 409306 on psychotic conversion and explore the identification of patients at risk for conversion using novel biomarkers.
Mouse models of atopic dermatitis: a critical reappraisal
Authors: Gilhar Amos , Reich Kristian , Keren Aviad , Kabashima Kenji , Steinhoff Martin , Paus Ralf
Published: December 2020

Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so‐called “AD” mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more “allergic” or “irriant” contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research. Here, we propose to initiate a rational debate on the minimal criteria that a mouse model should meet in order to be considered relevant for human AD. We suggest that valid AD models should at least meet the following criteria: (a) an AD‐like epidermal barrier defect with reduced filaggrin expression along with hyperproliferation, hyperplasia; (b) increased epidermal expression of thymic stromal lymphopoietin (TSLP), periostin and/or chemokines such as TARC (CCL17); (c) a characteristic dermal immune cell infiltrate with overexpression of some key cytokines such as IL‐4, IL‐13, IL‐31 and IL‐33; (d) distinctive “neurodermatitis” features (sensory skin hyperinnervation, defective beta‐adrenergic signalling, neurogenic skin inflammation and triggering or aggravation of AD‐like skin lesions by perceived stress); and (e) response of experimentally induced skin lesions to standard AD therapy. Finally, we delineate why humanized AD mouse models (human skin xenotransplants on SCID mice) offer a particularly promising preclinical research alternative to the currently available “AD” mouse models.
Cholesterol glucosylation–based survival strategy in Helicobacter pylori
Authors: Qaria Majjid A. , Qumar Shamsul , Sepe Ludovico P. , Ahmed Niyaz
Published: December 2020

Helicobacter pylori is a major chronic health problem, infecting more than half of the population worldwide. H. pylori infection is linked with various clinical complications ranging from gastritis to gastric cancer. The resolution of gastritis and peptic ulcer appears to be linked with the eradication of H. pylori. However, resistance to antibiotics and eradication failure rates are reaching alarmingly high levels. This calls for urgent action in finding alternate methods for H. pylori eradication. Here, we discuss the recently identified mechanism of H. pylori known as cholesterol glucosylation, mediated by the enzyme cholesterol‐α‐glucosyltransferase, encoded by the gene cgt. Cholesterol glucosylation serves several functions that include promoting immune evasion, enhancing antibiotic resistance, maintaining the native helical morphology, and supporting functions of prominent virulence factors such as CagA and VacA. Consequently, strategies aiming at inhibition of the cholesterol glucosylation process have the potential to attenuate the potency of H. pylori infection and abrogate H. pylori immune evasion capabilities. Knockout of H. pylori cgt results in unsuccessful colonization and elimination by the host immune responses. Moreover, blocking cholesterol glucosylation can reverse antibiotic susceptibility in H. pylori. In this work, we review the main roles of cholesterol glucosylation in H. pylori and evaluate whether this mechanism can be targeted for the development of alternate methods for eradication of H. pylori infection.
Requesting Trade Sanctions? The European Parliament and the Generalized Scheme of Preferences
Authors: Meissner Katharina L.
Published: December 2020

Trade policy is among the EU's major capabilities to promote fundamental rights in developing countries. Conditionality clauses thus accompany EU trade agreements and tariff preferences under the Generalised Scheme of Preferences (GSP). Yet while conditionality in trade agreements have come under the spotlight and the EP has stepped up its engagement in this area of decision‐making, the GSP has largely not been addressed in scholarly debate. This article fills this void in the literature by exploring the conditions under which the EP asks for trade sanctions on beneficiaries of the GSP. I argue that the EP invests political resources in a beneficiary when this country is salient under EU development cooperation. Hence, I observe a horizontal spill‐over effect whereby EP trade activities are driven by a country's salience in the area of development cooperation. However, this effect occurs only in the absence of security interests and the lack of development performance.