bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple retinal astrocytic hamartomas in siblings with lebers congenital amaurosis: a case series and review of literature
Authors: Paul Lagan , Kumar Sumit , Singh Shalini , Jain Tanya
Published: September 2020

Background

Leber’s congenital amaurosis (LCA) is a known inherited retinal disease (IRD) associated with severe visual loss, nystagmus, amaurotic pupils, oculo-digital sign and markedly reduced or absent electroretinograms (ERG). Retinal astrocytic hamartomas (RAH) is a benign vascularized glial tumor of the retina. There is no known association of these two entities, more so in siblings.

Case presentation

A pair of siblings diagnosed as LCA who presented with RAH with no extraocular symptoms or signs of phakomatosis were imaged. Multimodal imaging was performed and are elaborately described in this article.

Conclusion

LCA in siblings with multiple RAHs is an extremely rare association. Recent advances in retinal imaging tools have aided in diagnosing even subtle and early RAH with high sensitivity using Infrared imaging (IRI) and Optical coherence tomography (OCT).
Serial multiple mediation of the association between internet gaming disorder and suicidal ideation by insomnia and depression in adolescents in Shanghai, China
Authors: Yu Yuelin , Yang Xue , Wang Suping , Wang Huwen , Chang Ruijie , Tsamlag Lhakpa , Zhang Shuxian , Xu Chen , Yu Xiaoyue , Cai Yong , Lau Joseph T. F.
Published: September 2020

Background

High prevalence and strong relationships among suicidal ideation, Internet gaming disorder (IGD), insomnia, and depression have been reported for adolescents worldwide, but the mechanism underlying these psychological problems remains unclear. This cross-sectional study explored the mediating effect of insomnia and depression on the association between IGD and suicidal ideation.

Methods

Participants were 1066 adolescents (median age = 13.0 years) with Internet games exposure in the previous 12 months from junior high schools in Shanghai, China. Questionnaire measures of suicidal ideation, IGD, insomnia, depressive symptoms, and background characteristics were obtained. Path analysis was conducted to test the multiple mediating roles of insomnia and depression.

Results

Suicidal ideation, IGD, insomnia, and depression prevalence was 27.2, 13.6, 9.2, and 17.0%, respectively. A serial multiple mediation model was generated. The mediation effect of insomnia and depression on the pathway from IGD to suicidal ideation was 45.5% (direct effect: standardized estimate [Std. estimate] = 0.186; total indirect effect: Std. estimate = 0.155). The association between IGD and depression was partially mediated by insomnia (direct effect: Std. estimate = 0.211; indirect effect: Std. estimate = 0.135). The proposed model fit the data well.

Conclusions

Insomnia and depression may serially mediate the association between IGD and suicidal ideation. IGD was positively associated with insomnia, then with depression, which in turn positively contributed to suicidal ideation. We suggest greater monitoring of Internet use and prevention of insomnia and depression to mitigate the risk of suicidal ideation among Chinese adolescents.
Protocol of a randomized controlled trial to test the effects of client-centered Representative Payee Services on antiretroviral therapy adherence among marginalized people living with HIV
Authors: Olaniyan Abisola , Creasy Stephanie L. , Batey D. Scott , Brooks Maria Mori , Maulsby Catherine , Musgrove Karen , Hagan Elizabeth , Martin Deborah , Sashin Courtenay , Farmartino Christina , Hawk Mary
Published: September 2020

Background

Client-Centered Representative Payee (CCRP) is an intervention modifying implementation of a current policy of the US Social Security Administration, which appoints organizations to serve as financial payees on behalf of vulnerable individuals receiving Social Security benefits. By ensuring beneficiaries’ bills are paid while supporting their self-determination, this structural intervention may mitigate the effects of economic disadvantage to improve housing and financial stability, enabling self-efficacy for health outcomes and improved antiretroviral therapy adherence. This randomized controlled trial will test the impact of CCRP on marginalized people living with HIV (PLWH). We hypothesize that helping participants to pay their rent and other bills on time will improve housing stability and decrease financial stress.

Methods

PLWH (n = 160) receiving services at community-based organizations will be randomly assigned to the CCRP intervention or the standard of care for 12 months. Fifty additional participants will be enrolled into a non-randomized (“choice”) study allowing participant selection of the CCRP intervention or control. The primary outcome is HIV medication adherence, assessed via the CASE adherence index, viral load, and CD4 counts. Self-assessment data for ART adherence, housing instability, self-efficacy for health behaviors, financial stress, and retention in care will be collected at baseline, 3, 6, and 12 months. Viral load, CD4, and appointment adherence data will be collected at baseline, 6, 12, 18, and 24 months from medical records. Outcomes will be compared by treatment group in the randomized trial, in the non-randomized cohort, and in the combined cohort. Qualitative data will be collected from study participants, eligible non-participants, and providers to explore underlying mechanisms of adherence, subjective responses to the intervention, and implementation barriers and facilitators.

Discussion

The aim of this study is to determine if CCRP improves health outcomes for vulnerable PLWH. Study outcomes may provide information about supports needed to help economically fragile PLWH improve health outcomes and ultimately improve HIV health disparities. In addition, findings may help to refine service delivery including the provision of representative payee to this often-marginalized population. This protocol was prospectively registered on May 22, 2018 with ClinicalTrials.gov (NCT03561103).
Correction to: Evaluation of the impact of breastfeeding support groups in primary health centres in Andalusia, Spain: a study protocol for a cluster randomized controlled trial (GALMA project)
Authors: Rodríguez-Gallego Isabel , Leon-Larios Fatima , Ruiz-Ferron Cecilia , Lomas-Campos Maria-de-las-Mercedes
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
What do you mean by “palliative sedation”?
Authors: Kremling Alexander , Schildmann Jan
Published: September 2020

Background

Sedation in palliative care is frequently but controversially discussed. Heterogeneous definitions and conceptual confusion have been cited as contributing to different problems 1) relevant to empirical research, for example, inconsistent data about practice, the ‘data problem’, and 2) relevant for an ethically legitimate characterisation of the practice, the ‘problem of ethical pre-emption’. However, little is known about how exactly definitions differ, how they cause confusion and how this can be overcome.

Method

Pre-explicative analyses: (A) systematic literature search for guidelines on sedation in palliative care and systematic decomposition of the definitions of the practice in these guidelines; (B) logical distinction of different ways through which the two problems reported might be caused by definitions; and (C) analysis of how content of the definitions contributes to the problems reported in these different ways.

Results

29 guidelines from 14 countries were identified. Definitions differ significantly in both structure and content. We identified three ways in which definitions can cause the ‘data problem’ – 1) different definitions, 2) deviating implicit concepts, 3) disagreement about facts. We identified two ways to cause the problem of ethical pre-emption: 1) explicit or 2) implicit normativity. Decomposition of definitions linked to the distinguished ways of causing the conceptual problems shows how exactly single parts of definitions can cause the problems identified.

Conclusion

Current challenges concerning empirical research on sedation in palliative care can be remediated partly by improved definitions in the future, if content and structure of the used definitions is chosen systematically. In addition, future research should bear in mind that there are distinct purposes of definitions. Regarding the ‘data problem’, improving definitions is possible in terms of supplementary information, checking for implicit understanding, systematic choice of definitional elements. ‘Ethical pre-emption’, in contrast, is a pseudo problem if definitions and the relationship of definitions and norms of good practice are understood correctly.
Deep learning-enabled analysis reveals distinct neuronal phenotypes induced by aging and cold-shock
Authors: Saberi-Bosari Sahand , Flores Kevin B. , San-Miguel Adriana
Published: September 2020

Background

Access to quantitative information is crucial to obtain a deeper understanding of biological systems. In addition to being low-throughput, traditional image-based analysis is mostly limited to error-prone qualitative or semi-quantitative assessment of phenotypes, particularly for complex subcellular morphologies. The PVD neuron in Caenorhabditis elegans, which is responsible for harsh touch and thermosensation, undergoes structural degeneration as nematodes age characterized by the appearance of dendritic protrusions. Analysis of these neurodegenerative patterns is labor-intensive and limited to qualitative assessment.

Results

In this work, we apply deep learning to perform quantitative image-based analysis of complex neurodegeneration patterns exhibited by the PVD neuron in C. elegans. We apply a convolutional neural network algorithm (Mask R-CNN) to identify neurodegenerative subcellular protrusions that appear after cold-shock or as a result of aging. A multiparametric phenotypic profile captures the unique morphological changes induced by each perturbation. We identify that acute cold-shock-induced neurodegeneration is reversible and depends on rearing temperature and, importantly, that aging and cold-shock induce distinct neuronal beading patterns.

Conclusion

The results of this work indicate that implementing deep learning for challenging image segmentation of PVD neurodegeneration enables quantitatively tracking subtle morphological changes in an unbiased manner. This analysis revealed that distinct patterns of morphological alteration are induced by aging and cold-shock, suggesting different mechanisms at play. This approach can be used to identify the molecular components involved in orchestrating neurodegeneration and to characterize the effect of other stressors on PVD degeneration.
Association of plasma chromium with metabolic syndrome among Chinese adults: a case-control study
Authors: Chen Sijing , Zhou Li , Guo Qianqian , Fang Can , Wang Mengke , Peng Xiaobo , Yin Jiawei , Li Shuzhen , Zhu Yalun , Yang Wei , Zhang Yan , Shan Zhilei , Chen Xiaoyi , Liu Liegang
Published: September 2020

Backgroud

Chromium has been suggested playing a role in alleviating diabetes, insulin resistance and lipid anomalies, but the effect on metabolic syndrome (MetS) in humans remains controversial.

Methods

We conducted a matched case-control study in a Chinese population, involving 2141 MetS cases and 2141 healthy controls, which were 1:1 matched by age (±2 years) and sex. Plasma chromium was measured by inductively coupled plasma mass spectrometry.

Results

Plasma chromium levels were lower in MetS group than in control group (mean: 4.36 μg/L and 4.66 μg/L, respectively, P < 0.001), and progressively decreased with the number of MetS components (P for trend < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence intervals) for MetS across increasing quartiles of plasma chromium levels were 1 (reference), 0.84 (0.67–1.05), 0.76 (0.61–0.95), and 0.62 (0.49–0.78), respectively (P for trend < 0.001). For the components of MetS (high waist circumference, high triglycerides and high blood glucose), the odds ratios (95% confidence intervals) of the highest quartiles were 0.77 (0.61–0.95), 0.67 (0.55–0.80), and 0.53 (0.44–0.64), respectively (P for trend < 0.05).

Conclusions

Our results indicated that plasma chromium levels were inversely associated with MetS in Chinese adults. The association may be explained by the relations between plasma chromium levels and high waist circumference, and the triglycerides and blood glucose levels.
miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators
Authors: Vergani Elisabetta , Dugo Matteo , Cossa Mara , Frigerio Simona , Di Guardo Lorenza , Gallino Gianfrancesco , Mattavelli Ilaria , Vergani Barbara , Lalli Luca , Tamborini Elena , Valeri Barbara , Gargiuli Chiara , Shahaj Eriomina , Ferrarini Marina , Ferrero Elisabetta , Gomez Lira Macarena , Huber Veronica , Del Vecchio Michele , Sensi Marialuisa , Leone Biagio Eugenio , Santinami Mario , Rivoltini Licia , Rodolfo Monica , Vallacchi Viviana
Published: September 2020

Background

Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance.

Methods

The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy.

Results

miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor.

Conclusions

Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment.

Graphical Abstract
HIV and the tuberculosis “set point”: how HIV impairs alveolar macrophage responses to tuberculosis and sets the stage for progressive disease
Authors: Auld Sara C. , Staitieh Bashar S.
Published: September 2020

As HIV has fueled a global resurgence of tuberculosis over the last several decades, there is a growing awareness that HIV-mediated impairments in both innate and adaptive immunity contribute to the heightened risk of tuberculosis in people with HIV. Since early immune responses to Mycobacterium tuberculosis (Mtb) set the stage for subsequent control or progression to active tuberculosis disease, early host–pathogen interactions following Mtb infection can be thought of as establishing a mycobacterial “set point,” which we define as the mycobacterial burden at the point of adaptive immune activation. This early immune response is impaired in the context of HIV coinfection, allowing for a higher mycobacterial set point and greater likelihood of progression to active disease with greater bacterial burden. Alveolar macrophages, as the first cells to encounter Mtb in the lungs, play a critical role in containing Mtb growth and establishing the mycobacterial set point. However, a number of key macrophage functions, ranging from pathogen recognition and uptake to phagocytosis and microbial killing, are blunted in HIV coinfection. To date, research evaluating the effects of HIV on the alveolar macrophage response to Mtb has been relatively limited, particularly with regard to the critical early events that help to dictate the mycobacterial set point. A greater understanding of alveolar macrophage functions impacted by HIV coinfection will improve our understanding of protective immunity to Mtb and may reveal novel pathways amenable to intervention to improve both early immune control of Mtb and clinical outcomes for the millions of people worldwide infected with HIV.
Using volunteered geographic information to assess mobility in the early phases of the COVID-19 pandemic: a cross-city time series analysis of 41 cities in 22 countries from March 2nd to 26th 2020
Authors: Vannoni Matia , McKee Martin , Semenza Jan C. , Bonell Chris , Stuckler David
Published: September 2020

Objectives

Restricting mobility is a central aim for lowering contact rates and preventing COVID-19 transmission. Yet the impact on mobility of different non-pharmaceutical countermeasures in the earlier stages of the pandemic is not well-understood.

Design

Trends were evaluated using Citymapper’s mobility index covering 2nd to 26th March 2020, expressed as percentages of typical usage periods from 0% as the lowest and 100% as normal. China and India were not covered. Multivariate fixed effects models were used to estimate the association of policies restricting movement on mobility before and after their introduction. Policy restrictions were assessed using the Oxford COVID-19 Government Response Stringency Index as well as measures coding the timing and degree of school and workplace closures, transport restrictions, and cancellation of mass gatherings.

Setting

41 cities worldwide.

Main outcome measures

Citymapper’s mobility index.

Results

Mobility declined in all major cities throughout March. Larger declines were seen in European than Asian cities. The COVID-19 Government Response Stringency Index was strongly associated with declines in mobility (r = − 0.75, p < 0.001). After adjusting for time-trends, we observed that implementing non-pharmaceutical countermeasures was associated with a decline of mobility of 10.0% for school closures (95% CI: 4.36 to 15.7%), 15.0% for workplace closures (95% CI: 10.2 to 19.8%), 7.09% for cancelling public events (95% CI: 1.98 to 12.2%), 18.0% for closing public transport (95% CI: 6.74 to 29.2%), 13.3% for restricting internal movements (95% CI: 8.85 to 17.8%) and 5.30% for international travel controls (95% CI: 1.69 to 8.90). In contrast, as expected, there was no association between population mobility changes and fiscal or monetary measures or emergency healthcare investment.

Conclusions

Understanding the effect of public policy on mobility in the early stages is crucial to slowing and reducing COVID-19 transmission. By using Citymapper’s mobility index, this work provides the first evidence about trends in mobility and the impacts of different policy interventions, suggesting that closure of public transport, workplaces and schools are particularly impactful.
Evaluation of three-dimensional acromiohumeral distance in the standing position and comparison with its conventional measuring methods
Authors: Yoshida Yuki , Matsumura Noboru , Yamada Yoshitake , Yamada Minoru , Yokoyama Yoichi , Matsumoto Morio , Nakamura Masaya , Nagura Takeo , Jinzaki Masahiro
Published: September 2020

Background

Narrowing of the acromiohumeral distance (AHD) implies a rotator cuff tear. However, conventional AHD measurements using two-dimensional (2D) imaging or with the patient in the supine position might differ from that while standing during daily activity. This study aimed to evaluate the three-dimensional (3D) actual distance between the acromion and humeral head in the standing position and compare the AHD values with those obtained using conventional measuring methods.

Methods

Computed tomography (CT) images of 166 shoulders from 83 healthy volunteers (31 male and 52 female; mean age 40.1 ± 5.8 years; age range, 30–49 years) were prospectively acquired in the supine and standing positions using conventional and upright CT scanners, respectively. The minimum distance between the acromion and humeral head on the 3D surface models was considered as the 3D AHD. We measured the 2D AHD on anteroposterior digitally reconstructed radiographs. The AHD values were compared between the supine and standing positions and between the 2D and 3D measurements.

Results

The mean values of 2D AHD were 8.8 ± 1.3 mm (range, 5.9–15.4 mm) in the standing position and 8.1 ± 1.2 mm (range, 5.3–14.3 mm) in the supine position. The mean values of 3D AHD were 7.3 ± 1.4 mm (range, 4.7–14.0 mm) in the standing position and 6.6 ± 1.2 mm (range, 4.4–13.7 mm) in the supine position. The values of 3D AHD were significantly lower than those of 2D AHDs in both the standing and supine positions (P < 0.001). The values of 2D and 3D AHDs were significantly lower in the supine position than in the standing position (P < 0.001).

Conclusions

This study evaluated the 3D AHD of normal shoulders in the standing position using an upright CT scanner. The present results indicated that assessments in the supine position can underestimate the value of the AHD compared with those made in the standing position and that assessments using 2D analysis can overestimate the value.
Medical costs of Alpha-1 antitrypsin deficiency-associated COPD in the United States
Authors: Sieluk Jan , Slejko Julia F. , Silverman Henry , Perfetto Eleanor , Mullins C. Daniel
Published: September 2020

Background

There are limited data on economic aspects of the genetic variant of chronic obstructive pulmonary disease (COPD) in the context of the more prevalent form of COPD. The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among COPD patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis.

Methods

Retrospective analysis of OptumLabs® Data Warehouse claims (OLDW; 2000–2017). The OLDW is a comprehensive, longitudinal real-world data asset with de-identified lives across claims and clinical information. AATD-associated COPD cases were matched with up to 10 unique non-AATD-associated COPD controls. Healthcare resource use and costs were assigned into the following categories: office (OV), outpatient (OP), and emergency room visits (ER), inpatients stays (IP), prescription drugs (RX), and other services (OTH). A generalized linear model was used to estimate total pre- and post-index (initial COPD diagnosis) costs from a third-party payer’s perspective (2018 USD) controlling for confounders. Healthcare resource utilization was estimated using a negative binomial regression.

Results

The study population consisted of 8881 patients (953 cases matched with 7928 controls). The AATD-associated COPD cohort had higher expenditures and use of office visits (OV) and other (OTH) services, as well as OV, outpatient (OP), emergency room (ER), and prescription drugs (RX) before and after the index date, respectively. Adjusted total all-healthcare cost ratios for AATD-associated COPD patients as compared to controls were 2.04 [95% CI: 1.60–2.59] and 1.98 [95% CI: 1.55–2.52] while the incremental cost difference totaled $6861 [95% CI: $3025 - $10,698] and $5772 [95% CI: $1940 - $9604] per patient before and after the index date, respectively.

Conclusions

Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar COPD patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.
Clinical management of lung cancer patients during the outbreak of COVID-19 epidemic
Authors: Wang Li , Jiang Man , Qu Jialin , Zhou Na , Zhang Xiaochun
Published: September 2020

The rapid growth of 2019 novel coronavirus (COVID-19) outbreak in Wuhan, China, at the early December 2019. COVID-19 spread all over the word just a few months. The outbreak of COVID-19 infection poses major threat to international health and economy. World Health Organization (WHO) announced that the new coronavirus was an international public health emergency on January 30, 2020. However, with the spread of COVID-19, the routine medical care of lung cancer patients was affected. Because lung cancer patients have low immunity after anti-tumor treatment, they should become the main targets for epidemic prevention. Lung cancer patients are increasingly concerned about the prevention of COVID-19. It is necessary to provide individualized medical treatment and management for lung cancer patients based on patients’ conditions and regional epidemic patterns.
Prediction of mortality in critically-ill elderly trauma patients: a single centre retrospective observational study and comparison of the performance of trauma scores
Authors: Egglestone Rebecca , Sparkes David , Dushianthan Ahilanandan
Published: September 2020

Background

Trauma in the elderly (≥ 65 years) population is increasing. This study compares the performance of trauma scoring systems in predicting 30-day mortality among the traumatised elderly patients admitted to the intensive care unit in a major trauma centre.

Methods

We collected retrospective data for all elderly trauma patients admitted to our intensive care units between January 2012 and December 2017. We assessed Injury Severity Score (ISS), Geriatric Trauma Outcome Score (GTOS) and the Trauma Audit and Research Network’s (TARN) Probability of Survival (Ps17) between survivors and non-survivors. Receiver operator characteristic (ROC) curves were used to assess the performance of these scoring systems.

Results

There were 255 elderly trauma patients with overall 30-day survival of 76%. There was a statistically significant difference in ISS, GTOS and Ps17 scores between survivors and non-survivors (p < 0.001). The area under the ROC curve (AUROC) was statistically significant for all 3, with AUROC of 0.66 (95% CI 0.59–0.74) for the ISS, 0.68 (95% CI 0.61–0.76) for the GTOS and 0.79 (95% CI 0.72–0.85) for the Ps17. The optimal cut-off points were ≥ 28, ≥ 142, ≤ 76.73 for ISS, GTOS and Ps17, respectively.

Conclusion

Both ISS and GTOS scoring systems preformed equally in predicting 30-day mortality in traumatised elderly patients admitted to the intensive care unit, however neither were robust enough to utilise in clinical practise. The Ps17 performed more robustly, although was not developed for prognosticating on individual patients. Larger prospective studies are needed to validate these scoring systems in critically-ill elderly traumatised patients, which may help to facilitate early prognostication.
Feasibility cluster randomised controlled trial evaluating a theory-driven group-based complex intervention versus usual physiotherapy to support self-management of osteoarthritis and low back pain (SOLAS)
Authors: Hurley Deirdre A. , Jeffares Isabelle , Hall Amanda M. , Keogh Alison , Toomey Elaine , McArdle Danielle , McDonough Suzanne M. , Guerin Suzanne , Segurado Ricardo , Matthews James
Published: September 2020

Background

The self-management of osteoarthritis (OA) and low back pain (LBP) through activity and skills (SOLAS) theory-driven group-based complex intervention was developed primarily for the evaluation of its acceptability to patients and physiotherapists and the feasibility of trial procedures, to inform the potential for a definitive trial.

Methods

This assessor-blinded multicentre two-arm parallel cluster randomised controlled feasibility trial compared the SOLAS intervention to usual individual physiotherapy (UP; pragmatic control group). Patients with OA of the hip, knee, lumbar spine and/or chronic LBP were recruited in primary care physiotherapy clinics (i.e. clusters) in Dublin, Ireland, between September 2014 and November 2015. The primary feasibility objectives were evaluated using quantitative methods and individual telephone interviews with purposive samples of participants and physiotherapists. A range of secondary outcomes were collected at baseline, 6 weeks (behaviour change only), 2 months and 6 months to explore the preliminary effects of the intervention. Analysis was by intention-to-treat according to participants’ cluster allocation and involved descriptive analysis of the quantitative data and inductive thematic analysis of the qualitative interviews. A linear mixed model was used to contrast change over time in participant secondary outcomes between treatment arms, while adjusting for study waves and clusters.

Results

Fourteen clusters were recruited (7 per trial arm), each cluster participated in two waves of recruitment, with the average cluster size below the target of six participants (intervention: mean (SD) = 4.92 (1.31), range 2–7; UP: mean (SD) = 5.08 (2.43), range 1–9). One hundred twenty participants (83.3% of n = 144 expected) were recruited (intervention n = 59; UP n = 61), with follow-up data obtained from 80.8% (n = 97) at 6 weeks, 84.2% (n = 101) at 2 months and 71.7% (n = 86) at 6 months. Most participants received treatment as allocated (intervention n = 49; UP n = 54). The qualitative interviews (12 participants; 10 physiotherapists (PTs) found the intervention and trial procedures acceptable and appropriate, with minimal feasible adaptations required. Linear mixed methods showed improvements in most secondary outcomes at 2 and 6 months with small between-group effects.

Conclusions

While the SOLAS intervention and trial procedures were acceptable to participants and PTs, the recruitment of enough participants is the biggest obstacle to a definitive trial.

Trial registration

ISRCTN ISRCTN49875385. Registered on 26 March 2014.
Integrating statistical and mechanistic approaches with biotic and environmental variables improves model predictions of the impact of climate and land-use changes on future mosquito-vector abundance, diversity and distributions in Australia
Authors: Madzokere Eugene T. , Hallgren Willow , Sahin Oz , Webster Julie A. , Webb Cameron E. , Mackey Brendan , Herrero Lara J.
Published: September 2020

Changes to Australia’s climate and land-use patterns could result in expanded spatial and temporal distributions of endemic mosquito vectors including Aedes and Culex species that transmit medically important arboviruses. Climate and land-use changes greatly influence the suitability of habitats for mosquitoes and their behaviors such as mating, feeding and oviposition. Changes in these behaviors in turn determine future species-specific mosquito diversity, distribution and abundance. In this review, we discuss climate and land-use change factors that influence shifts in mosquito distribution ranges. We also discuss the predictive and epidemiological merits of incorporating these factors into a novel integrated statistical (SSDM) and mechanistic species distribution modelling (MSDM) framework. One potentially significant merit of integrated modelling is an improvement in the future surveillance and control of medically relevant endemic mosquito vectors such as Aedes vigilax and Culex annulirostris, implicated in the transmission of many arboviruses such as Ross River virus and Barmah Forest virus, and exotic mosquito vectors such as Aedes aegypti and Aedes albopictus. We conducted a focused literature search to explore the merits of integrating SSDMs and MSDMs with biotic and environmental variables to better predict the future range of endemic mosquito vectors. We show that an integrated framework utilising both SSDMs and MSDMs can improve future mosquito-vector species distribution projections in Australia. We recommend consideration of climate and environmental change projections in the process of developing land-use plans as this directly impacts mosquito-vector distribution and larvae abundance. We also urge laboratory, field-based researchers and modellers to combine these modelling approaches. Having many different variations of integrated (SDM) modelling frameworks could help to enhance the management of endemic mosquitoes in Australia. Enhanced mosquito management measures could in turn lead to lower arbovirus spread and disease notification rates.
Influence of platelet storage time on human platelet lysates and platelet lysate-expanded mesenchymal stromal cells for bone tissue engineering
Authors: Shanbhag Siddharth , Mohamed-Ahmed Samih , Lunde Turid Helen Felli , Suliman Salwa , Bolstad Anne Isine , Hervig Tor , Mustafa Kamal
Published: September 2020

Background

Human platelet lysate (HPL) is emerging as the preferred xeno-free supplement for the expansion of mesenchymal stromal cells (MSCs) for bone tissue engineering (BTE) applications. Due to a growing demand, the need for standardization and scaling-up of HPL has been highlighted. However, the optimal storage time of the source material, i.e., outdated platelet concentrates (PCs), remains to be determined. The present study aimed to determine the optimal storage time of PCs in terms of the cytokine content and biological efficacy of HPL.

Methods

Donor-matched bone marrow (BMSCs) and adipose-derived MSCs (ASCs) expanded in HPL or fetal bovine serum (FBS) were characterized based on in vitro proliferation, immunophenotype, and multi-lineage differentiation. Osteogenic differentiation was assessed at early (gene expression), intermediate [alkaline phosphatase (ALP) activity], and terminal stages (mineralization). Using a multiplex immunoassay, the cytokine contents of HPLs produced from PCs stored for 1–9 months were screened and a preliminary threshold of 4 months was identified. Next, HPLs were produced from PCs stored for controlled durations of 0, 1, 2, 3, and 4 months, and their efficacy was compared in terms of cytokine content and BMSCs’ proliferation and osteogenic differentiation.

Results

BMSCs and ASCs in both HPL and FBS demonstrated a characteristic immunophenotype and multi-lineage differentiation; osteogenic differentiation of BMSCs and ASCs was significantly enhanced in HPL vs. FBS. Multiplex network analysis of HPL revealed several interacting growth factors, chemokines, and inflammatory cytokines. Notably, stem cell growth factor (SCGF) was detected in high concentrations. A majority of cytokines were elevated in HPLs produced from PCs stored for ≤ 4 months vs. > 4 months. However, no further differences in PC storage times between 0 and 4 months were identified in terms of HPLs’ cytokine content or their effects on the proliferation, ALP activity, and mineralization of BMSCs from multiple donors.

Conclusions

MSCs expanded in HPL demonstrate enhanced osteogenic differentiation, albeit with considerable donor variation. HPLs produced from outdated PCs stored for up to 4 months efficiently supported the proliferation and osteogenic differentiation of MSCs. These findings may facilitate the standardization and scaling-up of HPL from outdated PCs for BTE applications.
Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury
Authors: Ren Yifei , Chen Ying , Zheng Xizi , Wang Hui , Kang Xin , Tang Jiawei , Qu Lei , Shao Xiaoyan , Wang Suxia , Li Shuangling , Liu Gang , Yang Li
Published: September 2020

Background

Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell–cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms.

Methods

The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling.

Results

We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury.

Conclusions

We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI.
Embryonic stem cell microenvironment enhances proliferation of human retinal pigment epithelium cells by activating the PI3K signaling pathway
Authors: Liu Jiahui , Yang Liu , Wang Xiaoran , Wang Shoubi , Huang Zheqian , Li Chaoyang , Liu Ying , Cheng Yaqi , Liu Chengxiu , Wang Zhichong
Published: September 2020

Background

Retinal pigment epithelium (RPE) replacement has been proposed as an efficacious treatment for age-related macular degeneration (AMD), which is the primary cause of vision loss in the elderly worldwide. The embryonic stem cell (ESC) microenvironment has been demonstrated to enable mature cells to gain a powerful proliferative ability and even enhance the stem/progenitor phenotype via activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As the PI3K signaling pathway plays a pivotal role in proliferation and homeostasis of RPE, we hypothesize that the stemness and proliferative capability of RPE can be enhanced by the ESC microenvironment via activation of the PI3K signaling pathway.

Methods

To investigate whether the ESC microenvironment improves the stem cell phenotype and proliferation properties of human RPE (hRPE) cells by regulating the PI3K signaling pathway, primary hRPE cells were cocultured with either ESCs or human corneal epithelial cells (CECs) for 72 h, after which their proliferation, apoptosis, cell cycle progression, and colony formation were assayed to evaluate changes in their biological characteristics. Gene expression was detected by real-time PCR and protein levels were determined by western blotting or immunofluorescence. LY294002, an antagonist of the PI3K signaling pathway, was used to further confirm the mechanism involved.

Results

In comparison to hRPE cells cultured alone, hRPE cells cocultured with ESCs had an increased proliferative capacity, reduced apoptotic rate, and higher colony-forming efficiency. The expression of the stem cell-associated marker KLF4 and the differentiation marker CRALBP increased and decreased, respectively, in hRPE cells isolated from the ESC coculture. Furthermore, PI3K pathway-related genes were significantly upregulated in hRPE cells after exposure to ESCs. LY294002 reversed the pro-proliferative effect of ESCs on hRPE cells. In contrast, CECs did not share the ability of ESCs to influence the biological behavior and gene expression of hRPE cells.

Conclusions

Our findings indicate that the ESC microenvironment enhances stemness and proliferation of hRPE cells, partially via activation of the PI3K signaling pathway. This study may have a significant impact and clinical implication on cell therapy in regenerative medicine, specifically for age-related macular degeneration.
Peripheral blood-derived monocytes show neuronal properties and integration in immune-deficient rd1 mouse model upon phenotypic differentiation and induction with retinal growth factors
Authors: Mishra Alaknanda , Mohan K. Varsha , Nagarajan Perumal , Iyer Srikanth , Kesarwani Ashwani , Nath Madhu , Moksha Laxmi , Bhattacharjee Jashdeep , Das Barun , Jain Kshama , Sahu Parul , Sinha Prakriti , Velapandian T. , Upadhyay Pramod
Published: September 2020

Background

Cell therapy is one of the most promising therapeutic interventions for retinitis pigmentosa. In the current study, we aimed to assess if peripheral blood-derived monocytes which are highly abundant and accessible could be utilized as a potential candidate for phenotypic differentiation into neuron-like cells.

Methods

The peripheral blood-derived monocytes were reconditioned phenotypically using extrinsic growth factors to induce pluripotency and proliferation. The reconditioned monocytes (RM) were further incubated with a cocktail of growth factors involved in retinal development and growth to induce retinal neuron-like properties. These cells, termed as retinal neuron-like cells (RNLCs) were characterized for their morphological, molecular and functional behaviour in vitro and in vivo.

Results

The monocytes de-differentiated in vitro and acquired pluripotency with the expression of prominent stem cell markers. Treatment of RM with retinal growth factors led to an upregulation of neuronal and retinal lineage markers and downregulation of myeloid markers. These cells show morphological alterations resembling retinal neuron-like cells and expressed photoreceptor (PR) markers. The induced RNLCs also exhibited relative membrane potential change upon light exposure suggesting that they have gained some neuronal characteristics. Further studies showed that RNLCs could also integrate in an immune-deficient retinitis pigmentosa mouse model NOD.SCID-rd1 upon sub-retinal transplantation. The RNLCs engrafted in the inner nuclear layer (INL) and ganglion cell layer (GCL) of the RP afflicted retina. Mice transplanted with RNLCs showed improvement in depth perception, exploratory behaviour and the optokinetic response.

Conclusions

Thisproof-of-conceptstudy demonstrates that reconditioned monocytes can be induced to acquire retinal neuron-like properties through differentiation using a defined growth media and can be a potential candidate for cell therapy-based interventions and disease modelling for ocular diseases.
Optical solitons of space-time fractional Fokas–Lenells equation with two versatile integration architectures
Authors: Raza N. , Osman M. S. , Abdel-Aty Abdel-Haleem , Abdel-Khalek Sayed , Besbes Hatem R.
Published: September 2020

Nonlinear Schrödinger’s equation and its variation structures assume a significant job in soliton dynamics. The soliton solutions of space-time fractional Fokas–Lenells equation with a relatively new definition of local M-derivative have been recovered by utilizing improved $\tan (\frac{\phi (\eta )}{2})$
tan
(

ϕ
(
η
)

2

)
-expansion method and generalized projective Riccati equation method. The obtained solutions are periodic, dark, bright, singular, rational, along with few forms of combo-soliton solutions. These solutions are given under constraints conditions which ensure their existence. The impact of local fractional parameter is featured by its graphical portrayal. 2D and 3D diagrams are drawn to illustrate the efficacy of the conformable fractional order on the behavior of some of those solutions. The secured solutions of this model have dynamic and significant justifications for some real-world physical occurrences. Our study shows that the suggested schemes are effective, reliable, and simple for solving different types of nonlinear differential equations.
A weight-based conditional privacy-preserving authentication scheme in software-defined vehicular network
Authors: Zhong Hong , Geng Yingxue , Cui Jie , Xu Yan , Liu Lu
Published: September 2020

The rapid development of vehicular ad hoc networks (VANETs) has brought significant improvement to traffic safety and efficiency. However, owing to limitations associated with VANETs’ own unchanging model and traditional network structure, there are still many challenging concerns such as poor flexibility and controllability to deal with. To solve these inherent problems effectively, we propose a weight-based conditional anonymous authentication scheme by introducing the newly emerging software-defined networking (SDN) framework. Firstly, by making use of the global planning and dynamic management features of SDN, vehicles are classified into different priorities using weighted values to reduce communications redundancy, and control the participation of malicious vehicles. Then, an efficient conditional privacy-preserving scheme was developed to secure communications among vehicles. A two-step tracing approach has been designed to exclude and punish vehicles whose weights drop below the threshold. Extensive analyses indicate that our conditional privacy-preserving scheme is secure and has lower computation costs than conventional state-of-the-art authentication schemes.
Diabetes and eating disorders: an exploration of ‘Diabulimia’
Authors: Coleman Sophie Elizabeth , Caswell Noreen
Published: September 2020

Background

‘Diabulimia’ is the term given to the deliberate administration of insufficient insulin for the purpose of weight loss. Although Diabulimia can be life-threatening and prevalence rates in diabetes are high, there is a lack of research for how to effectively support people with the condition. This exploratory study aimed to provide much-needed information to healthcare professionals and guide the focus for future research.

Methods

Forty-five individuals with Type 1 diabetes mellitus (T1DM) and a history of insulin misuse completed an online questionnaire. This included an assessment of their eating disorder psychopathology with the Eating Disorder Examination Questionnaire (EDE-Q) and 16 open-ended questions exploring their experience of Diabulimia. The responses to the open-ended questions were analysed using thematic analysis.

Results

The average global EDE-Q score was 3.96 (1.21), which is consistent with eating disorder populations. Common themes identified were concerns about weight, difficulty coping with diabetes, past trauma, and the importance of relationships. Experiences with health professionals were overwhelmingly negative. Most participants had experienced serious medical intervention due to Diabulimia and were fully aware of the consequences of insulin restriction.

Conclusions

Overall, individuals believed that a greater awareness of Diabulimia and more training for healthcare professionals is needed. While education on insulin misuse may be a necessary first step in treatment, psychological support is crucial. To deliver effective treatment, clinicians should be aware of the specific issues facing those with Diabulimia. The current study identified themes that clinicians may find useful to consider.