bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplicity and complexity: a qualitative exploration of influences on prescribing in UK general practice
Authors: Carter Mary , Chapman Sarah , Watson Margaret C
Published: January 2021

Objectives

Despite widespread availability of evidence-based guidelines to inform rational use of medicines, considerable unwarranted variation exists in prescribing. A greater understanding of key determinants of contemporary prescribing in UK general practice could inform strategies to promote evidence-based prescribing. This study explored (1) current influences on prescribing in general practice and (2) the possibility that general practice-based pharmacists (PBPs) may contribute to greater engagement with evidence-based prescribing.

Design

Semistructured, telephone interviews and a focus group were conducted, audio-recorded and transcribed verbatim. Thematic analysis was undertaken.

Participants

General practice prescribers: general practitioners (GPs), PBPs, nurses.

Key informants: individuals within the National Health Service (NHS) with responsibility for influencing, monitoring and measuring general practice prescribing.

Setting

General practices and NHS organisations in England.

Results

Interviews with 17 prescribers (GPs (n=6), PBPs (n=6), nurses (n=5)) and 6 key informants, and one focus group with five key informants were undertaken between November 2018 and April 2019. Determinants operating at individual, practice and societal levels impacted prescribing and guideline use. Prescribers’ professional backgrounds, for example, nursing, pharmacy, patient populations and patient pressure were perceived as substantial influences, as well as media portrayal and public perceptions of medicines.

Prescribers identified practice-level determinants of prescribing, including practice culture and shared beliefs. Key informants tended to emphasise higher-level influences, including NHS policies, availability of support and advice from secondary care and generic challenges associated with medicines use, for example, multimorbidity.

Participants expressed mixed views about the potential of PBPs to promote evidence-based prescribing in general practice.

Conclusion

Prescribing in UK general practice is influenced by multiple intersecting factors. Strategies to promote evidence-based prescribing should target modifiable influences at practice and individual levels. Customising strategies for medical and non-medical prescribers may maximise their effectiveness.
Study protocol of RESCUE-ALS: A Phase 2, randomised, double-blind, placebo-controlled study in early symptomatic amyotrophic lateral sclerosis patients to assess bioenergetic catalysis with CNM-Au8 as a mechanism to slow disease progression
Authors: Vucic Steve , Kiernan Matthew C , Menon Parvathi , Huynh William , Rynders Austin , Ho Karen S , Glanzman Robert , Hotchkin Michael T
Published: January 2021

Introduction

Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive and universally fatal neurodegenerative disorder. In Europe, Australia and Canada, riluzole is the only approved therapeutic agent for the treatment of ALS, while in the USA, riluzole and edaravone have been approved by the Food and Drug Administration (FDA) . Neither riluzole nor edaravone treatment has resulted in substantial disease-modifying effects. There is, therefore, an urgent need for drugs that result in safe and effective treatment. Here, we present the design and rationale for the phase 2 RESCUE-ALS study, investigating the novel nanocatalytic drug, CNM-Au8, as a therapeutic intervention that enhances the metabolic and energetic capacity of motor neurones. CNM-Au8 is an aqueous suspension of clean-surfaced, faceted gold nanocrystals that have extraordinary catalytic capabilities, that enhance efficiencies of key metabolic reactions, while simultaneously reducing levels of reactive oxygen species. This trial utilises a novel design by employing motor unit number index (MUNIX), measured by electromyography, as a quantitative measure of lower motor neurone loss and as an early marker of ALS disease progression.

Methods and analysis

This is a multicentre, randomised, double-blind, parallel group, placebo-controlled study of the efficacy, safety, pharmacokinetics and pharmacodynamics of CNM-Au8 in ALS patients. Patients will be randomised 1:1 to either receive 30 mg of CNM-Au8 once daily or matching placebo over a 36-week double-blind treatment period. Efficacy will be assessed as the change in motor neurone loss as measured by electromyography (eg, MUNIX, the primary endpoint; and secondary endpoints including MScanFit, motor unit size index, Split Hand Index, Neurophysiology Index). Exploratory endpoints include standard clinical and quality of life assessments.

Ethics and dissemination

RESCUE-ALS was approved by the Western Sydney Local Health District Human Research Ethics Committee (Ethics Ref: 2019/ETH12107). Results of the study will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT04098406
Low acuity paediatric emergency visits under single-payer universal health insurance in Taiwan, 2000–2015: a population-based repeated cross-sectional design
Authors: Huang I-Anne , Chou Yiing-Jenq , Chou I-Jun , Huang Yu-Tung , Huang Jhen-Ling , Jaing Tang-Her , Wu Chang-Teng , Hsiao Hsiang-Ju , Huang Nicole
Published: January 2021

Objectives

Emergency services utilisation is a critical policy concern. The paediatric population is the main user of emergency department (ED) services, and the main contributor to low acuity (LA) ED visits. We aimed to describe the trends of ED and LA ED visits under a comprehensive, universal health insurance programme in Taiwan, and to explore factors associating with potentially unnecessary ED utilisation.

Design and setting

We used a population-based, repeated cross-sectional design to analyse the full year of 2000, 2005, 2010 and 2015 National Health Insurance claims data individually for individuals aged 18 years and under.

Participants

We identified 5 538 197, 4 818 213, 4 401 677 and 3 841 174 children in 2000, 2005, 2010 and 2015, respectively.

Primary and secondary outcome measures

We adopted a diagnosis grouping system and severity classification system to define LA paediatric ED (PED) visits. Generalised estimating equation was applied to identify factors associated with LA PED visits.

Results

The annual LA PED visits per 100 paediatric population decreased from 10.32 in 2000 to 9.04 in 2015 (12.40%). Infectious ears, nose and throat, dental and mouth diseases persistently ranked as the top reasons for LA visits (55.31% in 2000 vs 33.94% in 2015). Physical trauma-related LA PED visits increased most rapidly between 2000 and 2015 (0.91–2.56 visits per 100 population). The dose–response patterns were observed between the likelihood of incurring LA PED visit and either child’s age (OR 1.06–1.35 as age groups increase, p<0.0001) or family socioeconomic status (OR 1.02–1.21 as family income levels decrease, p<0.05).

Conclusion

Despite a comprehensive coverage of emergency care and low cost-sharing obligations under a single-payer universal health insurance programme in Taiwan, no significant increase in PED utilisation for LA conditions was observed between 2000 and 2015. Taiwan’s experience may serve as an important reference for countries considering healthcare system reforms.
Systematic and continuous collection of patient-reported outcomes and experience in women with cancer undergoing mastectomy and immediate breast reconstruction: a study protocol for the Tuscany Region (Italy)
Authors: Ferrè Francesca , De Rosis Sabina , Murante Anna Maria , Gilmore Kendall Jamieson , Ghilli Matteo , Mariniello Donatella , Nuti Sabina , Roncella Manuela
Published: January 2021

Introduction

Monitoring how patients feel and what they experience during the care process gives health professionals data to improve the quality of care, and gives health systems information to better design and implement care pathways. To gain new insights about specific gaps and/or strengths in breast cancer care, we measure patient-reported outcomes (PROs) and patient-reported experiences (PREs) for women receiving immediate breast reconstruction (iBR).

Methods and analysis

Prospective, multicentre, cohort study with continuous and systematic web-based data collection from women diagnosed with breast cancer, who have an indication for iBR after mastectomy treated at any Breast Unit (BU) in Tuscany Region (Italy). Patients are classified into one of two groups under conditions of routine clinical practice, based on the type of iBR planned (implant and autologous reconstruction). Patient-reported information are obtained prior to and after surgery (at 3-month and 12-month follow-up). We estimate that there are around 700 annual eligible patients.

Descriptive analyses are used to assess trends in PROs over time and differences between types of iBR in PROs and PREs. Additionally, econometric models are used to analyse patient and BU characteristics associated with outcomes and experiences. PREs are evaluated to assess aspects of integrated care along the care pathway.

Ethics and dissemination

The study has been reviewed and obtained a nihil obstat from the Tuscan Ethics Committees of the three Area Vasta in 2017. Dissemination of results will be via periodic report, journal articles and conference presentations.
Non-pharmacological strategies for self-directed and interpersonal violence in people with severe mental illness: a rapid overview of systematic reviews
Authors: Moreno-Calvete Maria Concepcion , Ballesteros-Rodriguez Francisco Javier
Published: January 2021

Introduction

Self-directed and interpersonal violence among people with severe mental illness has become a health priority. Though non-pharmacological interventions have been investigated, to our knowledge, no summary of all systematic reviews on this topic has been reported. We will conduct a rapid overview of reviews to synthesise evidence available by identifying systematic reviews on non-pharmacological interventions for self-directed or interpersonal violence in people with severe mental illness.

Methods and analysis

This is a protocol for a rapid overview of reviews. The overview will include any systematic reviews (with or without meta-analyses) of randomised controlled trials (RCTs) or cluster RCTs that examine the effect of non-pharmacological interventions on self-directed or interpersonal violence in people with severe mental illness. This protocol applies the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Protocols, the criteria for conducting overviews of reviews in the Cochrane Handbook of Systematic Reviews of Interventions and the criteria for the Cochrane Rapid Reviews. To identify studies, a search will be performed in the following databases: PubMed, EMBASE, PsycINFO, CINAHL, LILACS, SciELO, Web of Science, Scopus, ProQuest, the Cochrane Database of Systematic Reviews through the Cochrane Library and the Epistemonikos database of systematic reviews. The searches date from inception to September 2020. The study selection process will be described using a PRISMA flow diagram, we will assess the quality of evidence in systematic reviews included and the quality of the systematic reviews themselves and the main results will be summarised in categories to provide a map of the evidence available.

Ethics and dissemination

No patients or other participants will be involved in this study. The results will be presented at mental health conferences and for publication in a peer-reviewed journal.

Registration details

The protocol was registered on the Open Science Framework (https://osf.io/myzd9/).
Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies
Authors: Pijls Bart G , Jolani Shahab , Atherley Anique , Derckx Raissa T , Dijkstra Janna I R , Franssen Gregor H L , Hendriks Stevie , Richters Anke , Venemans-Jellema Annemarie , Zalpuri Saurabh , Zeegers Maurice P
Published: January 2021

Objective

We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death.

Design

Systematic review and meta-analysis.

Data sources

PubMed and Embase through 4 May 2020.

Study selection

We considered cohort and case–control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death.

Data extraction and synthesis

We screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale.

Results

We screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years.

Conclusions

Meta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death.

PROSPERO registration number

CRD42020180085.
Over-the-counter oral contraceptive use among women in Mexico: results from a national survey
Authors: Grindlay Kate , Wollum Alexandra , Karver Jonathan , Grossman Daniel
Published: January 2021

Aim

In Mexico, many pharmacies sell oral contraceptives (OCs) over the counter (OTC); however, little is known about the background characteristics of OTC pill users. The primary objective of this study was to understand the characteristics of OTC OC users in Mexico, including whether there were differences by age, urbanicity, and insurance status. This information is instructive as other countries explore allowing OTC access to OCs.

Methods

We analysed the nationally representative 2014 Mexican National Survey of Demographic Dynamics (ENADID) among a sample of OC users aged 15–54 years (n=1970). We performed multivariable logistic models to understand the characteristics associated with OTC access, with age, urbanicity, and insurance status as our primary predictors of interest. Additionally, we descriptively explored knowledge of how frequently to take OCs by pill source and age.

Results

Some 54% of pill users, including 66% of those aged 15–17 years, obtained their OCs OTC. In multivariable regression we found no differences in OTC access by age. However, being uninsured (adjusted odds ratio (AOR) 1.86, 95% CI 1.23 to 2.82) (compared with employer-based public insurance) and living in an urban area (AOR 4.73, 95% CI 3.37 to 6.66) (compared with rural area) were associated with a higher odds of OTC access among pill users. Women’s knowledge of how frequently to take OCs was similar between OTC and prescription users within age groups.

Conclusions

These findings point to the importance of OTC availability of OCs for pill users of all ages and uninsured and urban women in Mexico in particular.
PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF
Authors: Li Jiang , Liang Xi , Jiang Jing , Yang Lingling , Xin Jiaojiao , Shi Dongyan , Lu Yingyan , Li Jun , Ren Keke , Hassan Hozeifa Mohamed , Zhang Jianing , Chen Pengcheng , Yao Heng , Li Jiaqi , Wu Tianzhou , Jin Linfeng , Ye Ping , Li Tan , Zhang Huafen , Sun Suwan , Guo Beibei , Zhou Xingping , Cai Qun , Chen Jiaxian , Xu Xiaowei , Huang Jianrong , Hao Shaorui , He Jinqiu , Xin Shaojie , Wang Di , Trebicka Jonel , Chen Xin , Li Jun
Published: January 2021

Objective

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics.

Methods

Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs).

Results

The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis.

Conclusions

This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.
Remote monitoring in heart failure: current and emerging technologies in the context of the pandemic
Authors: Mohebali Donya , Kittleson Michelle M
Published: January 2021

The incidence of heart failure (HF) remains high and patients with HF are at risk for frequent hospitalisations. Remote monitoring technologies may provide early indications of HF decompensation and potentially allow for optimisation of therapy to prevent HF hospitalisations. The need for reliable remote monitoring technology has never been greater as the COVID-19 pandemic has led to the rapid expansion of a new mode of healthcare delivery: the virtual visit. With the convergence of remote monitoring technologies and reliable method of remote healthcare delivery, an understanding of the role of both in the management of patients with HF is critical. In this review, we outline the evidence on current remote monitoring technologies in patients with HF and highlight how these advances may benefit patients in the context of the current pandemic.
Short history of 5-methylcytosine: from discovery to clinical applications
Authors: Taryma-Lesniak Olga , Sokolowska Katarzyna Ewa , Wojdacz Tomasz Kazimierz
Published: January 2021

Covalent modifications of nucleotides in genetic material have been known from the beginning of the last century. Currently, one of those modifications referred to as DNA methylation, is impacting personalised medicine both as a treatment target and a biomarker source for clinical disease management. In this short review, we describe landmark discoveries that led to the elucidation of the DNA methylation importance in the cell’s physiology and clarification of its role as one of the major processes in disease pathology. We also describe turning points in the development of methodologies to study this modification, which ultimately resulted in the development of in-vitro diagnostic kits targeting disease related DNA methylation changes as biomarkers.
Patterns of intimate partner violence against women in Europe: prevalence and associated risk factors
Authors: Podaná Zuzana
Published: January 2021

Background

Intimate partner violence (IPV) is a complex phenomenon and some research suggests that there are qualitatively distinct IPV types. However, little is known about the risk factors associated with different IPV types.

Methods

Data from Violence against women: an European Union (EU)-wide survey, conducted by the EU Agency for Fundamental Rights was used. Latent class analysis (LCA) was employed to identify distinct IPV patterns based on the intensity of eight forms of violence by current partners (n=30 675). Multilevel multinomial logistic regression was used to examine individual and country-level risk factors associated with the outcome IPV patterns.

Results

A five-class solution was selected based on the LCA results. Two classes encompassed severe coercive IPV: the intimate terrorism class (1.5%) also comprised extensive physical violence whereas the high coercive control class (2.0%) did not. The partner’s alcohol abuse, violent behaviour outside the relationship and the woman’s abuse in childhood were the main individual factors positively associated with IPV. The country’s gender equality levels were negatively associated with the odds of experiencing intimate terrorism (adjusted OR, aOR 0.35, 95% CI 0.21 to 0.56) and high coercive control (aOR 0.63, 95% CI 0.47 to 0.85) versus no IPV. Although the effects of most individual risk factors were found universally for all IPV patterns, the strongest associations were typically revealed for the intimate terrorism pattern.

Conclusion

The results support the importance of coercive control as a factor differentiating between IPV types and also highlight the need to consider IPV typologies in research. Policy implications of the findings are discussed.
‘The ethics approval took 20 months on a trial which was meant to help terminally ill cancer patients. In the end we had to send the funding back’: a survey of views on human research ethics reviews
Authors: Scott Anna Mae , Chalmers Iain , Barnett Adrian , Stephens Alexandre , Kolstoe Simon E , Clark Justin , Glasziou Paul
Published: January 2021

Background

We conducted a survey to identify what types of health/medical research could be exempt from research ethics reviews in Australia.

Methods

We surveyed Australian health/medical researchers and Human Research Ethics Committee (HREC) members. The survey asked whether respondents had previously changed or abandoned a project anticipating difficulties obtaining ethics approval, and presented eight research scenarios, asking whether these scenarios should or should not be exempt from ethics review, and to provide (optional) comments. Qualitative data were analysed thematically; quantitative data in R.

Results

We received 514 responses. Forty-three per cent of respondents to whom the question applied, reported changing projects in anticipation of obstacles from the ethics review process; 25% reported abandoning projects for this reason. Research scenarios asking professional staff to provide views in their area of expertise were most commonly exempted from ethics review (to prioritise systematic review topics 84%, on software strengths/weaknesses 85%); scenarios involving surplus samples (82%) and N-of-1 (single case) studies (76%) were most commonly required to undergo ethics review. HREC members were 26% more likely than researchers to require ethics review. Need for independent oversight, and low risk, were most frequently cited in support of decisions to require or exempt from ethics review, respectively.

Conclusions

Considerable differences exist between researchers and HREC members, about when to exempt from review the research that ultimately serves the interests of patients and the public. It is widely accepted that evaluative research should be used to reduce clinical uncertainties—the same principle should apply to ethics reviews.
Clinical and laboratory features of 244 men with primary syphilis: a 5-year single-centre retrospective study
Authors: Ramoni Stefano , Genovese Giovanni , Pastena Andrea , Casazza Giovanni , Lunghi Giovanna , Marzano Angelo Valerio , Cusini Marco
Published: January 2021

Background

Syphilis incidence has exponentially increased in recent decades, particularly among men who have sex with men (MSM). Primary syphilis is characterised by a chancre appearing at the site ofTreponema pallidum(TP) inoculation. Atypical morphological variants of syphilitic chancre are frequent. Clinical suspicion must be confirmed either by the demonstration of TP within the lesion through direct tests, such as dark field microscopy (DFM) orT. pallidumnucleic acid amplification technique (TP-NAAT), or by serological tests.

Objectives

To analyse the clinical features, the sexual behaviour and the role of diagnostic tests in a cohort of men with primary syphilis in Milan.

Methods

Epidemiological, clinical and laboratory data of male patients with primary syphilis seen at the STI Center of the University of Milan between 2015 and 2019 were retrospectively evaluated. Diagnosis was confirmed by at least one positive diagnostic test of either DFM, TP-NAAT or serology.

Results

Among a total of 244 patients, 160 (65.6%) were MSM and 32 (13.1%) were living with HIV. One hundred twenty-four (50.8%) patients had a clinically atypical chancre. Chancres were exclusively extragenital in 30 (12.3%) patients, with MSM being more commonly affected (MSM vs heterosexuals: 16.3% vs 4.8%, respectively; p=0.012), and anal region the most frequently involved site. Chancres were multiple in 68/242 (28.1%) patients and morphologically atypical in 76/244 (31.1%). Diagnosis was obtained by (1) both serology and direct methods in 158/244 patients (64.7%), (2) serology solely in 47/244 (19.3%) and (3) direct methods solely in 39/244 (16%). DFM yielded positive results in 83/139 (59.7%) patients, while TP-NAAT gave positive results in 114/121 (94.2%) patients.

Conclusions

Patients with primary syphilis frequently present with morphologically atypical chancres. Furthermore, MSM commonly exhibit extragenital involvement. A combined diagnostic approach including both direct and indirect tests is needed.
The Suzuki–Miyaura reaction of BPin-substituted F-BODIPYs with aryl halides
Authors: Smith Craig D. , Thompson Alison
Published: January 2021

F-BODIPYs substituted with BPin functionality have been coupled to aryl halides using a mild and efficient catalyst system involving Pd2(dba)3 and XPhos. The methodology enables the Suzuki–Miyaura cross-coupling of electron-rich, electron-poor, and sterically encumbered BPin-substituted F-BODIPYs to aryl halides bearing various functional groups, thus presenting an opportunity for the preparation of highly functionalised F-BODIPYs without need for the corresponding aryl moiety to be available in borylated form.
Developmental asynchrony and host species identity predict variability in nestling growth of an obligate brood parasite: a test of the “growth-tuning” hypothesis
Authors: Winnicki S.K. , Strausberger B.M. , Antonson N.D. , Burhans D.E. , Lock J. , Kilpatrick A.M. , Hauber M.E.
Published: January 2021

Generalist obligate brood parasites are excellent models for studies of developmental plasticity, as they experience a range of social and environmental variation when raised by one of their many hosts. Parasitic Brown-headed Cowbirds (Molothrus ater (Boddaert, 1783)) exhibit host-specific growth rates, yet Cowbird growth rates are not predicted by hosts’ incubation or brooding periods. We tested the novel “growth-tuning” hypothesis which predicts that total asynchrony between Cowbirds’ and hosts’ nesting periods results in faster parasitic growth in nests where host young fledge earlier than Cowbirds. We tested this prediction using previously published and newly added nestling mass data across diverse host species. Total nesting period asynchrony (summed across incubation and brooding stages) predicted Cowbird growth; 8-day-old Cowbirds were heavier in host nests with relatively shorter nesting periods. We further explored the drivers of variation in growth using mass measurements of Cowbirds in Song Sparrow (Melospiza melodia (A. Wilson, 1810)) and Red-winged Blackbird (Agelaius phoeniceus (Linnaeus, 1766)) nests. Our top models included host species (Cowbirds grew faster in Sparrow nests), numbers of nestmates (slowest when raised alone), and sex (males grew faster). These results confirm that multiple social and environmental factors predict directional patterns of developmental plasticity in avian generalist brood parasites.
An optimal MRAC–ASMC scheme for robot manipulators based on the artificial bee colony algorithm
Authors: Javad Mahmoodabadi Mohammad , Mehdi Shahangian Mohammad , Nejadkourki Nahid
Published: January 2021

In this paper, an optimal multi-adaptive robust controller is proposed for robot manipulators using the gradient descent method and artificial bee colony. At first, model reference adaptive control (MRAC) and sliding mode control (SMC) are separately designed for handling a robot manipulator with two revolute (2R) joints. Further, the coefficients of the sliding surfaces and control efforts are updated via a suitable adaptive mechanism based on the gradient descent method. In addition, to minimize the weighted summation of integral time absolute error (ITAE), some constant parameters of the controllers are determined by the artificial bee colony optimization algorithm. Finally, comparisons and performance tests are illustrated to demonstrate the effectiveness and superiority of the proposed control scheme for trajectory tracking in comparison with other traditional approaches.
Incorporating Maintenance Infeasibilities in an Aircraft Rotation Planning Model
Authors: Gopalan Ram
Published: January 2021

In any airline’s schedule development process, aircraft rotations must be planned for individual fleet types after fleet assignment. The aircraft rotation plans must conform to stringent maintenance requirements and this problem can be formulated as a periodic routing problem on an Eulerian graph. We analyze the computational complexity of developing maintenance rotations when some overnighting aircraft may not have sufficient time on the ground to complete extended maintenance (referred to as a maintenance infeasibility). The paper also provides a theoretical analysis of heuristics for the aircraft maintenance rotation problem with maintenance infeasibilities.
Facilitating Human Activity Data Annotation via Context-Aware Change Detection on Smartwatches
Authors: Akbari Ali , Martinez Jonathan , Jafari Roozbeh
Published: January 2021

Annotating activities of daily living (ADL) is vital for developing machine learning models for activity recognition. In addition, it is critical for self-reporting purposes such as in assisted living where the users are asked to log their ADLs. However, data annotation becomes extremely challenging in real-world data collection scenarios, where the users have to provide annotations and labels on their own. Methods such as self-reports that rely on users’ memory and compliance are prone to human errors and become burdensome since they increase users’ cognitive load. In this article, we propose a light yet effective context-aware change point detection algorithm that is implemented and run on a smartwatch for facilitating data annotation for high-level ADLs. The proposed system detects the moments of transition from one to another activity and prompts the users to annotate their data. We leverage freely available Bluetooth low energy (BLE) information broadcasted by various devices to detect changes in environmental context. This contextual information is combined with a motion-based change point detection algorithm, which utilizes data from wearable motion sensors, to reduce the false positives and enhance the system's accuracy. Through real-world experiments, we show that the proposed system improves the quality and quantity of labels collected from users by reducing human errors while eliminating users’ cognitive load and facilitating the data annotation process.
Multimodal multi-pedestrian path prediction for autonomous cars
Authors: Poibrenski Atanas , Klusch Matthias , Vozniak Igor , Müller Christian
Published: January 2021

Accurate prediction of the future position of pedestrians in traffic scenarios is required for safe navigation of an autonomous vehicle but remains a challenge. This concerns, in particular, the effective and efficient multimodal prediction of most likely trajectories of tracked pedestrians from egocentric view of self-driving car. In this paper, we present a novel solution, named M2P3, which combines a conditional variational autoencoder with recurrent neural network encoder-decoder architecture in order to predict a set of possible future locations of each pedestrian in a traffic scene. The M2P3 system uses a sequence of RGB images delivered through an internal vehicle-mounted camera for egocentric vision. It takes as an input only two modes, that are past trajectories and scales of pedestrians, and delivers as an output the three most likely paths for each tracked pedestrian. Experimental evaluation of the proposed architecture on the JAAD, ETH/UCY and Stanford Drone datasets reveal that the M2P3 system is significantly superior to selected state-of-the-art solutions.
A preference-based approach to incorporate the "voice of the customer" in mass-market software product design
Authors: Naous Dana , Legner Christine
Published: January 2021

With mobile and cloud computing, the software industry has witnessed a shift from customer-specific systems to a mass-market scenario. Integrating the "voice of the customer" is a critical success factor for mass-market products, but remains a challenge given the heterogeneity and distribution of their users. Classical requirements engineering methods rely on close interactions to gather user requirements and feedback regarding product features. However, they are hardly applicable in mass market scenarios, and new methods are required to assist product managers in designing their products while taking into consideration the opinion of the mass. In this paper, we argue for using market research techniques as preference-based approach in software product management. Following method engineering guidelines, we develop a method component
1
that refines conjoint analysis for the use in software product management. We present the meta-model and procedure and demonstrate it in a study on secure cloud storage services. We evaluate the feasibility, usefulness and ease of use of method component with experts in the RE domain. We contribute to mass-market software product management domain through a method component that builds on detailed understanding of user preferences for successful product design.
At the Water's Edge: Coastal Settlement, Transformative Adaptation, and Well-Being in an Era of Dynamic Climate Risk
Authors: Solecki William , Friedman Erin
Published: January 2021

With accelerating climate change, US coastal communities are experiencing increased flood risk intensity, resulting from accelerated sea level rise and stronger storms. These conditions place pressure on municipalities and local residents to consider a range of new disaster risk reduction programs, climate resilience initiatives, and in some cases transformative adaptation strategies (e.g., managed retreat and relocation from highly vulnerable, low-elevation locations). Researchers have increasingly understood that these climate risks and adaptation actions have significant impacts on the quality of life, well-being, and mental health of urban coastal residents. We explore these relationships and define conditions under which adaptation practices will affect communities and residents. Specifically, we assess climate and environmental stressors, community change, and well-being by utilizing the growing climate change literature and the parallel social science literature on risk and hazards, environmental psychology, and urban geography work, heretofore not widely integrated into work on climate adaptation.
Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality
Authors: Balnis Joseph , Adam Alejandro P. , Chopra Amit , Chieng Hau C. , Drake Lisa A. , Martino Nina , Bossardi Ramos Ramon , Feustel Paul J. , Overmyer Katherine A. , Shishkova Evgenia , Coon Joshua J. , Singer Harold A. , Judson Marc A. , Jaitovich Ariel
Published: January 2021

The COVID19 pandemic has caused more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to patients without COVID19 ARDS and others observing substantial differences. Moreover, although a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape’s association with mortality in patients with COVID19 ARDS. Even though the circulating leukocytes’ transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from patients with COVID19 are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality, whereas RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.
Natural Killer T Cells in Various Mouse Models of Hepatitis
Authors: Guan Jun , Wang Gang , Yang Qin , Chen Chao , Deng Jingwen , Gu Xinyu , Zhu Haihong
Published: January 2021

Natural killer T (NKT) cells are a key component of innate immunity. Importantly, a growing body of evidence indicates that NKT cells play an integral role in various acute and chronic liver injuries. NKT cells participate in the progression of an injury through the secretion of cytokines, which promote neutrophil infiltration and enhance Fas ligand (FasL) and granzyme‐mediated NKT cytotoxic activity. Therefore, examining the role of NKT cells in hepatic disease is critical for a comprehensive understanding of disease pathogenesis and may provide insight into novel approaches for treatment. For more than a century, mouse models that imitate the physiopathological conditions of human disease have served as a critical tool in biological and medical basic research, including studies of liver disease. Here, we review the role of NKT cells in various mouse models of hepatitis.
Generalized Orthogonal Discrete W Transform and Its Fast Algorithm
Authors: Sun Jichao , Zhang Zhengping
Published: January 2021

Based on the generalized discrete Fourier transform, the generalized orthogonal discrete W transform and its fast algorithm are proposed and derived in this paper. The orthogonal discrete W transform proposed by Zhongde Wang has only four types. However, the generalized orthogonal discrete W transform proposed by us has infinite types and subsumes a family of symmetric transforms. The generalized orthogonal discrete W transform is a real-valued orthogonal transform, and the real-valued orthogonal transform of a real sequence has the advantages of simple operation and facilitated transmission and storage. The generalized orthogonal discrete W transforms provide more basis functions with new frequencies and phases and hence lead to more powerful analysis and processing tools for communication, signal processing, and numerical computing.
Use of Network Pharmacology to Investigate the Mechanism by Which Allicin Ameliorates Lipid Metabolism Disorder in HepG2 Cells
Authors: Cheng Bijun , Li Tianjiao , Li Fenglin
Published: January 2021

Allicin has been well documented to exhibit a wide spectrum of biological activities, especially lipid-lowering activity, as a promising candidate for the management of nonalcoholic fatty liver disease (NALFD). However, the mechanisms underlying the therapeutic effects of allicin require further investigation. It is tempting to think of combining network pharmacology and experimental validation to investigate the mechanism by which allicin ameliorates lipid metabolism disorder in HepG2 cells. We established a cell model of hepatic steatosis induced by PA to investigate the antisteatotic effects of allicin. The studies showed that allicin reduced PA-induced lipid accumulation using Nile red staining and TC and TG assays. Then, 219 potential targets of allicin were successfully predicted by PharmMapper. According to Reactome Pathway Analysis, 44 potential targets related to lipid metabolism were screened out. Molecular signaling cascades mediated by allicin included PPARA, PPARG, FABP4, and FABP6 by cytoHubba and qPCR analysis. Results revealed that allicin activated the gene expression of PPARA and FABP6 and suppressed the gene expression of FABP4 and PPARG. Thus, the present study united the methods of network pharmacology and experimental validation to investigate the protein targets of allicin on PA-induced lipid metabolism disorders to supply a reference for related application for the first time.
Inhibition of PD‐1 Protects against TNBS‐Induced Colitis via Alteration of Enteric Microbiota
Authors: Xu Hao-ming , Zhou You-lian , Xu Jing , Li Ying-fei , Zhao Chong , Huang Hong-li , Du Yan-lei , He Jie , Zhou Yong-jian , Nie Yu-qiang
Published: January 2021

Background and Aim. The enteric microbiota is able to cross‐talk with factors involved in the blockade of programmed cell death protein 1 (PD‐1) and also plays an important role in the predisposition and onset of inflammatory bowel disease (IBD). The current study used a mouse model of experimental colitis to determine the pathogenic connection between PD‐1 inhibition, gut microbiota, and IBD. Methods. Colitis was induced in mice using 2,4,6‐trinitrobenzene‐sulfonic acid (TNBS), and mice were subsequently treated with either a PD‐1 inhibitor or 5‐amino‐salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high‐throughput 16S rRNA sequencing of fecal samples from the experimental mice. Results. TNBS caused mice to experience IBD‐like symptoms, which were attenuated by the PD‐1 inhibitor, as indicated by a decrease in DAI scores (p = 0.0002). Furthermore, in this mouse model of IBD, PD‐1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short‐chain fatty acid‐ (SCFA‐) producing bacteria of the Firmicutes (p < 0.05) and Bacteroidetes (p < 0.05) phyla but depopulated Proteobacteria (p < 0.05). Conclusion. PD‐1 inhibition can partly mitigate TNBS‐induced colitis and restore the enteric microbiota by enriching the abundance of SCFA‐producing bacteria.
Comparable Effects of Strontium Ranelate and Alendronate Treatment on Fracture Reduction in a Mouse Model of Osteogenesis Imperfecta
Authors: Shi Changgui , Sun Bin , Ma Chao , Wu Huiqiao , Chen Rui , He Hailong , Zhang Ying
Published: January 2021

Alendronate (Aln) has been the first‐line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three‐week‐old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR‐ and Aln‐treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.
MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome
Authors: Yu Rong , Liu Lv , Li Ya-Li , Fan Liang-Liang
Published: January 2021

Waardenburg syndrome (WS) is a group of rare genetic disorders characterized by hearing loss, changes in coloring of hair, skin, and eyes, and alterations in the shape of the face. Tietz syndrome is another rare disorder which presented similar phenotypes to WS. Patients with Tietz/Waardenburg syndrome often present with pale blue eyes, albino skin, and distinctive hair coloring, such as a patch of white hair or hair that prematurely turns gray. At present, more than six candidate genes are responsible for four types of Waardenburg syndrome and Tietz syndrome. This study is aimed at identifying the pathogenic gene variants in a three‐generation Han Chinese family with hearing loss, blue‐gray iris, albino skin, and white hair. In order to discover the molecular genetic lesion underlying the disease phenotype, whole exome sequencing in the proband, with Tietz/Waardenburg syndrome phenotypes, of a Han Chinese family from HeBei, China, was conducted. A novel heterozygous c.650G>C/p.Arg217Thr variant in melanocyte inducing transcription factor (MITF) was identified. Sanger sequencing further validated that this mutation existed in three affected individuals and absent in healthy family members. Bioinformatics analysis predicted that this mutation was deleterious. Our study further identified the genetic lesion of the family. Simultaneously, our study may also contribute to genetic counseling, embryonic screening of in vitro fertilized embryos, and prenatal genetic diagnosis of patients with Tietz/Waardenburg syndrome, especially for the proband, unmarried and unpregnant women, to reduce familial transmission in this Han Chinese family.
Effect of b Value on Imaging Quality for Diffusion Tensor Imaging of the Spinal Cord at Ultrahigh Field Strength
Authors: Bao Shu-Sheng , Zhao Can , Bao Xing-Xing , Rao Jia-Sheng
Published: January 2021

Objective. To explore the optimal b value setting for diffusion tensor imaging of rats’ spinal cord at ultrahigh field strength (7 T). Methods. Spinal cord diffusion tensor imaging data were collected from 14 rats (5 healthy, 9 spinal cord injured) with a series of b values (200, 300, 400, 500, 600, 700, 800, 900, and 1000 s/mm2) under the condition that other scanning parameters were consistent. The image quality (including image signal‐to‐noise ratio and image distortion degree) and data quality (i.e., the stability and consistency of the DTI‐derived parameters, referred to as data stability and data consistency) were quantitatively evaluated. The min‐max normalization method was used to process the calculation results of the four indicators. Finally, the image and data quality under each b value were synthesized to determine the optimal b value. Results. b = 200 s/mm2 and b = 900 s/mm2 ranked in the top two of the comprehensive evaluation, with the best image quality at b = 200 s/mm2 and the best data quality at b = 900 s/mm2. Conclusion. Considering the shortcomings of the ability of low b values to reflect the microstructure, b = 900 s/mm2 can be used as the optimal b value for 7 T spinal cord diffusion tensor scanning.