bluuebunny/crossref_metadata_2025 huggingface dataset:
A pooled analysis of patients with wound infections in the Phase 3 REVIVE trials: randomized, double-blind studies to evaluate the safety and efficacy of iclaprim versus vancomycin for treatment of acute bacterial skin and skin structure infections
Authors: Noviello Stephanie , Corey G. Ralph , Holland Thomas L. , Lodise Thomas , O’Riordan William , Wilcox Mark H. , File Thomas M. , Dryden Matthew , Balser Barbara , Scaramucci Amy , Torres Antoni , Huang David B.
Published: March 2020

Introduction. Iclaprim is a diaminopyrimidine antibiotic for the treatment of acute bacterial skin and skin structure infections (ABSSSI) due to Gram-positive pathogens.

Aim. This analysis evaluates patients with wound infections from two Phase 3 trials of ABSSSI.

Methodology. Six-hundred-two patients with wound infections from two Phase 3, double-blinded, randomized, multicenter, active controlled trials (REVIVE-1/–2) were evaluated in a post hoc analysis of iclaprim 80 mg compared with vancomycin 15 mg kg–1 administered intravenously every 12 h for 5–14 days. The primary endpoint was to determine whether iclaprim was non-inferior (10 % margin) to vancomycin in achieving a ≥20 % reduction from baseline in lesion size 48–72 h after starting study drug (early clinical response [ECR]). Safety was assessed.

Results. In REVIVE-1, ECR was 83.5 % with iclaprim versus 79.7 % with vancomycin (treatment difference 3.77%, 95 % CI −4.50%, 12.04%). In REVIVE-2, ECR was 82.7 % with iclaprim versus 76.3 % with vancomycin (treatment difference 6.38%, 95 % CI −3.35%, 16.12%). In the pooled dataset, iclaprim had similar ECR rates compared with vancomycin among wound infection patients (83.2 % vs 78.2 %) with a treatment difference of 5.01 % (95 % CI −1.29%, 11.32%). The safety profile was similar in iclaprim- and vancomycin-treated patients, except for a higher incidence of diarrhea with vancomycin (n=17) compared with iclaprim (n=6) and fatigue with iclaprim (n=17) compared with vancomycin (n=8).

Conclusion. Based on early clinical response, iclaprim achieved non-inferiority to vancomycin with a similar safety profile in patients with wound infections suspected or confirmed as caused by Gram-positive pathogens. Iclaprim may be a valuable treatment option for wound infections.
GENOMIC CHARACTERISATION AND PHYLOGENETIC ANALYSIS OF SARS-COV-2 IN ITALY
Authors: Zehender Gianguglielmo , Lai Alessia , Bergna Annalisa , Meroni Luca , Riva Agostino , Balotta Claudia , Tarkowski Maciej , Gabrieli Arianna , Bernacchia Dario , Rusconi Stefano , Rizzardini Giuliano , Antinori Spinello , Galli Massimo
Published: March 2020

This report describes the isolation, the molecular characterization and the phylogenetic analysis of the first three complete genomes of SARS-CoV-2 isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.
Development and Evaluation of an Android-based Platform for Early MCI Detection in an Elderly Population
Authors: Roozrokh Arshadi Montazer Mahsa , Zahediannasb Roohollah , Sharifian Roxana , Tahamtan Mahshid , Nasiri Mahdi , Nami Mohammad
Published: March 2020

Background

Mild cognitive impairment (MCI) is an intermediate stage of cognitive decline fitting in-between normal cognition and dementia. With the growing aging population, this study aimed to develop and psychometrically validate an android-based application for early MCI detection in elderly subjects.

Method

This study was conducted in two phases, including 1-Initial design and prototyping of the application named M-Check, 2-psychometric evaluation. After the design and development of the M-Check app, it was evaluated by experts and elderly subjects. Face validity was determined by two checklists provided to the expert panel and the elderly subjects. Convergent validity of the M-Check app was assessed using the Montreal Cognitive Assessment (MoCA) battery through Pearson correlation. Test-retest and internal consistency and reliability were evaluated using Intra-Class Correlation (ICC) and Kuder-Richardson coefficients, respectively. In addition, the usability was assessed by a System Usability Scale (SUS) questionnaire. SPSS 16.0 was employed to analyze the data.

Result

The app’s usability assessment by elderlies and experts scored 77.11 and 82.5, respectively. Also, the correlation showed that the M-Check app was negatively correlated with the MoCA test (r = -0.71, p <0.005), and the ICC was more than 0.7. Moreover, the Richardson’s Coder coefficient was 0.82, corresponding to an acceptable reliability.

Conclusion

In this study, we validated the M-Check app for the detection of MCI based on the growing need for cognitive assessment tools that can identify early decline. Such screeners are expected to take much shorter time than typical neuropsychological batteries do. Additional work are yet to be underway to ensure that M-Check is ready to launch and used without the presence of a trained person.
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Authors: Gautret Philippe , Lagier Jean-Christophe , Parola Philippe , Hoang Van Thuan , Meddeb Line , Mailhe Morgane , Doudier Barbara , Courjon Johan , Giordanengo Valérie , Vieira Vera Esteves , Dupont Hervé Tissot , Honoré Stéphane , Colson Philippe , Chabrière Eric , Scola Bernard La , Rolain Jean-Marc , Brouqui Philippe , Raoult Didier
Published: March 2020

Background

Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads.

Patients and methods

Patients were included in a single arm protocol to receive 600mg of hydroxychloroquine daily and their viral load in nasal swabs was tested daily. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.

Results

Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.

Conclusion

Hydroxychloroquine is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
Roles of meteorological conditions in COVID-19 transmission on a worldwide scale
Authors: Chen Biqing , Liang Hao , Yuan Xiaomin , Hu Yingying , Xu Miao , Zhao Yating , Zhang Binfen , Tian Fang , Zhu Xuejun
Published: March 2020

The novel coronavirus (SARS-CoV-2/2019-nCoV) identified in Wuhan, China, in December 2019 has caused great damage to public health and economy worldwide with over 140,000 infected cases up to date. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/provinces in Italy, 21 cities/provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken for modeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation (r2>0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future 12 days in several high-latitude cities with potential outbreak. This model could provide more information for government’s future decisions on COVID-19 outbreak control.
A comprehensive analysis of dominant and recessive parkinsonism genes in REM sleep behavior disorder
Authors: Mufti Kheireddin , Rudakou Uladzislau , Yu Eric , Ruskey Jennifer A. , Asayesh Farnaz , Laurent Sandra B. , Spiegelman Dan , Arnulf Isabelle , Hu Michele T.M. , Montplaisir Jacques Y. , Gagnon Jean-François , Desautels Alex , Dauvilliers Yves , Gigli Gian Luigi , Valente Mariarosaria , Janes Francesco , Högl Birgit , Stefani Ambra , Holzknecht Evi , Sonka Karel , Kemlink David , Oertel Wolfgang , Janzen Annette , Plazzi Giuseppe , Antelmi Elena , Figorilli Michela , Puligheddu Monica , Mollenhauer Brit , Trenkwalder Claudia , Sixel-Döring Friederike , De Cock Valérie Cochen , Monaca Christelle Charley , Heidbreder Anna , Ferini-Strambi Luigi , Dijkstra Femke , Viaene Mineke , Abril Beatriz , Boeve Bradley F. , Postuma Ronald B. , Rouleau Guy A. , Gan-Or Ziv
Published: March 2020

Objective

To examine the role of autosomal dominant (AD) and recessive (AR) Parkinsonism genes in the risk of isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD).

Methods

Ten genes implicated in AD and AR Parkinsonism were fully sequenced using targeted next-generation sequencing in 1,039 iRBD patients and 1,852 controls of European ancestry. These include the AR genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7 and PLA2G6, and the AD genes LRRK2, GCH1 and VPS35. To examine the role of rare heterozygous variants in these genes, burden test and SKAT-O analyses were performed. The contribution of homozygous and compound heterozygous variants was further examined in the AR genes. Copy number variants (CNVs) in PRKN were tested in a subset of samples (n=374) using multiplex ligation-dependent probe amplification followed by analysis of all samples using ExomeDepth.

Results

We found no association between rare heterozygous variants in the tested genes and risk for iRBD. Several homozygous and compound heterozygous carriers were identified with variants of unknown significance, yet there was no overrepresentation in iRBD patients versus controls.

Conclusion

Our results do not support a major role for variants in PRKN, PARK7, PINK1, VPS13C, ATP13A2, FBXO7, PLA2G6, LRRK2, GCH1 and VPS35 in the risk of iRBD.
Increasing prevalence of HIV-1 Transmitted Drug Resistance in Portugal: implications for first line treatment recommendations
Authors: Pingarilho Marta , Pimentel Victor , Diogo Isabel , Fernandes Sandra , Miranda Mafalda , Pineda-Pena Andrea , Libin Pieter , Theys Kristof , Martins M. Rosário O. , Vandamme Anne-Mieke , Camacho Ricardo , Gomes Perpétua , Abecasis Ana
Published: March 2020

Background

Treatment for all recommendations has allowed access to antiretroviral (ARV) treatment to an increasing number of patients. This minimizes transmission of infection but can potentiate the risk for development of transmitted drug resistance (TDR) and acquired drug resistance (ADR).

Objective

To study the trends of TDR and ADR in patients followed in Portuguese hospitals between 2001 and 2017.

Method

11911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutations according to the WHO surveillance list. Phenotypic resistance to ARV was evaluated with Standford HIVdb v7.0. Patterns of TDR, ADR and prevalence of mutations over time were analysed with logistic regression.

Results

The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (pfor-trend<0.001). This was due to a significant increase of both resistance mutations to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs) from 5.6% to 6.7% (pfor-trend=0.002) and 2.9% to 8.9% (pfor-trend<0.001), respectively. TDR to Protease Inhibitors decreased from 4.0% in 2003 to 2.2 in 2017 (pfor-trend=0.985). Paradoxically, the prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (pfor-trend<0.001) caused by a declining drug resistance to all ARV classes (pfor-trend<0.001).

Conclusions

While ADR is declining since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgent to develop public health programs to monitor levels and patterns of TDR in newly diagnosed patients.
Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2
Authors: Ni Ling , Ye Fang , Chen Meng-Li , Feng Yu , Deng Yong-Qiang , Zhao Hui , Wei Peng , Ge Jiwan , Li Xiaoli , Sun Lin , Wang Pengzhi , Liang Peng , Guo Han , Wang Xinquan , Qin Cheng-Feng , Chen Fang , Dong Chen
Published: March 2020

The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.
Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19)
Authors: Zhang Pingping , Gao Qi , Wang Tang , Ke Yuehua , Mo Fei , Jia Ruizhong , Liu Wanbing , Liu Lei , Zheng Shangen , Liu Yuzhen , Li Luping , Wang Yao , Xu Lei , Hao Kun , Yang Ruifu , Li Shiyue , Lin Changqing , Zhao Yong
Published: March 2020

Background

The colloidal gold immunochromatography assay (GICA) is a rapid diagnostic tool for novel coronavirus disease 2019 (COVID-19) infections. However, with significant numbers of false negatives, improvements to GICA are needed.

Methods

Six recombinant HCoV-19 nucleocapsid and spike proteins were prepared and evaluated. The optimal proteins were employed to develop a sandwich-format GICA strip to detect total antibodies (IgM and IgG) against HCoV-19. GICA’s performance was assessed with comparison of viral RNA detection.

Results

Recombinant HCoV-19 proteins were obtained, including three prokaryotically expressed rN, rN1, rN2 nucleocapsid proteins, and three eukaryotically expressed rS1, rS-RBD, rS-RBD-mFc spike proteins. The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) against coronavirus-specific IgM and IgG were chosen for GICA development. The GICA has a sensitivity and specificity of 86.89% (106/122) and 99.39% (656/660), respectively. Furthermore, 65.63% (21/32) of the clinically confirmed but RT-PCR negative samples were GICA positive.

Conclusions

The eukaryotically-expressed spike proteins (rS1and rS-RBD-mFc) are more suitable than the prokaryotically expressed nucleocapsid proteins for HCoV-19 serological diagnosis. The GICA sandwich used to detect total antibodies is a powerful complement to the current standard RNA-based tests.
Degree irregularity and rank probability bias in network meta-analysis
Authors: Davies Annabel L. , Galla Tobias
Published: March 2020

Network meta-analysis (NMA) is a statistical technique for the comparison of treatment options. The nodes of the network are the competing treatments and edges represent comparisons of treatments in trials. Outcomes of Bayesian NMA include estimates of treatment effects, and the probabilities that each treatment is ranked best, second best and so on. How exactly network geometry affects the accuracy and precision of these outcomes is not fully understood. Here we carry out a simulation study and find that disparity in the number of trials involving different treatments leads to a systematic bias in estimated rank probabilities. This bias is associated with an increased variation in the precision of treatment effect estimates. Using ideas from the theory of complex networks, we define a measure of ‘degree irregularity’ to quantify asymmetry in the number of studies involving each treatment. Our simulations indicate that more regular networks have more precise treatment effect estimates and smaller bias of rank probabilities. We also find that degree regularity is a better indicator of NMA quality than both the total number of studies in a network and the disparity in the number of trials per comparison. These results have implications for planning future trials. We demonstrate that choosing trials which reduce the network’s irregularity can improve the precision and accuracy of NMA outcomes.
Challenges of false positive and negative results in cervical cancer screening
Authors: Grimes David Robert , Corry Edward M.A. , Malagón Talía , O’Riain Ciaran , Franco Eduardo L. , Brennan Donal J.
Published: March 2020

Objective

To quantify the impact and accuracy of different screening approaches for cervical cancer, including liquid based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and their combinations via parallel co-testing and sequential triage. The secondary goal was to predict the effect of differing coverage rates of HPV vaccination on the performance of screening tests and in the interpretation of their results.

Design

Modelling study.

Main outcomes measured

Different screening modalities were compared in terms of number of cases of Cervical intra-epithelial neoplasia (CIN) grade 2 and 3 detected and missed, as well as the number of false positives leading to excess colposcopy, and number of tests required to achieve a given level of accuracy. The positive predictive value (PPV) and negative predictive value (NPV) of different modalities were simulated under varying levels of HPV vaccination.

Results

The model predicted that in a typical population, primary LBC screening misses 4.9 (95% Confidence Interval (CI) 3.5-CIN 2 / 3 cases per 1000 women, and results in 95 (95% CI: 93-97%) false positives leading to excess colposcopy. For primary HPV testing, 2.0 (95% CI: 1.9-2.1) cases were missed per 1000 women, with 99 (95% CI: 98-101) excess colposcopies undertaken. Co-testing markedly reduced missed cases to 0.5 (95% CI: 0.3-0.7) per 1000 women, but at the cost of dramatically increasing excess colposcopy referral to 184 per 1000 women (95% CI: 182-188). Conversely, triage testing with reflex screening substantially reduced excess colposcopy to 9.6 cases per 1000 women (95% CI: 9.3 - 10) but at the cost of missing more cases (6.4 per 1000 women, 95% CI: 5.1 - 8.0). Over a life-time of screening, women who always attend annual and 3-year co-testing were predicted to have a virtually 100% chance of falsely detecting a CIN 2 / 3 case, while 5 year co-testing has a 93.8% chance of a false positive over screening life-time. For annual, 3 year, and 5 year triage testing (either LBC with HPV reflex or vice versa), lifetime risk of a false positive is 35.1%, 13.4%, and 8.3% respectively. HPV vaccination rates adversely impact the PPV, while increasing the NPV of various screening modalities. Results of this work indicate that as HPV vaccination rates increase, HPV based screening approaches result in fewer unnecessary colposcopies than LBC approaches.

Conclusion

The clinical relevance of cervical cancer screening is crucially dependent upon the prevalence of cervical dysplasia and/or HPV infection or vaccination in a given population, as well as the sensitivity and specificity of various modalities. Although screening is life-saving, false negatives and positives will occur, and over-testing may cause significant harm, including potential over-treatment.
Double-Quencher Probes Improved the Detection Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by One-Step RT-PCR
Authors: Hirotsu Yosuke , Mochizuki Hitoshi , Omata Masao
Published: March 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerges in Wuhan City, Hubei Province, spreads worldwide, and threats the human life. The detection of SARS-CoV-2 is important for the prevention of the outbreak and management of patients. Real-time reverse-transcription polymerase chain reaction (RT-PCR) assay detected the virus in clinical laboratory.

Methods

This study utilized primers and single-quencher probes in accordance with the Centers for Disease Control and Prevention (CDC) in the USA and the National Institute of Infectious Diseases (NIID) in Japan. Moreover, we designed the double-quencher probes (YCH assay) according to the oligonucleotide sequence established by NIID. Using these assays, we conducted a one-step real-time RT-PCR with serial DNA positive control to assess the detection sensitivity.

Results

The threshold cycle (Ct) value of RT-PCR was relatively low in CDC and YCH assays compared to NIID assay. Serial dilution assay showed that both CDC and YCH assays could detect a low-copy number of DNA positive control. The background fluorescent signal at the baseline was lower in YCH than that of NIID.

Conclusion

Double-quencher probes decreased background fluorescent signal and improved detection sensitivity of SARS-CoV-2.
Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing
Authors: Hass Kenneth N. , Bao Mengdi , He Qian , Park Myeongkee , Qin Peiwu , Du Ke
Published: March 2020

A fully Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) system is developed for viral DNA detection. This powerful system is patterned with high-aspect ratio micropillars to enhance reporter probe binding. After surface modification and probe immobilization, CRISPR Cas12a/crRNA complex is injected into the fully enclosed system. With the presence of double-stranded DNA target, the CRISPR enzyme is activated and non-specifically cleaves the ssDNA reporters initially immobilized on the micropillars. This collateral cleavage releases fluorescence dyes into the assay, and the intensity is linearly proportional to the target DNA concentration ranging from 0.1 to 10 nM. Importantly, this system does not rely on traditional dye-quencher labeled probe thus eliminating the fluorescence background presented in the assay. Furthermore, our one-step detection protocol is performed at isothermal conditions (37°C) without using complicated and time-consuming off-chip probe hybridization and denaturation. This miniaturized and fully packed IMPACT chip demonstrates rapid, sensitive, and simple nucleic acid detection and is an ideal candidate for the next generation molecular diagnostic platform for point-of-care (POC) applications, responding to emerging and deadly pathogen outbreaks.
SARS-CoV-2 specific antibody responses in COVID-19 patients
Authors: Okba Nisreen M.A. , Müller Marcel A. , Li Wentao , Wang Chunyan , GeurtsvanKessel Corine H. , Corman Victor M. , Lamers Mart M. , Sikkema Reina S. , de Bruin Erwin , Chandler Felicity D. , Yazdanpanah Yazdan , Le Hingrat Quentin , Descamps Diane , Houhou-Fidouh Nadhira , Reusken Chantal B. E. M. , Bosch Berend-Jan , Drosten Christian , Koopmans Marion P.G. , Haagmans Bart L.
Published: March 2020

A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.
Incidence of Microbial Infections in English UK Biobank Participants: Comparison with the General Population
Authors: Hilton Bridget , Wilson Daniel , O’Connell Anne-Marie , Ironmonger Dean , Rudkin Justine K , Allen Naomi , Oliver Isabel , Wyllie David
Published: March 2020

Understanding the genetic and environmental risk factors for serious bacterial infections in ageing populations remains incomplete. Utilising the UK Biobank (UKB), a prospective cohort study of 500,000 adults aged 40-69 years at recruitment (2006-2010), could help address this.

We assess the feasibility of linking an England-wide dataset of microbiological isolations to UKB participants, to enable characterisation of microbial infections within the UKB Cohort. Microbiological infections occurring in patients in England, as recorded in the Public Health England Second Generation Surveillance System (SGSS), were linked to UKB participants using pseudonymised identifiers. By January 2015, ascertainment of laboratory reports from UKB participants by SGSS was estimated at 98%. 4.5% of English UKB participants had a positive microbiological isolate in 2015. Half of UKB isolates came from 12 laboratories, and 70% from 21 laboratories. Incidence rate ratios for microbial isolation, which is indicative of serious infection, from the UKB cohort relative to the comparably aged general population ranged from 0.6 to 1, compatible with the previously described healthy participant bias in UKB.

Data on microbial isolations can be linked to UKB participants from January 2015 onwards. This linked data would offer new opportunities for research into infectious disease in older individuals.
Buprenorphine treatment of opioid dependence: analysis of individual patient data
Authors: Bergen Andrew W , Baurley James W , Ervin Carolyn M , McMahan Christopher S , Bible Joe , Stafford Randall S , Mudumbai Seshadri C , Saxon Andrew J
Published: March 2020

Background

The efficacy and safety of buprenorphine alone and in combination with naloxone for treatment of opioid dependence were evaluated in Federally-sponsored randomized clinical trials. Meta-analysis of pooled individual participant data provides an opportunity to identify multiple predictors of buprenorphine treatment outcome.

Methods

We selected six buprenorphine efficacy and safety trials from NIDA’s Data Share database for analysis. Treatment, sociodemographic, and drug use history variable domains were systematically harmonized and included in analysis. After exclusions, 3,022 participants randomized or enrolled in buprenorphine treatment for opioid dependence (mean (SD) age 36.1 (9.8) years, 33% female, 66% White, 16% Hispanic, 14% Black), were analyzed using a generalized linear mixed model with time-weighted treatment variables and participant covariates. We defined positive urinalysis or self-reported lapse as the primary outcome.

Results

Four treatment variables were significantly associated (p < 0.001) with lapse. Time-weighted dose and time-weighted adaptive dose had greater estimated effects than time-in-trial and time-weighted clinic visit. All treatment variables were novel predictors of lapse.

Conclusions

In a large cohort of trial participants treated with buprenorphine and behavioral counseling for opioid dependence, we identified and ranked four novel treatment factors reflecting components of buprenorphine dose, clinical provider engagement and patient engagement. Additional research to explore the effects of pharmacologic and non- pharmacologic treatment factors, and to explore relations with provider and patient factors will help our understanding of buprenorphine treatment outcomes. Continued analyses of publicly available data will extend discovery and support development of personalized opioid use disorder treatments.

Highlights (3 to 5 bullet point max 85 characters each including spaces)

Treatment and participant variables were harmonized in six buprenorphine trials

Time-weighted treatment variables were used in a random effects mixed model of lapse

Buprenorphine dose and three clinical interactions were protective against lapse

Support of protective treatment factors may improve buprenorphine treatment success
Dynamic profile of severe or critical COVID-19 cases
Authors: Xu Yang
Published: March 2020

In December 2019, a cluster of acute respiratory illness, now known as SARS-CoV-2 pneumonia, occurred in Wuhan, China. World Health Organization (WHO) declared the rapidly spreading coronavirus outbreak a pandemic on March 11, 2020, acknowledging what has seemed clear for some time — the virus will likely spread to all countries on the globe. As of February 11, 2020, the Chinese Center for Disease Control and Prevention (China CDC) has officially reported that there are 2.0% (889) asymptomatic cases, 2.3% (1,023) death cases, and 80.9% mild cases among 44,672 confirmed cases. 51.4% (22,981) were male and 48.6% (21,691) were female. Lymphopenia, in particular T lymphopenia, was common among patients with SARS-COV-2 in the observation. A notable drop in CD4 and CD8 lymphocyte counts occurred early in the course of the syndrome and was associated with adverse outcomes. The appearing a phenomenon of lymphocyte depletion (PLD) suggested severe adverse outcomes. The outcome observed: 60% had discharged and 20% had die.
Facing small and biased data dilemma in drug discovery with federated learning
Authors: Xiong Zhaoping , Cheng Ziqiang , Xu Chi , Lin Xinyuan , Liu Xiaohong , Wang Dingyan , Luo Xiaomin , Zhang Yong , Qiao Nan , Zheng Mingyue , Jiang Hualiang
Published: March 2020

Artificial intelligence (AI) models usually require large amounts of high-quality training data, which is in striking contrast to the situation of small and biased data faced by current drug discovery pipelines. The concept of federated learning has been proposed to utilize distributed data from different sources without leaking sensitive information of these data. This emerging decentralized machine learning paradigm is expected to dramatically improve the success of AI-powered drug discovery. We here simulate the federated learning process with 7 aqueous solubility datasets from different sources, among which there are overlapping molecules with high or low biases in the recorded values. Beyond the benefit of gaining more data, we also demonstrate federated training has a regularization effect making it superior than centralized training on the pooled datasets with high biases. Further, two more cases are studied to test the usability of federated learning in drug discovery. Our work demonstrates the application of federated learning in predicting drug related properties, but also highlights its promising role in addressing the small data and biased data dilemma in drug discovery.
Fidgetin-like 2 is a novel negative regulator of axonal growth and can be targeted to promote functional nerve regeneration after injury
Authors: Baker Lisa , Tar Moses , Villegas Guillermo , Charafeddine Rabab , Kramer Adam , Vafaeva Olga , Nacharaju Parimala , Friedman Joel , Davies Kelvin P. , Sharp David J.
Published: March 2020

The microtubule (MT) cytoskeleton plays a critical role in axon growth and guidance. Here, we identify the MT severing enzyme fidgetin-like 2 (FL2) as a negative regulator of axonal regeneration and a potential therapeutic target for promoting neural regeneration after injury. Genetic knockout of FL2 in cultured adult dorsal root ganglion (DRG) neurons resulted in longer axons and attenuated growth cone retraction in response to inhibitory molecules. Given the axonal growth-promoting effects of FL2 depletionin vitro, we tested whether the enzyme could be targeted to promote regeneration in a rodent model of peripheral nerve injury. In the model used in our experiments, the cavernous nerves (CN) are either crushed or transected, mimicking nerve injury caused by radical prostatectomy (RP). As with patients, CN injury results in erectile dysfunction, for which there are presently poor treatment options. At the time of injury, FL2-siRNA or control-siRNA was applied to the site using nanoparticles or chondroitin sulfate microgels as delivery agents. Treatment significantly enhanced functional nerve recovery, as determined by cavernosometry (measurements of corporal blood pressure in response to electrostimulation of the nerve). Remarkably, following complete bilateral nerve transection, visible and functional nerve regeneration was observed in 7 out of 8 animals treated with FL2-siRNA. In contrast, no control-siRNA treated animals showed regeneration. These observations suggest a novel therapeutic approach to treat peripheral nerve injury, particularly injuries resulting from surgical procedures such as RP, where treatments depleting FL2 could be applied locally at the time of injury.
Development of Project Risk Management framework based on Industry 4.0 technologies
Authors: Rane Santosh B. , Potdar Prathamesh Ramkrishana , Rane Suraj
Published: March 2020

Purpose

The purpose of this paper is to identify the risks involved in the construction project based on a literature survey (LS), to develop a project risk management (PRM) framework based on Industry 4.0 technologies and to demonstrate the developed framework using Internet of Things (IoT) technology.

Design/methodology/approach

A comprehensive LS was carried out to know the different risks involved in the construction project and developed a PRM framework based on Industry 4.0 technologies to increase the effectiveness and efficiency of PRM. Heavy equipment and parameters were identified to demonstrate the developed framework based on IoT technology of Industry 4.0.

Findings

This paper demonstrates Industry 4.0 in the various stages of PRM. LS has identified 21 risks for a construction project. The demonstration of the PRM framework has identified the sudden breakdown of equipment and uncertainty of equipment as one of the critical risks associated with heavy equipment of construction project.

Research limitations/implications

The project complexity and features may add a few more risks in PRM.

Practical implications

The PRM framework based on Industry 4.0 technologies will increase the success rate of the project. It will enhance the efficiency and effectiveness of PRM.

Originality/value

The developed framework is helpful for the effective PRM of construction projects. The demonstration of PRM framework using IoT technology provides a logical way to manage risk involved in heavy equipment used in a construction project.
A closer look at determinants of organizational capability to innovate (OCI)
Authors: Montreuil Véra-Line , Lauzier Martin , Gagnon Stéphane
Published: March 2020

Purpose

The purpose of this paper is to provide a portrait of the main managerial and organizational determinants of organizational capability to innovate (OCI). Despite its importance, research on the subject seems limited, and little attempt has been made, over the years, to offer an in-depth and simultaneous analysis of these particular determinants, as well as an exploration of the underlying and complex mechanisms explaining their relationships to OCI.

Design/methodology/approach

A systematic review of articles published between 1991 and 2018 was conducted in ProQuest (ABI/INFORM Collection) and Scopus databases. A total of 64 articles were selected and analysed through the use of a coding grid.

Findings

Results highlight five key OCI determinants, namely: leadership, support, communication, culture, and learning. By using the dynamic capabilities theory (DCT) as a framework, this research suggests ways to better understand the dynamic action of these determinants as well as their contributions to OCI. Findings also suggest that OCI should be defined at the confluence of three perspectives (human, procedural and environmental aspects) to embrace the multiple facets of this complex construct. Proposals for future research are provided on how OCI can be better examined.

Originality/value

This research helps to understand the five core determinants through an integrated and holistic view and represents the first attempt to systematically analyse the scientific literature on OCI through the DCT lens.
A hidden deterioration in equal pay achievements?
Authors: Galanaki Eleanna
Published: March 2020

Purpose

Employee benefits, a critical element of total employee rewards, are important for both employers and employees. This study aims to explore the utility of employee benefits for male and female employees during the recent economic recession. In doing so, it intends to highlight an indirect deterioration of employment arrangements and equality in the workplace.

Design/methodology/approach

The paper draws on the findings of three repeated large-scale surveys during the Greek crisis (2012-2015, totalN= 3,498).

Findings

Employees report that the availability of employee benefits has decreased during the recession and that women find more utility in them than men do. Additionally, women seem to be affected more than men by decreases in employee benefits allocation.

Research limitations/implications

The present findings support calls for contingent employee reward allocation.

Practical implications

Employers wishing to sustain their competitive advantage by fostering inclusion and diversity and/or employers with a high female employee ratio are encouraged to consider increasing their employee benefits portfolio.

Social implications

The recent economic crisis and the subsequent recession have brought about several potential negative effects, in terms of the employment conditions for women. Decreased employee benefits are a hidden negative effect of the recession for female employees and it presents multiple, potential and unforeseen consequences for gender diversity and inclusion.

Originality/value

To the best of the author’s knowledge, this is the first study to address non-monetary employee remuneration under the lens of gender pay differentials. It does so in a turbulent macro-economic setting.
An 80-year projection of nZEB strategies in extreme climatic conditions of Iraq
Authors: Al-saeed Yahya Wisam , Ahmed Abdullahi , Pärn Erika Anneli
Published: March 2020

Purpose

The Middle Eastern terrain is expected to encounter unprecedented climatic conditions before the turn of the next century (circa. 80 years), emanating from extreme heat waves that exceed the critical threshold of habitable conditions. This threatens to cause a significant challenge that is exacerbated by a gap between the supply and demand of affordable energy. Therefore, the purpose of this study is to investigate the potential of utilising nearly zero-energy buildings (nZEB) to improve the performance of residential buildings in Iraq and the Middle East.

Design/methodology/approach

This study uses Iraq as a case-study because of the breadth of climatic conditions experienced across its wide-reaching territory and also because of the recent critical infrastructural challenges following the geo-political crisis. Three virtual buildings were simulated for Baghdad, Mosul and Basra cities to narrow the confines of the region to achieve nZEB under current and future climatic weather scenarios.

Findings

The findings showed that in all three cases studies, the buildings located within the three climatic regions in Iraq could achieve both significant annual energy reductions as well as nZEB standards which could range from 41 per cent to 87 per cent for current climatic conditions and 40 per cent to 84 per cent by 2080. An analysis has also been carried out for the three case-study cities which revealed significant operational-cost savings achievable through nZEB buildings.

Originality/value

There are currently limited studies that investigate such positive potential for nZEB strategies under the current and predicted future climatic scenarios in the Middle East.
Industrial tourism: moderating effects of commitment and readiness on the relationship between tourist experiences and perceived souvenir value
Authors: Lin Chien-Hsin
Published: March 2020

Purpose

The purpose of this study is to propose that in-factory experiences transfer into souvenir evaluation, and the process is moderated by customers’ commitment and readiness cumulated in daily life.

Design/methodology/approach

The study collected data from 398 tourists of tea leaves tourism factories.

Findings

The results reveal that interactive experience is a dominant determinant of perceived souvenir value. Interactive and hedonic experiences reinforce each other to create perceived souvenir value. Low commitment diverts customers to emphasize hedonic experience, whereas low readiness constraints customers’ resources, and hence, depreciates value delivered from interactive experience.

Research limitations/implications

Intrinsic hedonic values are weaker predictors than extrinsic ones for perceived value in a leisure tourism setting. Merchandize quality is perceived and judged together with interpersonal interactions in the industrial tourism contexts, instead of objectively evaluating by customers themselves.

Practical implications

The experience or credence attribute of tea leaves is difficult for ordinary customers to evaluate, leaving most of the consumption value to be fostered by the firm. Perceived souvenir value could transfer to routinized purchase behavior, it is more imperative turning initial tourists into committed loyal customers by relationship management strategies than merely creating hedonic surroundings.

Originality/value

The study contributions are twofold: first, the study extends the influence of tourist experience to the perceived souvenir value; second, the study verifies the interaction effects of in-factory experiences and customer roles on perceived souvenir value.
North Korea’s emerging martial arts tourism: a Taekwon-Do case study
Authors: Cynarski Wojciech Jan , Johnson John Arthur
Published: March 2020

Purpose

This descriptive, non-experiment case study addresses the little-studied topic of martial arts tourism within the Democratic People’s Republic of Korea (DPRK; i.e., North Korea) to determine if it is a form of non-entertainment tourism.

Design/methodology/approach

The current research focusses on a single subject (Singaporean female; 36 years of age (at time of interview); Taekwon-Do 4th degree black belt) who travelled to the DPRK three times to practice the Korean martial art Taekwon-Do. After the initial contact, a questionnaire was used and direct interviews via Skype and Facebook were performed. A broad thematic discourse, as well as analysis of the subject’s travel and practice notes and photographs from her stay in the DPRK, were also incorporated into the findings.

Findings

The subject developed new Taekwon-Do skills, which permitted her to obtain higher Taekwon-Do ranks as well as enriched her personality and changed certain conceptions. Self-realization and self-improvement through martial arts are the dominant motives of martial arts tourism. Therefore, the subject’s motivation confirms martial arts tourism can be a variation of non-entertainment tourism.

Research limitations/implications

This research is hindered by the standard case study limitations: it is difficult to generalize this study’s results to the wider DPRK population, the interviewee’s and researchers’ subjective feelings may have influenced the findings, and selection bias is definitely a factor because of the study’s population being a single female of non-DPRK origin.

Originality/value

As one of the first studies on DPRK martial arts tourism and practice, this research examines where research on the DPRK and martial arts tourism intersect. It is thusly unique in providing new insights into the DPRK’s intention for its tourism industry, as well as Taekwon-Do, arguably its most marketable cultural asset.
Decay, dirt and backwardness: interpretations of the socialist heritage in Hungary by first and later generation Australian-Hungarians
Authors: Andits Petra
Published: March 2020

Purpose

The purpose of this paper is to contrasts the ways in which first and later generation Australian-Hungarians respond to dirt and decay in the physical environment of Hungary during their journeys there. Given the growing trend of diaspora tourism, it is now more important than ever to consider tourism at the level of tourist subjectivity.

Design/methodology/approach

The material stems from multi-sited ethnographic research in two distinct periods.

Findings

In particular, the paper argues that, while the first generation relies on images internalized in the diaspora and the youngsters rely heavily on a popular Western backpacker discourse, they both share an orientalistic view of Hungary.

Originality/value

This paper aims to energize greater discussion about, and debate over, the connectivity between diasporas and tourism. In attempting to merge the two disciplines, the meta-narratives that have influenced the different generations’ perceptions are analyzed.
Methodology of integrated knowledge in Islamic economics and finance: collective ijtihād
Authors: Rafikov Ildus , Akhmetova Elmira
Published: March 2020

Purpose

The purpose of this paper is to discuss the methodology of integrated knowledge in Islamic economics and finance and seek to offer collective ijtihād as one way to find solutions to the existing problems in the field.

Design/methodology/approach

The study is based on the idea of multidisciplinarity or interdisciplinarity, which uses not only traditional sources of Islam and economics, such as uṣūl al-fiqh, fiqh mu’amalat, econometrics, statistics, microeconomics and macroeconomics but also looks into behavioural and natural sciences for inspiration and solutions. This paper is constructed using the methodology of “the two readings”, as promoted by the International Institute of Islamic Thought, and which combines the revealed and the existential sciences.

Findings

This paper proposes the collaborative multidisciplinary methodology as the main approach to studying the modern problems and challenges, as well as for finding solutions in the fields of Islamic economics and finance.

Practical implications

Studying and researching issues, particularly in the field of Islamic economics and finance, from an interdisciplinary perspective, effectively broadens practical applications and possibilities in Islamic finance.

Originality/value

This paper contributes to social sciences, especially the field of Islamic finance, and calls upon researchers to engage in multidisciplinary studies.