bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropilin-1 is a host factor for SARS-CoV-2 infection
Authors: Daly James L. , Simonetti Boris , Klein Katja , Chen Kai-En , Williamson Maia Kavanagh , Antón-Plágaro Carlos , Shoemark Deborah K. , Simón-Gracia Lorena , Bauer Michael , Hollandi Reka , Greber Urs F. , Horvath Peter , Sessions Richard B. , Helenius Ari , Hiscox Julian A. , Teesalu Tambet , Matthews David A. , Davidson Andrew D. , Collins Brett M. , Cullen Peter J. , Yamauchi Yohei
Published: October 2020

Another host factor for SARS-CoV-2

Virus-host interactions determine cellular entry and spreading in tissues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the earlier SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a receptor; however, their tissue tropism differs, raising the possibility that additional host factors are involved. The spike protein of SARS-CoV-2 contains a cleavage site for the protease furin that is absent from SARS-CoV (see the Perspective by Kielian). Cantuti-Castelvetri
et al.
now show that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial and epithelial cells. Daly
et al.
found that the furin-cleaved S1 fragment of the spike protein binds directly to cell surface NRP1 and blocking this interaction with a small-molecule inhibitor or monoclonal antibodies reduced viral infection in cell culture. Understanding the role of NRP1 in SARS-CoV-2 infection may suggest potential targets for future antiviral therapeutics.

Science
, this issue p.
856
, p.
861
; see also p.
765
Lymph nodes: The cradle for antitumor immunity
Authors: Shi Lewis Z.
Published: October 2020

Tumor-draining lymph nodes control tumor-specific immune responses induced by anti–PD-L1 therapy.
Experimental Evolution Identifies Adaptive Aneuploidy as a Mechanism of Fluconazole Resistance in Candida auris
Authors: Bing Jian , Hu Tianren , Zheng Qiushi , Muñoz José F. , Cuomo Christina A. , Huang Guanghua
Published: October 2020

Candida auris
is a newly emerging fungal pathogen of humans and has attracted considerable attention from both the clinical and basic research communities. Clinical isolates of
C. auris
are often resistant to one or more antifungal agents. To explore how antifungal resistance develops, we performed experimental evolution assays using a fluconazole-susceptible isolate of
C. auris
(BJCA001). After a series of passages through medium containing increasing concentrations of fluconazole, fungal cells acquired resistance.
All Treatment Parameters Affect Environmental Surface Sanitation Efficacy, but Their Relative Importance Depends on the Microbial Target
Authors: Cai Shiyu , Phinney David M. , Heldman Dennis R. , Snyder Abigail B.
Published: October 2020

Commercial food manufacturers commonly employ a single sanitation program that addresses both bacterial pathogen and fungal spoilage microbiota, despite the fact that the two microbial targets respond differently to various environmental sanitation conditions. Comparison of outcome-based clusters of treatment combinations may facilitate the development of compensatory sanitation regimes where longer contact time or greater force are applied so that lower sanitizer concentrations can be used. Determination of microbiological outcomes related to sanitation program efficacy against a panel of treatment conditions allows food processors to balance tradeoffs between quality and safety with cost and waste stream management, as appropriate for their facility.
MgrA Activates Staphylococcal Capsule via SigA-Dependent Promoter
Authors: Lei Mei G. , Lee Chia Y.
Published: October 2020

The virulence of
Staphylococcus aureus
depends on the expression of various virulence factors, which is governed by a complex regulatory network. We have been using capsule as a model virulence factor to study virulence gene regulation in
S. aureus
. MgrA is one of the regulators of capsule and has a major effect on capsule production. However, how MgrA regulates capsule genes is not understood. In this study, we were able to define the mechanism involving MgrA regulation of capsule. In addition, we also delineated the role of MgrA in capsule regulatory pathways involving the key virulence regulators Agr and Arl. This study further advances our understanding of virulence gene regulation in
S. aureus
, an important human pathogen.
Distinct Fecal and Plasma Metabolites in Children with Autism Spectrum Disorders and Their Modulation after Microbiota Transfer Therapy
Authors: Kang Dae-Wook , Adams James B. , Vargason Troy , Santiago Marina , Hahn Juergen , Krajmalnik-Brown Rosa
Published: October 2020

Despite the prevalence of autism and its extensive impact on our society, no U.S. Food and Drug Administration-approved treatment is available for this complex neurobiological disorder. Based on mounting evidences that support a link between autism and the gut microbiome, we previously performed a pioneering open-label clinical trial using intensive fecal microbiota transplant. The therapy significantly improved gastrointestinal and behavioral symptoms. Comprehensive metabolomic measurements in this study showed that children with autism spectrum disorder (ASD) had different levels of many plasma metabolites at baseline compared to those in typically developing children. Microbiota transfer therapy (MTT) had a systemic effect, resulting in substantial changes in plasma metabolites, driving a number of metabolites to be more similar to those from typically developing children. Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers.
Withholding or withdrawing life-sustaining treatment in extremely low gestational age neonates
Authors: Dworetz April R , Natarajan Girija , Langer John , Kinlaw Kathy , James Jennifer R , Bidegain Margarita , Das Abhik , Poindexter Brenda , Bell Edward F , Cotten C M , Kirpalani Haresh , Shankaran Seetha , Stoll Barbara J ,   the Eunice Kennedy Shriver National Institute of Child Health
Published: October 2020

Objective

To identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates.

Design

Observational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres on neonates born at 22–28 weeks gestation who died >12 hours through 120 days of age during 2011–2016. Sociodemographic and clinical factors were compared between infants who died following WWLST and without WWLST.

Results

Of 1168 deaths, 67.1% occurred following WWLST. Withdrawal of assisted ventilation (97.4%) was the primary modality. WWLST rates were inversely proportional to gestational age. Life-sustaining treatment was withheld or withdrawn more often for non-Hispanic white infants than for non-Hispanic black infants (72.7% vs 60.4%; 95% CI 1.00 to 1.92) or Hispanic infants (72.7% vs 67.2%; 95% CI 1.32 to 3.72). WWLST rates varied across centres (38.6–92.6%; p<0.001). The centre with the highest rate had adjusted odds 4.89 times greater than the average (95% CI 1.18 to 20.18). The adjusted odds of WWLST were higher for infants with necrotiing enterocolitis (OR 1.77, 95% CI 1.21 to 2.59) and severe brain injury (OR 1.98, 95% CI 1.44 to 2.74).

Conclusions

Among infants who died, WWLST rates varied widely across centres and were associated with gestational age, race, ethnicity, necrotiing enterocolitis, and severe brain injury. Further exploration is needed into how race, centre, and approaches to care of infants with necrotiing enterocolitis and severe brain injury influence WWLST.
Risk of non-infectious uveitis or myasthenia gravis in patients on checkpoint inhibitors in a large healthcare claims database
Authors: Xia Tian , Brucker Alexander J , McGeehan Brendan , VanderBeek Brian L
Published: October 2020

Aim

To determine if checkpoint inhibitors (CPIs) confer an increased risk of non-infectious uveitis or myasthenia gravis (MG) compared to patients on non-checkpoint inhibitor (N-CPI) chemotherapy.

Methods

A retrospective cohort study was performed comparing patients in a large commercial and Medicare advantage database exposed to CPI compared to N-CPI. All patients who initiated a CPI (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab and durvalumab) were eligible. Date of earliest CPI in the exposure group and N-CPI chemotherapy in the comparator group was considered the index date. Exclusion occurred in both cohorts for any history of uveitis or MG diagnosis and having <1 year in the insurance plan prior to the index date, and <6 months in plan following the index date. Every exposed patient was matched up to 1:10 based on demographics and index year to patients on N-CPI chemotherapy. Multivariate Cox proportional hazards regression modelling was performed.

Results

For evaluation of incidence of non-infectious uveitis, 26 (0.3%) of 8678 patients on CPI and 123 (0.2%) of 76 153 N-CPI comparators were found to have non-infectious uveitis. After multivariate analysis, CPIs showed an increased hazard for uveitis compared to N-CPI (HR=2.09; 95% CI 1.36 to 3.22, p=0.001). For the MG analysis, 11 (0.1%) of 9210 patients developed MG in the CPI group and 36 (0.04%) of 80 620 comparators. The CPI cohort had a higher hazard of developing MG (HR=2.60; 95% CI 1.34 to 5.07, p=0.005) compared to controls in multivariate analysis.

Conclusions

Exposure to CPI confers a higher risk for non-infectious uveitis and MG compared to N-CPI chemotherapy.
Outcomes of intravitreal methotrexate to salvage eyes with relapsed primary intraocular lymphoma
Authors: Mohammad Mona , Andrews Richard M , Plowman P Nicholas , Hay Gordon , Arora Amit K , Cohen Victoria M L , Sagoo Mandeep S
Published: October 2020

Purpose

To report the outcomes of intravitreal methotrexate (MTX) injections to rescue eyes with relapsed primary intraocular lymphoma (PIOL).

Methods

Retrospective case series of patients with ocular relapse of PIOL who had initially received systemic chemotherapy (all five cases) and external beam radiotherapy (EBRT) to brain and orbits (two cases). Injections of MTX (400 µg/0.1 mL) were given one time per week for 1 month, every other week for 4 months, followed by a maintenance phase of one injection one time per month for 8 months (total of 20 injections in a year).

Results

From April 2008 to February 2016, there were nine eyes of five patients (three men; average age at first presentation 62 years) treated with our rescue protocol of intravitreal MTX injections. Ocular relapse occurred at a mean interval of 15 months (range 5–34 months) after the completion of initial systemic treatment. At mean follow-up of 31 months (range 5–104 months), tumour control was achieved in eight out of nine eyes (89%); one eye failed, with persistent retinal infiltrates despite increasing the frequency of injections, resulting in severe keratopathy. The only other complication occurred in one eye, developing cystoid macular oedema from MTX injections that resolved with topical anti-inflammatory medications and reduced frequency of MTX. There were no cases of reduced vision or ocular relapse, but two patients died (one of central nervous system lymphoma).

Conclusions

Intravitreal MTX was a safe and effective treatment modality for relapsed PIOL after systemic chemotherapy and radiotherapy, achieving local tumour control in 89%, and hence represents an optimal choice. However, given the rare nature of PIOL, larger collaborative studies with longer follow-up are needed to corroborate this.
Ten-year time trends in preterm birth during a sociodemographic transition period: a retrospective cohort study in Shenzhen, China
Authors: Ma Rui , Luo Yali , Wang Jun , Zhou Yanxia , Sun Haiyang , Ren Xi , Xu Quan , Zhang Lian , Zou Lingyun
Published: October 2020

Objectives

To investigate time trends of preterm birth and estimate the contributions of risk factors to the changes in preterm birth rates over a decade (2009–2018) of transitional period in Shenzhen, China.

Design

Retrospective cohort study between 2009 and 2018.

Setting

All births in Baoan during January 2009 and December 2018 registered in the Shenzhen Birth Registry Database.

Participants

478 044 live births were included with sociodemographic and medical records for both women and infants.

Outcome measures

The incidence rate of preterm birth stratified by different maternal and infant characteristics. Multiple logistic regression was used to identify significant risk factors associated with preterm birth. The population attributable risk fraction of each factor was calculated to estimate its contribution to variations of preterm birth rate over the 10 years.

Results

A total of 27 829 preterm births from 478 044 (5.8%) live births were recorded and the preterm birth rate increased from 5.5% in 2009 to 6.2% in 2018. Medically induced preterm birth rate increased from 2.0% in 2009 to 3.4% in 2018 while spontaneous preterm labour rate decreased from 3.3% to 2.7% over the decade years. Risk factors including multiple pregnancy (0.28% increase) drove the rise of preterm birth rate, whereas changes in maternal educational attainment (0.22% reduction) and prenatal care utilisation (0.45% reduction) had contributed to the decline in preterm birth rate.

Conclusions

An uptrend of preterm birth rate was observed in an area under rapid sociodemographic transitions during 2009–2018 and the changes were associated with these sociodemographic transitions. Continued investments in girls’ education and prenatal care have the potential of reducing preterm birth rate.
(Rad 8)Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial)
Authors: Oliphant Elizabeth Anne , McKinlay Christopher J D , McNamara David G , Alsweiler Jane Marie
Published: October 2020

Introduction

Infants born late preterm (34+0 to 36+6 weeks’ gestational age) have frequent episodes of intermittent hypoxaemia compared with term infants. Caffeine citrate reduces apnoea and intermittent hypoxaemia and improves long-term neurodevelopmental outcomes in infants born very preterm and may have similar effects in late preterm infants. Clearance of caffeine citrate increases with gestational age and late preterm infants are likely to need a higher dose than very preterm infants. Our aim is to determine the most effective and best-tolerated dose of caffeine citrate to reduce transient intermittent hypoxaemia events in late preterm infants.

Methods and analysis

A phase IIB, double-blind, five-arm, parallel, randomised controlled trial to compare the effect of four doses of oral caffeine citrate versus placebo on the frequency of intermittent hypoxaemia. Late preterm infants will be enrolled within 72 hours of birth and randomised to receive 5, 10, 15 or 20 mg/kg/day caffeine citrate or matching placebo daily until term corrected age. The frequency of intermittent hypoxaemia (events/hour where oxygen saturation concentration is ≥10% below baseline for ≤2 min) will be assessed with overnight oximetry at baseline, 2 weeks after randomisation (primary outcome) and at term corrected age. Growth will be measured at these timepoints, and effects on feeding and sleeping will be assessed by parental report. Data will be analysed using generalised linear mixed models.

Ethics and dissemination

This trial has been approved by the Health and Disability Ethics Committees of New Zealand (reference 18/NTA/129) and the local institutional research review committees. Findings will be disseminated to peer-reviewed journals to clinicians and researchers at local and international conferences and to the public. The findings of the trial will inform the design of a large multicentre trial of prophylactic caffeine in late preterm infants, by indicating the most appropriate dose to use and providing information on feasibility.

Trial registration number

ACTRN12618001745235; Pre-results.
Osseointegrated reconstruction and rehabilitation of transtibial amputees: the Osseointegration Group of Australia surgical technique and protocol for a prospective cohort study
Authors: Haque Russel , Al-Jawazneh Shakib , Hoellwarth Jason , Akhtar Muhammad Adeel , Doshi Karan , Tan Yao Chang , Lu William Yenn-Ru , Roberts Claudia , Al Muderis Munjed
Published: October 2020

Introduction

Lower extremity amputation uniformly impairs a person’s vocational, social and recreational capacity. Rehabilitation in traditional socket prostheses (TSP) is associated with a spectrum of complications involving the socket-residuum interface which lead to reduced prosthetic use and quality of life. Osseointegration has recently emerged as a novel concept to overcome these complications by eliminating this interface and anchoring the prosthesis directly to bone. Though the complications of TSPs affect both transfemoral and transtibial amputees, Osseointegration has been predominantly performed in transfemoral ones assuming a greater benefit/risk ratio. However, as the safety of the procedure has been established, we intend to extend the concept to transtibial amputees and document the outcomes.

Methods and analysis

This is protocol for a prospective cohort study, with patient enrolment started in 2014 and expected to be completed by 2022. The inclusion criteria are age over 18 years, unilateral, bilateral and mixed transtibial amputation and experiencing socket-related problems. All patients receive osseointegrated implants, the type of which depend on the length of the residuum and quality of bone, which are press-fitted into the residual bone. Objective functional outcomes comprising 6-Minute Walk Test, Timed Up-and-Go test and K-level, subjective patient-reported-quality-of-life outcomes (Short Form Health Survey 36, daily prosthetic wear hours, prosthetic wear satisfaction) and adverse events are recorded preoperatively and at postoperative follow-up intervals of 3, 6, 12 months and yearly, and compared with the preoperative values using appropriate statistical tests. Multivariable multilevel logistic regression will be performed with a focus to identify factors associated with outcomes and adverse events, specifically infection, periprosthetic fracture, implant fracture and aseptic loosening.

Ethics and dissemination

The Ethics approval for the study has been received from the University of Notre Dame, Sydney, Australia (014153S). The outcomes of this study will be disseminated by publications in peer-reviewed academic journals and scientific presentations at relevant orthopaedic conferences.
Maternal age at delivery and risk of allergy and asthma in the offspring: a systematic review and meta-analysis protocol
Authors: Amera Yohannes Tesfaye , Baldeh Abdoulie K , Ali Mohamed Mustafa , Goksör Emma , Wennergren Göran , Nwaru Bright I
Published: October 2020

Introduction

While several perinatal factors have been linked to the risk of developing asthma and allergy in childhood, the role of maternal age at delivery remains uncertain. Some studies suggest that young maternal age at delivery may increase the risk, while other studies suggested a reduced risk. To provide a clearer appreciation of the underlying evidence, we plan to undertake a systematic review to synthesise previous studies that have investigated the association between maternal age at delivery and the risk of asthma and allergy in the offspring.

Methods and analysis

We will search PubMed, EMBASE, ISI Web of Science, Scopus and Google Scholar to identify relevant studies on the topic published in the databases from inception until October 2020. We will search databases of proceedings of international conferences, contact authors who have published on the topic and search the reference lists of the included studies in order to identify additional studies. Two investigators will independently screen the identified studies, perform data extraction and examine the risk of bias in the studies; a third investigator will arbitrate throughout these processes. We will use the Effective Public Health Practice Project tool for assessment of the risk of bias in included studies. We will perform random-effects meta-analysis to combine effect estimates from included studies judged to be homogeneous.

Ethics and dissemination

Only data from the published literature will be included in this study, therefore no ethics approval is required. Our findings will be published in a peer-reviewed journal.

Protocol registration

The protocol has been submitted for registration on PROSPERO, University of York, and Centre for Review and Dissemination, now awaiting the assignment of a registration number.
External validation of the DIVA and DIVA3 clinical predictive rules to identify difficult intravenous access in paediatric patients
Authors: Girotto Cristian , Arpone Marta , Frigo Anna Chiara , Micheletto Matteo , Mazza Alessandro , Da Dalt Liviana , Bressan Silvia
Published: October 2020

Background

Intravenous (IV) peripheral access is often a difficult procedure in the paediatric ED, causing pain and significant distress. Clinical prediction tools including reproducible variables have been developed to help clinicians identify children at risk of difficult IV access, likely to need additional resources/interventions to maximise success at first attempt. We aimed to externally validate the Difficult IntraVenous Access (DIVA) and DIVA3 scores developed for this purpose.

Methods

Cross-sectional study of children undergoing IV cannulation by nurses in a tertiary-care paediatric ED. Data were collected at the time of the procedure in a clinical report form.

Results

Of 440 children included (56.8% males; median age 4.7 years (IQR 1.5–9.5)), 23.4% had a difficult IV access (defined as requiring >1 attempt). Diagnostic accuracy measures for a DIVA cut-off ≥4 and their 95% CIs were sensitivity 24.3% (16.4% to 33.7%), specificity 92.6% (89.2% to 95.1%), positive and negative predictive value 50.0% (35.3% to 64.5%) and 80.0% (75.7% to 83.9%), respectively. The same measures for the DIVA3 were 22.3% (14.7% to 31.6%), 93.5% (90.3% to 95.9%), 51.1% (35.8% to 66.3%) and 79.8% (75.4% to 83.6%). The area under the receiver operating characteristic curve was 0.652 (95% CI 0.591 to 0.712) for the DIVA and 0.649 (95% CI 0.589 to 0.709) for the DIVA3 score. In patients with DIVA and DIVA3 <4, nurses’ prediction of greater difficulty in IV placement and moderate/severe dehydration were common independent predictors of difficult IV at multivariate analysis. Only nurses’ prediction of greater difficulty in IV placement were associated with higher odds of difficult cannulation for both DIVA/DIVA3 scores ≥4.

Conclusion

We externally validated the DIVA and DIVA3 showing a similar accuracy compared with the DIVA derivation cohort and between DIVA and DIVA3. We identified factors that can help refine further the risk of difficult IV access and support decision making on the best strategy to maximise the chances of cannulation success on first attempt.
Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism
Authors: Sano Makoto , Takahashi Ryota , Ijichi Hideaki , Ishigaki Kazunaga , Yamada Tomoharu , Miyabayashi Koji , Kimura Gen , Mizuno Suguru , Kato Hiroyuki , Fujiwara Hiroaki , Nakatsuka Takuma , Tanaka Yasuo , Kim Jinsuk , Masugi Yohei , Morishita Yasuyuki , Tanaka Mariko , Ushiku Tetsuo , Nakai Yousuke , Tateishi Keisuke , Ishii Yukimoto , Isayama Hiroyuki , Moses Harold L , Koike Kazuhiko
Published: October 2020

Objective

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox).

Design

Presence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed.

Results

We found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p<0.01).

Conclusion

Blocking VCAM-1/sVCAM-1 might be a potent therapeutic approach for PDAC as well as CAT, which can contribute to the prognosis. Increase of plasma ANP and sVCAM-1 might be a diagnostic approach for CAT in PDAC.
Effect of IBD medications on COVID-19 outcomes: results from an international registry
Authors: Ungaro Ryan C , Brenner Erica J , Gearry Richard B , Kaplan Gilaad G , Kissous-Hunt Michele , Lewis James D , Ng Siew C , Rahier Jean-Francois , Reinisch Walter , Steinwurz Flávio , Underwood Fox E , Zhang Xian , Colombel Jean-Frederic , Kappelman Michael D
Published: October 2020

Objective

We sought to evaluate COVID-19 clinical course in patients with IBD treated with different medication classes and combinations.

Design

Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of IBD patients with confirmed COVID-19. We used multivariable regression with a generalised estimating equation accounting for country as a random effect to analyse the association of different medication classes with severe COVID-19, defined as intensive care unit admission, ventilator use and/or death.

Results

1439 cases from 47 countries were included (mean age 44.1 years, 51.4% men) of whom 112 patients (7.8%) had severe COVID-19. Compared with tumour necrosis factor (TNF) antagonist monotherapy, thiopurine monotherapy (adjusted OR (aOR) 4.08, 95% CI 1.73 to 9.61) and combination therapy with TNF antagonist and thiopurine (aOR 4.01, 95% CI 1.65 to 9.78) were associated with an increased risk of severe COVID-19. Any mesalamine/sulfasalazine compared with no mesalamine/sulfasalazine use was associated with an increased risk (aOR 1.70, 95% CI 1.26 to 2.29). This risk estimate increased when using TNF antagonist monotherapy as a reference group (aOR 3.52, 95% CI 1.93 to 6.45). Interleukin-12/23 and integrin antagonists were not associated with significantly different risk than TNF antagonist monotherapy (aOR 0.98, 95% CI 0.12 to 8.06 and aOR 2.42, 95% CI 0.59 to 9.96, respectively).

Conclusion

Combination therapy and thiopurines may be associated with an increased risk of severe COVID-19. No significant differences were observed when comparing classes of biologicals. These findings warrant confirmation in large population-based cohorts.

MKH should be changed to MDK for co-last author line
Multiple arterial coronary bypass grafting is associated with greater survival in women
Authors: Tam Derrick Y , Rocha Rodolfo V , Fang Jiming , Ouzounian Maral , Chikwe Joanna , Lawton Jennifer , Ko Dennis T , Austin Peter C , Gaudino Mario , Fremes Stephen E
Published: October 2020

Objective

Multiple arterial grafting (MAG) in coronary artery bypass grafting (CABG) is associated with higher survival and freedom from major adverse cardiac and cerebrovascular events (MACCEs) in observational studies of mostly men. It is not known whether MAG is beneficial in women. Our objectives were to compare the long-term clinical outcomes of MAG versus single arterial grafting (SAG) in women undergoing CABG for multivessel disease.

Methods

Clinical and administrative databases for Ontario, Canada, were linked to obtain all women with angiographic evidence of left main, triple or double vessel disease undergoing isolated non-emergent primary CABG from 2008 to 2019. 1:1 propensity score matching was performed. Late mortality and MACCE (composite of stroke, myocardial infarction, repeat revascularisation and death) were compared between the matched groups with a stratified log-rank test and Cox proportional-hazards model.

Results

2961 and 7954 women underwent CABG with MAG and SAG, respectively, for multivessel disease. Prior to propensity-score matching, compared with SAG, those who underwent MAG were younger (66.0 vs 68.9 years) and had less comorbidities. After propensity-score matching, in 2446 well-matched pairs, there was no significant difference in 30-day mortality (1.6% vs 1.8%, p=0.43) between MAG and SAG. Over a median and maximum follow-up of 5.0 and 11.0 years, respectively, MAG was associated with greater survival (HR 0.85, 95% CI 0.75 to 0.98) and freedom from MACCE (HR 0.85, 95% CI 0.76 to 0.95).

Conclusions

MAG was associated with greater survival and freedom from MACCE and should be considered for women with good life expectancy requiring CABG.
The contribution of changes to tax and social security to stalled life expectancy trends in Scotland: a modelling study
Authors: Richardson Elizabeth , Taulbut Martin , Robinson Mark , Pulford Andrew , McCartney Gerry
Published: October 2020

Background

Life expectancy (LE) improvements have stalled, and UK tax and welfare ‘reforms’ have been proposed as a cause. We estimated the effects of tax and welfare reforms from 2010/2011 to 2021/2022 on LE and inequalities in LE in Scotland.

Methods

We applied a published estimate of the cumulative income impact of the reforms to the households within Scottish Index of Multiple Deprivation (SIMD) quintiles. We estimated the impact on LE by applying a rate ratio for the impact of income on mortality rates (by age group, sex and SIMD quintile) and calculating the difference between inflation-only changes in benefits and the reforms.

Results

We estimated that changes to household income resulting from the reforms would result in an additional 1041 (+3.7%) female deaths and 1013 (+3.8%) male deaths. These deaths represent an estimated reduction of female LE from 81.6 years to 81.2 years (−20 weeks), and male LE from 77.6 years to 77.2 years (−23 weeks). Cuts to benefits and tax credits were modelled to have the most detrimental impact on LE, and these were estimated to be most severe in the most deprived areas. The modelled impact on inequalities in LE was widening of the gap between the most and least deprived 20% of areas by a further 21 weeks for females and 23 weeks for males.

Interpretation

This study provides further evidence that austerity, in the form of cuts to social security benefits, is likely to be an important cause of stalled LE across the UK.
Trauma and depressive symptomatology in middle-aged persons at high risk of dementia: the PREVENT Dementia Study
Authors: Ritchie Karen , Carrière Isabelle , Gregory Sarah , Watermeyer Tam , Danso Samuel , Su Li , Ritchie Craig W , O'Brien John T
Published: October 2020

Objective

Depression and trauma are associated with changes in brain regions implicated in Alzheimer’s disease. The present study examined associations between childhood trauma, depression, adult cognitive functioning and risk of dementia.

Methods

Data from 378 participants in the PREVENT Dementia Study aged 40–59 years. Linear and logistic models were used to assess associations between childhood trauma, depression, dementia risk, cognitive test scores and hippocampal volume.

Results

Childhood trauma was associated with depression and reduced hippocampal volume but not current cognitive function or dementia risk. Poorer performance on a delayed face/name recall task was associated with depression. Childhood trauma was associated with lower hippocampal volume however poorer cognitive performance was mediated by depression rather than structural brain differences.

Conclusion

Depressive symptomatology may be associated with dementia risk via multiple pathways, and future studies should consider subtypes of depressive symptomatology when examining its relationship to dementia.
Transmuscular quadratus lumborum block for total laparoscopic hysterectomy: a double-blind, randomized, placebo-controlled trial
Authors: Hansen Christian , Dam Mette , Nielsen Martin Vedel , Tanggaard Katrine B , Poulsen Troels Dirch , Bendtsen Thomas Fichtner , Børglum Jens
Published: October 2020

Background

The population of patients scheduled for total laparoscopic hysterectomy at our surgical center is heterogeneous concerning a multitude of demographic variables such as age, collateral surgery and malign or benign pathogenesis. A common denominator is moderate to severe postoperative pain and a substantial opioid consumption. A recent procedure specific postoperative pain management (PROSPECT) review found no gain from the regional techniques included. The transmuscular quadratus lumborum (TQL) block has shown promising results in recent trials for other types of surgery. The aim of the current study was to investigate the analgesic efficacy of the ultrasound-guided TQL block for total laparoscopic hysterectomy.

Methods

We enrolled 70 patients and randomly allocated participants to preoperative bilateral ultrasound-guided TQL block with either 60 mL 0.375% ropivacaine or 60 mL isotonic saline. Preoperatively, all patients received the TQL block (active or placebo) as well as a standardized multimodal analgesic regimen consisting of oral paracetamol, ibuprofen and dexamethasone. Intraoperatively, intravenous sufentanil 0.2 µg/kg was administered 30 min prior to emergence.

Primary outcome

Opioid consumption during the first 12 postoperative hours.

Secondary outcomes

Pain scores, times to first opioid demand and first ambulation, nausea and vomiting, and total opioid consumption during the first 24 postoperative hours.

Results

No significant intergroup differences were observed for any outcome. Mean (SD) oral morphine equivalent consumption the first 12 postoperative hours was 58.4 mg (48.3) vs 62.9 mg (48.5), p=0.70, for group ropivacaine versus group saline.

Conclusion

Preoperative bilateral ultrasound-guided TQL block did not reduce opioid consumption after total laparoscopic hysterectomy.

Trial registration numbers

NCT 03650998, EudraCT (2017-004593-34).
Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation
Authors: Field John K , Vulkan Daniel , Davies Michael P A , Duffy Stephen W , Gabe Rhian
Published: October 2020

Background

Early detection of lung cancer saves lives, as demonstrated by the two largest published low-dose CT screening trials. Optimal implementation depends on our ability to identify those most at risk.

Methods

Version 2 of the Liverpool Lung Project risk score (LLPv2) was developed from case-control data in Liverpool and further adapted when applied for selection of subjects for the UK Lung Screening Trial. The objective was to produce version 3 (LLPv3) of the model, by calibration to national figures for 2017. We validated both LLPv2 and LLPv3 using questionnaire data from 75 958 individuals, followed up for lung cancer over 5 years. We validated both discrimination, using receiver operating characteristic (ROC) analysis, and absolute incidence, by comparing deciles of predicted incidence with observed incidence. We calculated proportionate difference as the percentage excess or deficit of observed cancers compared with those predicted. We also carried out Hosmer-Lemeshow tests.

Results

There were 599 lung cancers diagnosed over 5 years. The discrimination of both LLPv2 and LLPv3 was significant with an area under the ROC curve of 0.81 (95% CI 0.79 to 0.82). However, LLPv2 overestimated absolute risk in the population. The proportionate difference was −58.3% (95% CI −61.6% to −54.8%), that is, the actual number of cancers was only 42% of the number predicted.

In LLPv3, calibrated to national 2017 figures, the proportionate difference was −22.0% (95% CI −28.1% to −15.5%).

Conclusions

While LLPv2 and LLPv3 have the same discriminatory power, LLPv3 improves the absolute lung cancer risk prediction and should be considered for use in further UK implementation studies.
Cigarettes smoked among daily and non-daily smokers following CVS Health’s tobacco-free pharmacy policy
Authors: Phillips Aryn Z , Ahern Jennifer A , Kerr William C , Rodriguez Hector P
Published: October 2020

Introduction

In September 2014, CVS Health ceased tobacco sales in all of its 7700 pharmacies nationwide. We investigate the impact of the CVS policy on the number of cigarettes smoked per day among metropolitan daily and non-daily smokers, who may respond to the availability of smoking cues in different manners.

Methods

Data are from the US Census Bureau Tobacco Use Supplement to the Current Population Survey 2014–2015 and the Blue Cross and Blue Shield Institute Community Health Management Hub. Adjusted difference-in-difference (DID) regressions assess changes in the number of cigarettes smoked per day among daily smokers (n=10 759) and non-daily smokers (n=3055), modelling core-based statistical area (CBSA) level CVS pharmacy market share continuously. To assess whether the policy had non-linear effects across the distribution of CVS market share, we also examine market share using tertiles.

Results

CVS’s tobacco-free pharmacy policy was associated with a significant reduction in the number of cigarettes smoked by non-daily smokers in the continuous DID (rate ratio=0.985, p=0.022), with a larger reduction observed among non-daily smokers in CBSAs in the highest third of CVS market share compared with those living in CBSAs with no CVS presence (rate ratio=0.706, p=0.027). The policy, however, was not significantly associated with differential changes in the number of cigarettes by daily smokers.

Conclusion

The removal of tobacco products from CVS pharmacies was associated with a reduction in the number of cigarettes smoked per day among non-daily smokers in metropolitan CBSAs, particularly those in which CVS had a large pharmacy market share.
Computed tomographic and clinical findings in a dog with suspected liver lobe torsion, secondary disseminated intravascular coagulation and multiorgan infarction
Authors: Sumping Jessica C , O'Connell Erin M , Mortier Jeremy
Published: October 2020

A 9.5‐year‐old, neutered male, large crossbreed dog presented with unspecific clinical signs of lethargy, vomiting, anorexia and polydipsia. CT and blood analyses were consistent with liver lobe torsion with secondary disseminated intravascular coagulation causing renal and myocardial infarction and pulmonary thromboembolism. To the authors’ knowledge, this is the first case of a suspected liver lobe torsion displaying a ‘whirl sign’ and also the first CT description of a presumed myocardial infarction in a dog.
Real-time winter road surface condition monitoring using an improved residual CNN
Authors: Pan Guangyuan , Muresan Matthew , Yu Ruifan , Fu Liping
Published: October 2020

This paper proposes a real-time winter road surface condition (RSC) monitoring solution that automatically generates descriptive RSC information in terms of snow and ice coverage by using images from fixed traffic and weather cameras. Several state-of-the-art pre-trained deep neural networks are customized and fine-tuned to address a specific domain, classifying the amount of snow coverage on a road surface. A thorough evaluation is conducted to identify and select the best model. This evaluation uses an extensive set of experiments to test the accuracy and generalization of each model and uses transfer-learning to fine-tune each of the pre-trained models on independent images from different traffic and weather cameras. The transferability of each model, relationship between model performance and data size, and the system settings of each model are then examined. Lastly, three online weight calibration methods are proposed to automatically update the model in new environments. The result shows that re-training the model using images from a mixed set of cameras has the most promising results.
CDC Dorado yellow seed coat oilseed flax
Authors: Booker Helen M. , Rowland Gordon G. , Kutcher H. Randy , Rashid Khalid Y.
Published: October 2020

CDC Dorado is a yellow seed coat oilseed flax (Linum usitatissimum L.) registered in 2017 by the Crop Development Centre, University of Saskatchewan, Saskatoon, SK, Canada. This cultivar has a 7% higher yield than AC Nugget in the Black soil zone of the prairies coupled with a earlier maturity than Flanders across 10 site-years in western Canada. It has a medium (45.2%) oil content, high iodine value (204.2), an α-linolenic acid content of 64%, and a 1000-seed weight of 6.0 g. It is immune to flax rust caused by Melampsora lini (Ehrenb.) Thüm. and is moderately resistant to wilt and powdery mildew caused by Fusarium oxysporum Schltdl. f. sp. lini (Bolley) W.C. Snyder & H.N. Hansen and Oidium lini, respectively.
Experimental investigation on post-processed NiCr thermal barrier coating and its sliding wear behaviour
Authors: Srinivasan V. , Karuppuswamy P. , Velmurugan T. , Priyadharshini G. Suganya
Published: October 2020

NiCr metal is deposited on martensitic stainless steel using an atmospheric plasma spray method. To enrich the metallurgical properties of the NiCr metallic coating, a standard heat treatment process is adopted. From the investigation, it has been shown that the voids and porosity developed during the thermal spray have been controlled through heat treatment. Electron image analysis reveals that the coating has reduced porosity with strong and dense bonding strength. With reference to the surface hardness, the post-processed coating yields a maximum of 140 Hv compared with the coated (129 Hv) and base metal (115 Hv). Subsequently, the sliding wear behaviour of post-processed NiCr coating has a minimum wear of 25 μm for an applied load of 5 N and 57 μm for an applied load of 15 N. Owing to the high metallurgical bonding, the coating has sustained the heavy loads, and the wear formation is controlled. However, the base metal has an adhesive wear mechanism caused by the high frictional force on the sliding friction. Therefore, it is recommended that post-processed thermal barrier coatings possess good metallurgical bonding and withstand heavy load causing minimum wear.
Generalised radiating fields in Einstein–Gauss–Bonnet gravity
Authors: Brassel Byron P. , Maharaj Sunil D.
Published: October 2020

A five-dimensional spherically symmetric generalised radiating field is studied in Einstein–Gauss–Bonnet gravity. We assume the matter distribution is an extended Vaidya-like source and the resulting Einstein–Gauss–Bonnet field equations are solved for the matter variables and mass function. The evolution of the mass, energy density and pressure are then studied within the spacetime manifold. The effects of the higher order curvature corrections of Einstein–Gauss–Bonnet gravity are prevalent in the analysis of the mass function when compared to general relativity. The effects of diffusive transport are then considered and we derive the specific equation for which diffusive behaviour is possible. Gravitational collapse is then considered and we show that collapse ends with a weak and conical singularity for the generalised source, which is not the case in Einstein gravity.
Lie symmetry analysis, explicit solutions and conservation laws of the time fractional Clannish Random Walker’s Parabolic equation
Authors: Wang Panpan , Shan Wenrui , Wang Ying , Li Qianqian
Published: October 2020

In this paper, we mainly study the symmetry analysis and conservation laws of the time fractional Clannish Random Walker’s Parabolic (CRWP) equation. The vector fields and similarity reduction of the time fractional CRWP equation are obtained. In addition, based on the power series theory, a simple and effective approach for constructing explicit power series solutions is proposed. Finally, by use of the new conservation theorem, the conservation laws of the time fractional CRWP equation are constructed.
Triggering parametric-down conversion-based quantum key distribution via radiation field
Authors: Martin Tchoffo , Giresse Tene Alain , Yannick Djebayole Mimbe III
Published: October 2020

We discuss the influence of radiation field on the secure key size and the maximum safety distance during QKD by using a set of photons produced via a spontaneous parametric-down conversion (SPDC) photon source. Four implementations that use multiple-photons and decoy states are discussed, these include nondecoy state, infinite active decoy state, passive decoy state with threshold detector and passive decoy state with perfect photon-number resolving detector. Results show that the radiation field significantly improves both the secure key size and the maximum secure communication distance. Therefore, the radiation field is found to be a good candidate to reduce unwanted interactions of photons with the quantum channel and hence, to increase the secure key rate and the maximum safety distance between legitimate users.
Pseudospectral Time-Domain (PSTD) Methods for the Wave Equation: Realizing Boundary Conditions with Discrete Sine and Cosine Transforms
Authors: Wise Elliott S. , Jaros Jiri , Cox Ben T. , Treeby Bradley E.
Published: October 2020

Pseudospectral time domain (PSTD) methods are widely used in many branches of acoustics for the numerical solution of the wave equation, including biomedical ultrasound and seismology. The use of the Fourier collocation spectral method in particular has many computational advantages. However, the use of a discrete Fourier basis is also inherently restricted to solving problems with periodic boundary conditions. Here, a family of spectral collocation methods based on the use of a sine or cosine basis is described. These retain the computational advantages of the Fourier collocation method but instead allow homogeneous Dirichlet (sound-soft) and Neumann (sound-hard) boundary conditions to be imposed. The basis function weights are computed numerically using the discrete sine and cosine transforms, which can be implemented using [Formula: see text] operations analogous to the fast Fourier transform. Practical details of how to implement spectral methods using discrete sine and cosine transforms are provided. The technique is then illustrated through the solution of the wave equation in a rectangular domain subject to different combinations of boundary conditions. The extension to boundaries with arbitrary real reflection coefficients or boundaries that are nonreflecting is also demonstrated using the weighted summation of the solutions with Dirichlet and Neumann boundary conditions.