bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of SARS‐CoV‐2 nasopharyngeal swab PCR positivity in COVID‐19 convalescent plasma donors
Authors: Ikegami Sachie , Benirschke Robert , Flanagan Tara , Tanna Nicole , Klein Tovah , Elue Rita , Debosz Patricia , Mallek Jessica , Wright Gregory , Guariglia Perry , Kang Jason , Gniadek Thomas J.
Published: August 2020

Background

Nucleic acid persists after symptom resolution and infectivity for many viral infections via delayed clearance of nucleic acid fragments, non‐infectious particles, or transmissible virus. For Coronavirus Disease 2019 (COVID‐19), the relationship between nasopharyngeal (NP) swab positivity, the development of antibodies against COVID‐19, and clinical history are unclear.

Study design and methods

Individuals who recovered from COVID‐19 and volunteered to donate convalescent plasma (CP) were screened by NP swab PCR, responded to a questionnaire, and were tested for anti‐COVID‐19 antibodies.

Results

A proportion of 11.8% of individuals tested positive for SARS‐CoV‐2 by NP swab PCR greater than 14 days after the resolution of symptoms of active disease, including one donor who had asymptomatic disease and tested positive by NP swab 41 days after her initial diagnosis. Clinical history did not show a significant correlation with persistence of NP swab positivity. Also, NP swab positivity >14 days from symptom resolution did not correlate with anti‐COVID‐19 serology results. IgG anti‐SARS‐CoV‐2 spike antibody strength correlated with hospitalization for COVID‐19 using two different assays. Total anti‐SARS‐CoV‐2 nucleocapsid antibody strength correlated with time from symptom resolution to sample collection and symptom duration.

Conclusions

SARS‐CoV‐2 nucleic acid is detectable long after the resolution of symptoms in a significant percentage of previously diagnosed individuals, which is important to consider when interpreting PCR swab results. Persistence of PCR positivity does not correlate with antibody strength or symptoms of COVID‐19. If anti‐spike antibody is used to assess CP potency, individuals who suffered severe COVID‐19 disease symptoms may represent better donors.
Contrast‐enhanced ultrasound for sentinel lymph node mapping in the routine staging of canine mast cell tumours: A feasibility study
Authors: Fournier Quentin , Thierry Florence , Longo Maurizio , Malbon Alexandra , Cazzini Paola , Bisson Jocelyn , Woods Samantha , Liuti Tiziana , Bavcar Spela
Published: August 2020

Canine mast cell tumours (MCTs) typically spread to lymph nodes (LNs) before reaching distant sites, and LN assessment is an important part of MCT staging. Sentinel LN (SLN) mapping techniques to identify draining LNs are being developed and could improve the accuracy of MCT staging. The primary objective of this feasibility study was to determine the safety and effectiveness of contrast‐enhanced ultrasound (CEUS) to identify SLNs. Secondary objectives were to determine if the SLNs identified by CEUS coincided with the regional LN predicted by the anatomical lymphosomes, if previous MCT excision altered CEUS SLN findings, and if CEUS could identify MCT nodal metastases. Between June 2017 and March 2019, 59 dogs with 62 MCTs were enrolled. No adverse events related to CEUS were reported. CEUS detected at least 1 SLN in 59/62 MCTs (95.2%, 95% CI: 86.5‐99.0%). In only 32/59 (54.2%) MCTs, clinicians would have correctly predicted the SLN(s) identified by CEUS. Among the 35 MCTs that had histological examination of the SLN(s), the prevalence of metastasis was 60% (95% CI: 42.1‐76.1%). Additional staging procedures did not reveal any metastases in dogs with histologically non‐metastatic SLNs. Integration of CEUS SLN mapping into the routine staging of MCTs is promising, but future studies are required to refine this procedure and to investigate if it would translate into a clinical benefit.
Nonlinear Dynamic Modeling of a Robotic Endoscopy Platform on Synthetic Tissue Substrates
Authors: Formosa Gregory A. , Micah Prendergast J. , Sean Humbert J. , Rentschler Mark E.
Published: August 2020

A scaled robotic endoscopy platform (REP) was previously developed to efficiently test new control schemes in a simulated colon environment. This article presents the derivation and tuning of a nonlinear model of the REP operating on various substrates. The modeling technique and novel empirical friction profiling demonstrated here are useful for a wide variety of devices interacting with unconventional substrates. The model is first derived from the REP drivetrain inertial characteristics, and then the interaction with synthetic tissue is quantified by an automated traction measurement system for multiple substrates. The resulting model is then used with ground-truth VICON and sensor data to optimize uncertain parameters by minimizing pose error over a variety of tests and substrates. The results show an average error reduction of 67% over all tests and substrates, with a worst-case 10% open-loop final position error. The success of these results proves a robust dynamic model of the REP and its tissue interactions without the need to model complex and computationally expensive viscoelastic material properties or discrete/nonlinear events such as stalling. The resulting model will be used to develop model-based feedback control for estimation, disturbance rejection, and autonomy for the REP in an actuated colon simulator.
Long Term Dynamic Simulation of a Stem Cell Nucleus
Authors: Rabiei Manoochehr , McColloch Andrew , Rabbani Parisa , Cho Michael , Bowling Alan
Published: August 2020

Biomolecular simulations are computationally expensive. Simulating time histories larger than seconds remain elusive even with the help of supercomputers. Biological phenomena are multiscale in nature. The dynamics range from atomistic to microscale. Herein a recently developed scaling approach, based on the method of multiple scales (MMS), is used to accomplish a long term simulation of a subcellular system. The first key advantage of this approach is the drastic reduction in computational time. This approach is illustrated using a mesenchymal stem cell (MSC) as it undergoes adipogenic differentiation, a process that takes 15 days, which was simulated in less than 1.5 h on a typical desktop computer. The second key advantage of the high-speed simulation is that it facilitates the study of mechanical properties, such as nucleus membrane stiffness, that are difficult to measure experimentally with certainty.
Condition Monitoring of Motor-Gear System Dynamics With Rotor and Gear Faults
Authors: Bai Wenyu , Bao Guanjun , Qin Datong , Wang Yawen , Lim Teik C.
Published: August 2020

An electromechanical system consisting of an electric motor and planetary gear set is modeled and analyzed in this paper. The model integrates various internal excitations including time-varying gear mesh stiffness, nonlinear spatial effect and, saturation effect, and component flaws. The simulation results predict the effects of rotor and gear faults including broken rotor bar, rotor static and dynamic eccentricity, and tooth root crack of the gear on the electromechanical system behavior. It is verified as the results obtained are in accordance with the features derived within previous researches. Furthermore, new sidebands merged on the dynamic response spectra such as slip frequency harmonics, rotor rotational frequency harmonics, and fault-related rotational frequency harmonics can be applied to detect electrical and mechanical faults in the motor-gear system. This paper lays the foundation for the comprehensive further study of working condition monitoring for the motor-gear system.
Examination of Novice Coaches’ Previous Experience as Athletes: Examples of Autonomy Support and Controlling Behaviors as Influences on Future Coaching Practice
Authors: Benish Diane , Langdon Jody , Culp Brian
Published: August 2020

As part of a coach’s informal learning process, previous athletic experience is a foundational element of an athlete’s future coaching career, determining the perspectives, beliefs, and behaviors the coach will use in their interactions with athletes. Although it is investigated more generally, previous athletic experience is rarely considered in understanding specific coaching behaviors related to supporting athletes’ needs and motivation. This study investigated 15 novice coaches’ personal athletic and coaching experiences to determine how these experiences influenced their own coaching practice with regard to the engagement in autonomy-supportive and/or controlling behaviors. The interview data revealed that novice coaches used their past experiences to inform their practice in the following three ways: (a) experienced controlling behaviors as an athlete, which transferred to a desire to be more autonomy supportive in coaching; (b) experienced controlling behaviors as an athlete, which transferred to a desire to be more controlling in coaching; and (c) experienced autonomy-supportive behaviors as an athlete, which transferred to a desire to be more autonomy supportive in coaching. These results suggest the importance of considering previous athletic experience as an antecedent to coaches’ engagement in autonomy-supportive behaviors.
Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients
Authors: Zanella Marie-Céline , Cordey Samuel , Kaiser Laurent
Published: August 2020

Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients.
Cross-Reactivity, Epitope Mapping, and Potency of Monoclonal Antibodies to Class 5 Fimbrial Tip Adhesins of Enterotoxigenic Escherichia coli
Authors: Liu Yang , Shahabudin Sakina , Farid Sami , Lee Lanfong H. , McVeigh Annette L. , Maciel Milton , Poole Steven T. , Broadman Matthew , Prouty Michael G. , Savarino Stephen J.
Published: August 2020

Enterotoxigenic
Escherichia coli
(ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed to be a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of the class 5 fimbrial family being the best characterized. The eight related members of the ETEC class 5 fimbrial family are subdivided into three subclasses (5a, 5b, and 5c) that share similar structural arrangements, including a fimbrial tip adhesin.
Noncanonical Cell Death Induction by Reassortant Reovirus
Authors: Rodríguez Stewart Roxana M. , Raghuram Vishnu , Berry Jameson T. L. , Joshi Gaurav N. , Mainou Bernardo A.
Published: August 2020

TNBC is unresponsive to hormone therapies, leaving patients afflicted with this disease with limited treatment options. We previously engineered an oncolytic reovirus (r2Reovirus) with enhanced infective and cytotoxic properties in TNBC cells. However, how r2Reovirus promotes TNBC cell death is not known. In this study, we show that reassortant r2Reovirus can promote nonconventional caspase-dependent but caspase 3-independent cell death and that the mechanism of cell death depends on the genetic composition of the host cell. We also map the enhanced oncolytic properties of r2Reovirus in TNBC to interactions between a type 3 M2 gene segment and type 1 genes. Our data show that understanding the interplay between the host cell environment and the genetic composition of oncolytic viruses is crucial for the development of efficacious viral oncolytics.
Biodiverse
Histoplasma
Species Elicit Distinct Patterns of Pulmonary Inflammation following Sublethal Infection
Authors: Jones Grant S. , Sepúlveda Victoria E. , Goldman William E.
Published: August 2020

Acute pulmonary histoplasmosis in healthy individuals comprises most of the disease burden caused by the fungal pathogen
Histoplasma
. Fungal pneumonia is frequently delayed in diagnosis and treatment due to a prolonged period of quiescence early during infection. In this study, we used a murine respiratory model of histoplasmosis to investigate how different
Histoplasma
species modulate lung inflammation throughout the complete course of infection. We propose that a relatively low, sublethal inoculum is ideal to model acute pulmonary histoplasmosis in humans, primarily due to the quiescent stage of fungal growth that occurs in the lungs of mice prior to the initiation of inflammation. Our results reveal the unique course of lung immunity associated with divergent species of
Histoplasma
and imply that the progression of clinical disease is considerably more heterogeneous than previously recognized.
Gulf of Nuna: Astrochronologic correlation of a Mesoproterozoic oceanic euxinic event
Authors: Mitchell Ross N. , Kirscher Uwe , Kunzmann Marcus , Liu Yebo , Cox Grant M.
Published: August 2020

The ca. 1.4 Ga Velkerri and Xiamaling Formations, in Australia and the north China craton, respectively, are both carbonaceous shale deposits that record a prominent euxinic interval and were intruded by ca. 1.3 Ga dolerite sills. These similarities raise the possibility that these two units correlate, which would suggest the occurrence of widespread euxinia, organic carbon burial, and source rock deposition. Paleomagnetic data are consistent with Australia and the north China craton being neighbors in the supercontinent Nuna and thus permit deposition in a single large basin, and the putative stratigraphic correlation. However, lack of geochronological data has precluded definitive testing. The Xiamaling Formation has been shown to exhibit depositional control by orbital cycles. Here, we tested the putative correlation with the Velkerri Formation by cyclostratigraphic analysis. The Velkerri Formation exhibits sedimentological cycles that can be interpreted to represent the entire hierarchy of orbital cycles, according to a sedimentation rate that is consistent with Re-Os ages. Comparison of the inferred durations of the euxinic intervals preserved in both the Xiamaling and Velkerri Formations reveals a nearly identical ∼10-m.y.-long oceanic euxinic event. This permits the interpretation that the two hydrocarbon-rich units were deposited and matured in the same basin of Nuna, similar to the Gulf of Mexico during the breakup of Pangea.
Supplemental Material: GMDE: Extracting quantitative information from geologic maps
Authors: Allmendinger R.W.
Published: August 2020

Contains a sample classroom exercise using a map from the Canadian Rocky Mountains that can be done with GMDE.
Primary pulmonary cysticEchinococcusin an immunocompetent patient
Authors: Villalobos Nicholas , Cabanilla Maria Gabriela , Diehl William Paul
Published: August 2020

A 60-year-old man was referred to the interventional pulmonology clinic with a large right-sided intraparenchymal lung mass and a second, smaller lesion in the left lower lobe, accompanied by intermittent haemoptysis, fever, chills, productive cough of white phlegm as well as dizziness and weakness. He had presented previously and was being evaluated for the possibility of malignancy. Investigations had revealed ‘hooklets’ (protoscolices) of hydatid cysts, most likely representing the parasiteEchinococcus. Successful surgical excision of the affected lobe, lung decortication, partial pleurectomy and pneumolysis of the adhesions was performed, along with long-term antiparasitic therapy. The initial differential diagnosis for this patient was challenging and required multimodal investigations. The patient made good recovery and continued to be followed by infectious disease specialists for management of antiparasitic therapy.
Posterior circulation stroke: an easily overlooked complication of catheter ablation of atrial fibrillation
Authors: Nazir Tahir , Sharief Mohiuddin , Farthing James , Ahmed Irfan M
Published: August 2020

Catheter ablation of atrial fibrillation (AF) has established itself as a safe and proven rhythm control strategy for selected patients with AF over the past decade. Thromboembolic complications of catheter ablation are becoming rare in anticoagulated patients with a risk of stroke reported as 0.3%. A particular challenge is posed by clinical presentation due to ischaemic stroke involving the posterior circulation following catheter ablation because of its substantial differences from the carotid territory stroke, making the timely diagnosis and treatment very difficult. It is crucial to keep an index of clinical suspicion in patients presenting with neurological deficits related to vertebrobasilar circulation following ablation. We describe the case of a man who presented with dizziness and palpitations after radiofrequency catheter ablation of AF. He was found to be in AF with a rapid ventricular response. His dizziness was initially attributed to the cardiac dysrhythmia. As his symptoms continued despite heart rate control, he underwent further investigations and was eventually diagnosed with a posterior circulation stroke resulting in left cerebellar infarction. He was treated with antiplatelet therapy and improved significantly over the following few days. We review and present an up-to-date brief literature review on the complications of catheter ablation of AF and describe pathophysiology, clinical features, diagnosis and treatment options for posterior circulation stroke after AF ablation. This case aims to raise awareness among clinicians about posterior circulation stroke after AF ablation.
Acute painless pancreatitis as an unusual presentation of leptospirosis in a low-incidence country
Authors: Schattner Ami , Dubin Ina , Glick Yair , Nissim Elizabeth
Published: August 2020

A healthy, urban-dwelling man presented with lassitude, jaundice without increased liver enzymes or obstructive features on imaging, brief acute kidney injury, leucocytosis with near-normal C reactive protein and markedly increased serum amylase and lipase. Leptospirosis was not considered for 10 days because of the low incidence of the disease in the country, absent animal contact and physicians’ low index of suspicion. Presentation without fever and without the commonly associated abdominal pain, myalgia, headache, thrombocytopaenia or elevated serum creatine kinase added to the diagnostic challenge. Once an infectious cause of acute pancreatitis was contemplated, leptospirosis was immediately sought and diagnosed by PCR of urine and microscopic agglutination test, and he fully recovered on ceftriaxone. Physicians in countries with a low incidence of leptospirosis should be more aware of the possibility of the disease even when several key features such as fever or pain are missing and the patient has a rare infectious acute pancreatitis.
Asystole due to stimulation of the supraorbital nerve: abrupt and potentially fatal presentation of the trigeminocardiac reflex
Authors: Kim Hyunjee , Lim Dong Gun , Kim Jeong Eon
Published: August 2020

We present a case of sudden asystole that was elicited via the trigeminocardiac reflex in a patient undergoing surgery for a frontal sinus fracture. Asystole occurred after mild stimulation of the supraorbital nerve during dissection along the superior orbital rim. Anticholinergics were administered and lidocaine-soaked gauze was applied to the exposed wound. The patient was an athlete and had pre-existing sinus bradycardia. We hypothesise that the severe reflex response was associated with his underlying increased vagal tone. When performing surgery in patients with increased vagal tone, preventative measures to diminish the trigeminocardiac reflex are recommended. Further studies are needed.
Complete response with anti-PD-L1 antibody following progression on anti-PD-1 antibody in advanced non-small cell lung cancer
Authors: Singh Navdeep , Seetharamu Nagashree
Published: August 2020

Immune-checkpoint inhibitors (ICI), specifically inhibitors of programmed death ligand-1 (PD-L1) and receptor (PD-1) are the new standard of care for the treatment of patients with advanced non-small cell lung cancer (NSCLC) in front line setting as monotherapy or along with chemotherapy. Many of these agents are also approved for use in subsequent lines of treatment on progression on platinum doublet chemotherapy. Nivolumab, pembrolizumab and atezolizumab are currently approved ICI for advanced NSCLC. To date, no study has reported efficacy and safety of alternate PD-1/PD-L1 inhibitors in patients with NSCLC who have progressed on one ICI. Here, we report a case of a patient with advanced NSCLC who had a complete response to atezolizumab, following progression of disease on platinum doublet chemotherapy and then, nivolumab monotherapy.
Proximate and socio-economic determinants of under-five mortality in Benin, 2017/2018
Authors: Yaya Sanni , Ahinkorah Bright Opoku , Ameyaw Edward Kwabena , Seidu Abdul-Aziz , Darteh Eugene Kofuor Maafo , Adjei Nicholas Kofi
Published: August 2020

Background

Globally, under-five mortality has declined significantly, but still remains a critical public health problem in sub-Saharan African countries such as Benin. Yet, there is no empirical information in the country using a nationally representative data to explain this phenomenon. The aim of this study was to examine how proximate and socio-economic factors are associated with mortality in under-five children in Benin.

Methods

We analysed data of 5977 under-five children using the 2017 to 2018 Benin Demographic and Health Surveys. Multivariable hierarchical logistic regression modelling technique was applied to investigate the factors associated with under-five mortality. The fit of the models were assessed using variance inflation factor and Pseudo R2. Results were reported as adjusted odds ratios (aORs). All comparisons were considered to be statistically significant at p<0.05.

Results

The study revealed an under-five mortality rate of 96 deaths per 1000 live births in Benin. Regarding the socio-economic determinants, the risk of death was found to be higher in children born in the Plateau region (aOR=3.05; 95% CI: 1.29 to 7.64), in rural areas (aOR=1.45; 95% CI: 1.07 to 1.98) and children with ≥4 birth rank and >2 years of birth interval (aOR=1.52; 95% CI: 1.07 to 2.17). Among the proximate determinants, we found the probability of death to be higher in children whose mothers had no postnatal check-up (PNC) visits after delivery (aOR=1.79; 95% CI: 1.22 to 2.63), but there was no significant association between individual-level/household-level factors and under-five mortality.

Conclusion

This study has established that socio-economic and proximate factors are important determinants of under-five mortality in Benin. Our findings have shown the need to implement both socio-economic and proximate interventions, particularly those related to PNC visits when planning on under-five mortality. To achieve this, a comprehensive, long-term public health interventions, which consider the disparity in the access and utilisation of healthcare services in Benin are key.
Factors associated with going outdoors frequently: a cross-sectional study among Swiss community-dwelling older adults
Authors: Spaltenstein Julia , Bula Christophe , Santos-Eggimann Brigitte , Krief Helene , Seematter-Bagnoud Laurence
Published: August 2020

Objective

This study examines potential risk and protective factors associated with going outdoors frequently among older persons, and whether these factors vary according to physical limitations.

Design

Cross-sectional analysis.

Setting and participants

Community-dwelling participants of the Lausanne cohort Lc65+ in 2016, aged 68–82 years (n=3419).

Methods

Associations between going outdoors frequently and physical limitations, sociodemographic, health, psychological and social variables were examined using logistic regression models. Subgroup analyses were performed according to the severity of physical limitations.

Main outcome measures

‘Going outdoors frequently’ was defined as going out ≥5 days/week and not spending most of the time sitting or lying down.

Results

Three in four (73.9%) participants reported going outdoors frequently. Limitations in climbing stairs (adjusted OR (AdjOR) 0.61, 95% CI 0.47 to 0.80) and walking (AdjOR 0.24, 95% CI 0.18 to 0.31), as well as depressive symptoms (AdjOR 0.58, 95% CI 0.47 to 0.70), dyspnoea (AdjOR 0.60, 95% CI 0.48 to 0.75), age (AdjORolder age group0.73, 95% CI 0.59 to 0.92) and fear of falling (AdjOR 0.75, 95% CI 0.62 to 0.91) reduced the odds of going outdoors frequently. In contrast, living alone (AdjOR 1.30, 95% CI 1.08 to 1.56), reporting a dense (AdjOR 1.57, 95% CI 1.26 to 1.96) and a high-quality (AdjOR 1.28, 95% CI 1.06 to 1.53) social network increased the odds of going outdoors frequently. Among participants with severe limitations, 44.6% still went outdoors frequently. Among this subgroup, a new emotional relationship (AdjOR 2.52, 95% CI 1.18 to 5.38) was associated with going outdoors, whereas cognitive complaints (AdjOR 0.66, 95% CI 0.47 to 0.93), urinary incontinence (AdjOR 0.67, 95% CI 0.46 to 0.97), dyspnea (AdjOR:0.67, 95%CI:0.48-0.93), and depressive symptoms (AdjOR 0.67, 95% CI 0.48 to 0.93) lowered the odds of going outdoors.

Conclusion

Physical limitations are associated with decreased odds of going outdoors frequently. However, social characteristics appear to mitigate this association, even among older persons with severe limitations. Further studies are needed to determine causality and help guide interventions to promote going outdoors as an important component of active ageing.
Design and rationale of DUTCH-AF: a prospective nationwide registry programme and observational study on long-term oral antithrombotic treatment in patients with atrial fibrillation
Authors: Chu Gordon , Seelig Jaap , Trinks-Roerdink Emmy M , van Alem Anouk P , Alings Marco , van den Bemt Bart , Boersma Lucas VA , Brouwer Marc A , Cannegieter Suzanne C , ten Cate Hugo , Kirchhof Charles JHJ , Crijns Harry JGM , van Dijk Ewoud J , Elvan Arif , van Gelder Isabelle C , de Groot Joris R , den Hartog Frank R , de Jong Jonas SSG , de Jong Sylvie , Klok Frederikus A , Lenderink Timo , Luermans Justin G , Meeder Joan G , Pisters Ron , Polak Peter , Rienstra Michiel , Smeets Frans , Tahapary Giovanni JM , Theunissen Luc , Tieleman Robert G , Trines Serge A , van der Voort Pepijn , Geersing Geert-Jan , Rutten Frans H , Hemels Martin EW , Huisman Menno V
Published: August 2020

Introduction

Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials.

Methods and analysis

The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed ‘non-valvular’ AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire.

Ethics and dissemination

This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses.

Trial registration number

Trial NL7467, NTR7706 (https://www.trialregister.nl/trial/7464).
CASNET2: evaluation of an electronic safety netting cancer toolkit for the primary care electronic health record: protocol for a pragmatic stepped-wedge RCT
Authors: Fleming Susannah , Nicholson Brian D , Bhuiya Afsana , de Lusignan Simon , Hirst Yasemin , Hobbs Richard , Perera Rafael , Sherlock Julian , Yonova Ivelina , Bankhead Clare
Published: August 2020

Introduction

Safety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices.

A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web.

Methods and analysis

We will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation.

Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant.

Ethics and dissemination

Ethical approval has been obtained from the North West—Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites.

Trial registration number

ISRCTN15913081; Pre-results.
Decisions to use antibiotics for upper respiratory tract infections across China: a large-scale cross-sectional survey among university students
Authors: Lin Leesa , Fearon Elizabeth , Harbarth Stephan , Wang Xiaomin , Lu Chunling , Zhou Xudong , Hargreaves James R
Published: August 2020

Objectives

To investigate the decision-making process of Chinese university students with respect to antibiotic use for upper respiratory tract infections (URTIs).

Design

A cross-sectional questionnaire study.

Setting

The participants recruited from six universities across all Chinese regions from September to November 2015.

Participants

A total of 2834 university students sampled across six Chinese regions who self-reported experiencing symptoms of URTI within the past month completed the survey.

Outcome measures

The prevalence of decisions for treatment and antibiotic use for URTIs as well as knowledge about antibiotic use were measured by a self-administrated questionnaire. Using regular and multinomial logistic regression a nd adapted health belief model, we identified and measured a number of variables as potential risk factors for antibiotic misuse behaviours in order to explain and predict people’s treatment decisions and antibiotic use including knowledge, perceptions, access to antibiotics and cues to action.

Results

Of the 2834 university students who self-diagnosed a URTI, 947 (33.4%) self-reported having taken antibiotics; among them, 462 (48.8%) used non-prescription antibiotics, which came principally from left-over prescriptions (29.0%) and over-the-counter purchases at retail pharmacies (67.3%). One in four who sought care pressured their doctors for antibiotics; all received them. Those who perceived greater severity of the disease, had access to antibiotics, perceived benefits of using antibiotics (for the common cold: adjusted OR (aOR)=2.55, 95% CI 1.93 to 3.38 or as anti-inflammatory drugs: aOR=1.35, 95% CI 1.12 to 1.63), and were cued to action (eg, seeing presence of fever: aOR=2.05, 95% CI 1.62 to 2.60 or self-diagnosing their current infection as severe: aOR=1.86, 95% CI 1.41 to 2.45), keeping antibiotics at home (aOR=2.27, 95% CI 1.83 to 2.81) and access to over-the-counter antibiotics (aOR=2.00, 95% CI 1.63 to 2.45), were more likely to misuse antibiotics.

Conclusions

Misconceptions of antibiotic efficacy and easy access to antibiotics—with or without a prescription—were associated with antibiotic misuse among Chinese university students, which calls for context-appropriate multifaceted interventions in order to effectively reduce antibiotic misuse.
Rapid cycle system improvement for COVID-19 readiness: integrating deliberate practice, psychological safety and vicarious learning
Authors: Chan Albert Kam Ming , Rudolph Jenny W , Lau Vivian Nga Man , Wong Henry Man Kin , Wong Rosinni Si Ling , Lo Thomas S F , Choi Gordon Y S , Joynt Gavin Matthew
Published: August 2020

Introduction

In the face of a rapidly advancing pandemic with uncertain pathophysiology, pop-up healthcare units, ad hoc teams and unpredictable personal protective equipment supply, it is difficult for healthcare institutions and front-line teams to invent and test robust and safe clinical care pathways for patients and clinicians. Conventional simulation-based education was not designed for the time-pressured and emergent needs of readiness in a pandemic. We used ‘rapid cycle system improvement’ to create a psychologically safe learning oasis in the midst of a pandemic. This oasis provided a context to build staff technical and teamwork capacity and improve clinical workflows simultaneously.

Methods

At the Department of Anaesthesia and Intensive Care in Prince of Wales Hospital, a tertiary institution, in situ simulations were carried out in the operating theatres and intensive care unit (ICU). The translational simulation design leveraged principles of psychological safety, rapid cycle deliberate practice, direct and vicarious learning to ready over 200 staff with 51 sessions and achieve iterative system improvement all within 7 days. Staff evaluations and system improvements were documented postsimulation.

Results/Findings

Staff in both operating theatres and ICU were significantly more comfortable and confident in managing patients with COVID-19 postsimulation. Teamwork, communication and collective ability to manage infectious cases were enhanced. Key system issues were also identified and improved.

Discussion

To develop readiness in the rapidly progressing COVID-19 pandemic, we demonstrated that ‘rapid cycle system improvement’ can efficiently help achieve three intertwined goals: (1) ready staff for new clinical processes, (2) build team competence and confidence and (3) improve workflows and procedures.
Important relation between self-efficacy, sense of coherence, illness perceptions, depression and anxiety in patients with inflammatory bowel disease
Authors: Eindor- Abarbanel Adi , Naftali Timna , Ruhimovich Nahum , Bar-Gil Shitrit Ariella , Sklerovsky-Benjaminov Fabiana , Konikoff Fred , Matalon Shay , Shirin Haim , Milgrom Yael , Ziv-Baran Tomer , Broide Efrat
Published: August 2020

Introduction

Anxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease.

Aims

to investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD.

Patients and methods

Patients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales.

Results

The study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn’s disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014

Conclusions

Anxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients’ psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.
IL-31 induces antitumor immunity in breast carcinoma
Authors: Kan Tal , Feldman Erik , Timaner Michael , Raviv Ziv , Shen-Orr Shai , Aronheim Ami , Shaked Yuval
Published: August 2020

Background

Immunomodulatory agents that induce antitumor immunity have great potential for treatment of cancer. We have previously shown that interleukin (IL)-31, a proinflammatory cytokine from the IL-6 family, acts as an antiangiogenic agent. Here, we characterize the immunomodulatory effect of IL-31 in breast cancer.

Methods

In vivo breast carcinoma models including EMT6 and PyMT cell lines were used to analyze the effect of IL-31 on the composition of various immune cells in the tumor microenvironment using high-throughput flow cytometry. In vitro studies using isolated cytotoxic T cells, CD4+T cells, myeloid-derived suppressor cells (MDSCs) and macrophages were carried out to study IL-31 immunological activity. The generation of recombinant IL-31 bound to IgG backbone was used to test IL-31 therapeutic activity.

Results

The growth rate of IL-31-expressing breast carcinomas is decreased in comparison with control tumors due, in part, to antitumor immunomodulation. Specifically, cytotoxic T cell activity is increased, whereas the levels of CD4+T cells, MDSCs, and tumor-associated macrophages are decreased in IL-31-expressing tumors. These cellular changes are accompanied by a cytokine profile associated with antitumor immunity. In vitro, IL-31 directly inhibits CD4+Th0 cell proliferation, and the expression of Th2 canonical factors GATA3 and IL-4. It also promotes CD8+T cell activation through inhibition of MDSC activity and motility. Clinically, in agreement with the mouse data, alterations in immune cell composition in human breast cancer biopsies were found to correlate with high expression of IL-31 receptor A (IL-31Ra) . Furthermore, high coexpression of IL-31Ra, IL-2 and IL-4 in tumors correlates with increased survival. Lastly, to study the therapeutic potential of IL-31, a recombinant murine IL-31 molecule was fused to IgG via a linker region (IL-31-L-IgG). This IL-31-L-IgG therapy demonstrates antitumor therapeutic activity in a murine breast carcinoma model.

Conclusions

Our findings demonstrate that IL-31 induces antitumor immunity, highlighting its potential utility as a therapeutic immunomodulatory agent.
Rationalizing the pathway to personalized neoadjuvant immunotherapy: the Lombard Street Approach
Authors: Versluis Judith M , Thommen Daniela S , Blank Christian U
Published: August 2020

Neoadjuvant chemo(radio)therapy is part of the established standard of care in cancer treatment; neoadjuvant application of immunotherapy, however, is only performed within recent trials. Combination of programmed cell death protein 1 and cytotoxic T lymphocyte antigen 4 blockade shows promising results with high pathologic response rates in the neoadjuvant setting and a very low relapse rate in the responding patients. In addition, neoadjuvant administration allows direct determination of treatment efficacy within the individual patient, and offers easy access to paired tumor material, both pretherapy and post-therapy, thus facilitates the rational development of new combinations driven by preclinical analyses. Patient-derived human tumor explant systems such as a recently developed human patient-derived tumor fragment platform can provide an additional tool to further rationalize the development of new treatment combinations. We will discuss neoadjuvant immunotherapy as a unique opportunity for rational trial design, the development of immune signatures for non-responding patients to steer clinical trial development, and the use of patient-derived ex vivo models to identify new personalized immunotherapy combinations. In this context, we propose the ‘Lombard Street Approach’, a back and forth approach of characterizing non-responders on neoadjuvant immunotherapy combinations, identifying promising new combinations for this group in the tumor fragment platform, and performing subsequently signature-driven small proof-of-concept combination trials. Repeating this approach with smaller and smaller groups of non-responders will step by step increase the percentage of patients benefiting from neoadjuvant immunotherapy in a rational and fast manner.
Clinical, MRI and histopathological findings in a dog with distemper meningomyelitis
Authors: Destri Alessandra , Sánchez Lluís , Stewart Jennifer , Dennis Ruth
Published: August 2020

A 14‐month‐old female entire German Shepherd dog presented with a five‐day history of acute onset, progressive, non‐ambulatory paraparesis, with lateralisation to the right. The neurolocalisation was to the L4‐S1 spinal cord segments. MRI of the thoracic, lumbar and sacral spinal cord revealed multifocal, ill‐defined, T2‐weighted hyperintense, intramedullary lesions, which were moderately contrast‐enhancing, becoming more defined and ovoid to nodular after injection of gadolinium‐containing contrast medium. The lesions affected both white and grey matter and were lateralised mainly to the right side. PCR tests on blood and cerebrospinal fluid were positive for canine distemper virus (CDV). Despite intensive treatment, the dog developed myoclonus and severe fever and was humanely euthanased. Postmortem examination confirmed the presence of spinal cord lesions consistent with CDV. Distemper rarely presents with clinical signs of myelopathy exclusively and there is a scarcity of description of MRI findings of distemper meningomyelitis in the literature.
Quasi-site-specific prediction for deformation modulus of rock mass
Authors: Ching Jianye , Phoon Kok-Kwang , Ho Yuan-Hsun , Weng Meng-Chia
Published: August 2020

A generic rock mass database consisting of nine parameters is compiled from 225 studies. The nine parameters are the deformation modulus, elastic modulus, dynamic modulus, rock quality designation, rock mass rating, Q-system, geological strength index of a rock mass, as well as intact-rock Young’s modulus and intact-rock uniaxial compressive strength. This generic database, labeled as ROCKMass/9/5876, consists of 5876 rock mass cases. The goal of this paper is to examine how an existing transformation model such as deformation modulus versus rock mass rating can be made more unbiased and more precise for a specific site by combining sparse site data with ROCKMass/9/5876 in a manner sensitive to site-specific differences. The outcome is a quasi-site-specific transformation model. Four methods are studied to construct a quasi-site-specific transformation model for the deformation modulus of a rock mass: probabilistic multiple regression (current state of practice), hybridization method, hierarchical Bayesian model, and similarity method. The results from two case studies in Turkey show that the hierarchical Bayesian model is the most effective.
Functional analysis of the ocnE gene involved in nicotine-degradation pathways in Ochrobactrum intermedium SCUEC4 and its enzymatic properties
Authors: Yu Meng-fei , Xia Zhen-zhen , Yao Jia-cheng , Feng Zhe , Li Ding-hua , Liu Tao , Cheng Guo-jun , He Dong-lan , Li Xiao-hua
Published: August 2020

The SCUEC4 strain of Ochrobactrum intermedium is a newly isolated bacterium that degrades nicotine can use nicotine as the sole carbon source via a series of enzymatic catalytic processes. The mechanisms underlying nicotine degradation in this bacterium and the corresponding functional genes remain unclear. Here, we analyzed the function and biological properties of the ocnE gene involved in the nicotine-degradation pathways in strain SCUEC4. The ocnE gene was cloned by PCR with total DNA of strain SCUEC4 and used to construct the recombinant plasmid pET28a-ocnE. The overexpression of the OcnE protein was detected by SDS–PAGE analysis, and study of the function of this protein was spectrophotometrically carried out by monitoring the changes of 2,5-dihydroxypyridine. Moreover, the effects of temperature, pH, and metal ions on the biological activities of the OcnE protein were analyzed. The optimal conditions for the biological activities of OcnE, a protein of approximately 37.6 kDa, were determined to be 25 °C, pH 7.0, and 25 μmol/L Fe2+, and the suitable storage conditions for the OcnE protein were 0 °C and pH 7.0. In conclusion, the ocnE gene is responsible for the ability of 2,5-dihydroxypyridine dioxygenase. These findings will be beneficial in clarifying the mechanisms of nicotine degradation in O. intermedium SCUEC4.
Soil nitrogen and phosphorus were greater in overlapping areas of fields in Alberta, Saskatchewan, Manitoba, and Ontario
Authors: Crittenden S.J. , Fitzmaurice J. , Lewis M. , Reid K. , Irvine B.
Published: August 2020

A total of 344 soil cores were taken in annually cropped fields of Alberta, Saskatchewan, Manitoba, and Ontario from 2011 to 2013 in areas where the field shapes, or obstacles within fields, required the driving pattern of farm operations to overlap. Soil nitrate-N concentrations in overlapping areas were 60% greater, soil Olsen-P concentrations were 23% greater, and pH was 0.5 units greater at 0–15 cm depth compared with non-overlapping areas, suggesting smaller nutrient use efficiency and potential for greater nutrient loss.