bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in color and reflectance on the surface of asteroid (101955) Bennu
Authors: DellaGiustina D. N. , Burke K. N. , Walsh K. J. , Smith P. H. , Golish D. R. , Bierhaus E. B. , Ballouz R.-L. , Becker T. L. , Campins H. , Tatsumi E. , Yumoto K. , Sugita S. , Deshapriya J. D. Prasanna , Cloutis E. A. , Clark B. E. , Hendrix A. R. , Sen A. , Al Asad M. M. , Daly M. G. , Applin D. M. , Avdellidou C. , Barucci M. A. , Becker K. J. , Bennett C. A. , Bottke W. F. , Brodbeck J. I. , Connolly H. C. , Delbo M. , de Leon J. , Drouet d’Aubigny C. Y. , Edmundson K. L. , Fornasier S. , Hamilton V. E. , Hasselmann P. H. , Hergenrother C. W. , Howell E. S. , Jawin E. R. , Kaplan H. H. , Le Corre L. , Lim L. F. , Li J. Y. , Michel P. , Molaro J. L. , Nolan M. C. , Nolau J. , Pajola M. , Parkinson A. , Popescu M. , Porter N. A. , Rizk B. , Rizos J. L. , Ryan A. J. , Rozitis B. , Shultz N. K. , Simon A. A. , Trang D. , Van Auken R. B. , Wolner C. W. V. , Lauretta D. S.
Published: October 2020

The complex history of Bennu's surface

The near-Earth asteroid (101955) Bennu is a carbon-rich body with a rubble pile structure, formed from debris ejected by an impact on a larger parent asteroid. The Origins, Spectral Interpretation, Resource Identification, Security, Regolith Explorer (OSIRIS-REx) spacecraft is designed to collect a sample of Bennu's surface and return it to Earth. After arriving at Bennu, OSIRIS-REx performed a detailed survey of the asteroid and reconnaissance of potential sites for sample collection. Three papers present results from those mission phases. DellaGiustina
et al.
mapped the optical color and albedo of Bennu's surface and established how they relate to boulders and impact craters, finding complex evolution caused by space weathering processes. Simon
et al.
analyzed near-infrared spectra, finding evidence for organic and carbonate materials that are widely distributed across the surface but are most concentrated on individual boulders. Kaplan
et al.
examined more detailed data collected on the primary sample site, called Nightingale. They identified bright veins with a distinct infrared spectrum in some boulders, which they interpreted as being carbonates formed by aqueous alteration on the parent asteroid. Together, these results constrain Bennu's evolution and provide context for the sample collected in October 2020.

Science
, this issue p.
eabc3660
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eabc3522
, p.
eabc3557
Immunocytokines are a promising immunotherapeutic approach against glioblastoma
Authors: Weiss Tobias , Puca Emanuele , Silginer Manuela , Hemmerle Teresa , Pazahr Shila , Bink Andrea , Weller Michael , Neri Dario , Roth Patrick
Published: October 2020

Immunocytokines display promising antitumor activity in orthotopic mouse models of glioma and patients with glioblastoma.
Inhibition of PfMYST Histone Acetyltransferase Activity Blocks Plasmodium falciparum Growth and Survival
Authors: Sen Utsav , Nayak Akshaykumar , Khurana Juhi , Sharma Deepu , Gupta Ashish
Published: October 2020

One of the major barriers in the prevention and control of malaria programs worldwide is the growing emergence of multidrug resistance in
Plasmodium
parasites, and this necessitates continued efforts to discover and develop effective drug molecules targeting novel proteins essential for parasite survival. In recent years, epigenetic regulators have evolved as an attractive drug target option owing to their crucial role in survival and development of
Plasmodium
at different stages of its life cycle.
Comparison of Proteomic Responses as Global Approach to Antibiotic Mechanism of Action Elucidation
Authors: Senges Christoph H. R. , Stepanek Jennifer J. , Wenzel Michaela , Raatschen Nadja , Ay Ümran , Märtens Yvonne , Prochnow Pascal , Vázquez Hernández Melissa , Yayci Abdulkadir , Schubert Britta , Janzing Niklas B. M. , Warmuth Helen L. , Kozik Martin , Bongard Jens , Alumasa John N. , Albada Bauke , Penkova Maya , Lukežič Tadeja , Sorto Nohemy A. , Lorenz Nicole , Miller Reece G. , Zhu Bingyao , Benda Martin , Stülke Jörg , Schäkermann Sina , Leichert Lars I. , Scheinpflug Kathi , Brötz-Oesterhelt Heike , Hertweck Christian , Shaw Jared T. , Petković Hrvoje , Brunel Jean M. , Keiler Kenneth C. , Metzler-Nolte Nils , Bandow Julia E.
Published: October 2020

New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of
Bacillus subtilis
covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis.
The LysR-Type Transcriptional Regulator CrgA Negatively Regulates the Flagellar Master Regulator
flhDC
in Ralstonia solanacearum GMI1000
Authors: Fan Xiaojing , Zhao Zhiwen , Sun Tingyan , Rou Wei , Gui Caiying , Saleem Tahira , Zhao Xuxu , Xu Xianyuan , Zhuo Tao , Hu Xun , Zou Huasong
Published: October 2020

Ralstonia solanacearum
is a widely distributed soilborne plant pathogen that causes bacterial wilt disease on diverse plant species. Motility is a critical virulence attribute of
R. solanacearum
because it allows this pathogen to efficiently invade and colonize host plants. In
R. solanacearum
, motility-defective strains are markedly affected in pathogenicity, which is coregulated with multiple virulence factors. In this study, we identified a new LysR-type transcriptional regulator (LTTR), CrgA, that negatively regulates motility. The mutation of the corresponding gene leads to the precocious appearance of wilt symptoms on tomato plants when the pathogen is introduced using soil-soaking inoculation. This study indicates that the regulation of
R. solanacearum
motility is more complex than previously thought and enhances our understanding of flagellum regulation in
R. solanacearum
.
Clustered Lysine Residues of the Canine Distemper Virus Matrix Protein Regulate Membrane Association and Budding Activity
Authors: Kadzioch Nicole P. , Gast Matthieu , Origgi Francesco , Plattet Philippe
Published: October 2020

Although vaccines against some morbilliviruses exist, infections still occur, which can result in dramatic brain disease or fatal outcome. Postexposure prophylaxis with antivirals would support global vaccination campaigns. Unfortunately, there is no efficient antiviral drug currently approved. The matrix (M) protein of morbilliviruses coordinates viral assembly and egress through interaction with multiple cellular and viral components. However, molecular mechanisms supporting these functions remain poorly understood, which preclude the rationale design of inhibitors. Here, to investigate potential interactions between canine distemper virus (CDV) M and the plasma membrane (PM), we combined structure-guided mutagenesis of selected surface-exposed lysine residues with biochemical, cellular, and virological assays. We identified several lysines clustering in a basic patch microdomain of the CDV M C-terminal domain, which contributed to PM association and budding activity. Our findings provide novel mechanistic information of how morbilliviruses assemble and egress from infected cells, thereby delivering bases for future antiviral drug development.
First clinical report of aspiration through a novel 0.088-inch catheter positioned in the M1 middle cerebral artery for ELVO thrombectomy
Authors: Gershon Blake S , Bageac Devin V , Shigematsu Tomoyoshi , Majidi Shahram , De Leacy Reade
Published: October 2020

Two patients, separated by 1 year, underwent mechanical thrombectomy using next generation, highly navigable 0.088-inch large bore catheters, which were navigated to and aspirated within the M1 middle cerebral artery segment. Case 1 demonstrates the first reported clinical application of this technique used in conjunction with stent retriever and direct aspiration through an intermediate catheter, resulting in modified thrombolysis in cerebral infarction (mTICI) score 3 recanalisation, and a 90-day modified Rankin Score of 1. In case 2, direct on-clot aspiration was applied through a 0.088-inch guide catheter in the left M1 segment, resulting in mTICI score 3 recanalisation and a National Institutes of Health Stroke Scale score of 1 at discharge. There was no evidence of untoward events in either case. Advancement of a 0.088-inch catheter into the M1 segment offers potential benefits to thrombectomy by improving device-thrombus interaction, inducing local flow arrest and protecting proximal vessels from embolus to new territories.
First trimester cerebral appearance in the presence of closed spina bifida with myelomeningocele, part of the oeis complex
Authors: Ungureanu Delia Roxana , Zorila Lucian George , Capitanescu Razvan Grigoras , Iliescu Dominic Gabriel
Published: October 2020

Our communication presents a prenatally detected case with severe spinal defect detected in the first trimester of pregnancy, accompanied by a large skin-covered myelomeningocele but normal cranio-cerebral structural appearance.

These findings suggest that in the first trimester, the extent of the spinal defect, the cerebrospinal fluid leakage to a large, but skin-covered, meningocele and fixation of the spinal cord at the lesion are not sufficient to determine downward hindbrain displacement and the development of secondary signs for open spina bifida.

Therefore, we suggest a careful evaluation of the fetal cerebral features if a meningocele is detected. The presence of the skin covering the lesion may not be evident in the first trimester, but the absence of intracranial open spina bifida markers may indicate a ‘closed’ spinal defect, which generally associates a good neurological outcome. Also, studies aimed to investigate the accuracy of the intracranial features for open spina bifida detection should consider the possibility of ‘closed’ myelomeningoceles to avoid incorrect correlations.
Why does activated partial thromboplastin time prolongation occur in severe fever with thrombocytopenia syndrome?
Authors: Mizoe Atsushi , Sakaue Junya , Takahara Noriko
Published: October 2020

Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with SFTS virus and this mortality rate is 16.2% to 30%. An 85-year-old male patient presented to the emergency department of the hospital with primary complaints of fever and consciousness disturbance. Haemophagocytic syndrome and prolonged activated partial thromboplastin time (APTT) without associated prolonged prothrombin time were observed, suggesting SFTS, which was eventually diagnosed. APTT-only prolongation has been reported previously with SFTS, but the mechanism is unknown. The absence of coagulation factors was determined by a cross-mixing study. In addition, examination of intrinsic coagulation factors showed reduced factor XI activity. These results suggest that factor XI is causally related to APTT-only prolongation in SFTS.
Metastatic pulmonary dissemination as differential diagnosis of COVID-19 disease
Authors: Perdigón Martinelli Cristel , Morell Carlos , González Carolina , Nova-Lozano Cristina
Published: October 2020

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks’ duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing’s sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.
Effect of school closures on mortality from coronavirus disease 2019: old and new predictions
Authors: Rice Ken , Wynne Ben , Martin Victoria , Ackland Graeme J
Published: October 2020

Objective

To replicate and analyse the information available to UK policymakers when the lockdown decision was taken in March 2020 in the United Kingdom.

Design

Independent calculations using the CovidSim code, which implements Imperial College London’s individual based model, with data available in March 2020 applied to the coronavirus disease 2019 (covid-19) epidemic.

Setting

Simulations considering the spread of covid-19 in Great Britain and Northern Ireland.

Population

About 70 million simulated people matched as closely as possible to actual UK demographics, geography, and social behaviours.

Main outcome measures

Replication of summary data on the covid-19 epidemic reported to the UK government Scientific Advisory Group for Emergencies (SAGE), and a detailed study of unpublished results, especially the effect of school closures.

Results

The CovidSim model would have produced a good forecast of the subsequent data if initialised with a reproduction number of about 3.5 for covid-19. The model predicted that school closures and isolation of younger people would increase the total number of deaths, albeit postponed to a second and subsequent waves. The findings of this study suggest that prompt interventions were shown to be highly effective at reducing peak demand for intensive care unit (ICU) beds but also prolong the epidemic, in some cases resulting in more deaths long term. This happens because covid-19 related mortality is highly skewed towards older age groups. In the absence of an effective vaccination programme, none of the proposed mitigation strategies in the UK would reduce the predicted total number of deaths below 200 000.

Conclusions

It was predicted in March 2020 that in response to covid-19 a broad lockdown, as opposed to a focus on shielding the most vulnerable members of society, would reduce immediate demand for ICU beds at the cost of more deaths long term. The optimal strategy for saving lives in a covid-19 epidemic is different from that anticipated for an influenza epidemic with a different mortality age profile.
Can extranodal tumour deposits be diagnosed on MRI? Protocol for a multicentre clinical trial (the COMET trial)
Authors: Lord Amy C , Moran Brendan , Abulafi Muti , Rasheed Shahnawaz , Nagtegaal Iris D , Terlizzo Monica , Brown Gina
Published: October 2020

Introduction

Tumour deposits (TDs) are a poor prognostic marker when seen on pathology, and are worse than lymph node metastases (LNMs). They are now being reported on MRI as discontinuous nodules of extramural venous invasion but this diagnosis has not been validated and it is unclear how it correlates with the diagnosis of TDs on pathology.

Methods and analysis

This is a prospective interventional clinical trial which aims to directly map the location of TDs on MRI and correlate what is seen on MRI with the pathology findings at each location. All patients with rectal cancer undergoing resectional surgery are eligible (including those undergoing preoperative therapy). The primary outcome is the prevalence of TDs seen on pathology. Secondary outcomes are to assess radiological and pathological interobserver agreement, assess the effect of TDs on prognosis and carry out exploratory work looking at differences between TDs and LNMs. The estimated sample size is 100 to detect a twofold increase in the pathological diagnosis of TD when MRI mapping is used.

Ethics and dissemination

Ethical approval has been granted from the South Central—Hampshire B Research and Ethics Committee (IRAS 217627). The study will be carried out under standard operative procedures within the Royal Marsden Hospital.

Trial registration number

NCT03303547.
Determinants of citation in the literature on diesel exhaust exposure and lung cancer: a citation analysis
Authors: Duyx Bram , Urlings Miriam J E , Swaen Gerard M H , Bouter Lex M , Zeegers Maurice P
Published: October 2020

Objectives

Epidemiological research on the association between diesel exhaust exposure and lung cancer risk has some methodological challenges that give rise to different conclusions and intense debates. This raises the question about the role of selective citation and of citation bias in particular. Our aim was to investigate the occurrence and prevalence of selective citation in this field.

Design

Citation analysis.

Setting

Web of Science Core Collection.

Participants

We identified 96 publications in this network, with 4317 potential citations. For each publication, we extracted characteristics such as study conclusion and funding source. Some of these characteristics are related to the study content: study design, sample size, method of diesel exposure assessment, type of diesel technology under investigation, and whether smoking had been adjusted for.

Primary and secondary outcome measures

Whether a citation occurs or not, measured and analysed according to the preregistered protocol. Exploratively we analysed the association between funding source and study conclusion.

Results

Methodological content of a study was clearly related to citation, studies using more sophisticated methods were more likely to be cited. There was some evidence for citation bias: supportive publications had a higher chance of being cited than non-supportive ones, but after adjustment for study quality, this effect decreased substantially (adjusted OR 1.3, 95% CI 1.0 to 1.7). Explorative analyses indicated that three quarters of non-profit funded publications had a supportive study conclusion against only one quarter of the industry-funded publications.

Conclusions

There is evidence for selective citation within this field, but the evidence for citation bias was weak. It seems that factors related to the methodology had more impact on citation than the conclusion of a study. Interestingly, publications that were funded by industry were more skeptical about a causal relationship between diesel exhaust and lung cancer compared to non-profit-funded publications.
Do measures of physical function enhance the prediction of persistent pain and disability following a whiplash injury? Protocol for a prospective observational study in Spain
Authors: Alalawi Ahmed , Luque-Suarez Alejandro , Fernandez-Sanchez Manuel , Gallina Alessio , Evans David , Falla Deborah
Published: October 2020

Introduction

Not all factors that predict persistent pain and disability following whiplash injury are known. In particular, few physical factors, such as changes in movement and muscle behaviour, have been investigated. The aim of this study is to identify predictive factors that are associated with the development of persistent pain and disability following a whiplash injury by combining contemporary measures of physical function together with established psychological and pain-related predictive factors.

Methods and analysis

A prospective observational study will recruit 150 consecutive eligible patients experiencing whiplash-related symptoms, admitted to a private physiotherapy clinic in Spain within 15 days of their whiplash injury. Poor outcome will be measured using the Neck Disability Index (NDI), defined as an NDI score of 30% or greater at 6 months post injury. Candidate predictors, including demographic characteristics, injury characteristics, pain characteristics, self-reported psychosocial factors and physical factors, will be collected at baseline (within 15 days of inception). Regression analyses will be performed to identify factors that are associated with persistent neck pain and disability over the study period.

Ethics and dissemination

The project has been approved by the Ethics Committee of the province of Malaga, Spain (#30052019). The results of this study will be published in peer-reviewed journals.
Comparison of PGS2.0 versus conventional embryo morphology evaluation for patients with recurrent pregnancy loss: a study protocol for a multicentre randomised trial
Authors: Lei Caixia , Sui Yilun , Ye Jiangfeng , Lu Yao , Xi Ji , Sun Yun , Jin Li , Sun Xiaoxi
Published: October 2020

Introduction

Pregnancy loss (PL) is an adverse life event, and there is no proven effective treatment for recurrent PL (RPL). Preimplantation genetic screening (PGS) can be performed to reduce the risks of PL; however, there is still no solid scientific evidence that PGS improves outcomes for couples experiencing RPL. Comprehensive chromosome screening (PGS2.0) has become a routine practice in in vitro fertilisation (IVF) clinics. Previous studies based on PGS1.0 with a focus on RPL couples where the female is of advanced maternal age have reported contradictory results. Hence, a multicentre randomised trial is needed to provide evidence for the clinical benefits of PGS2.0 treatment for RPL couples.

Methods and analysis

Overall, 268 RPL couples undergoing IVF cycles will be enrolled. Couples will be randomised according to a unique grouping number generated by a random digital software into (1) PGS2.0 group and (2) non-PGS (conventional embryo morphology evaluation) group. This study aims to investigate whether the live birth rate (LBR) per initiated cycle after PGS2.0 is superior to the LBR per initiated cycle after conventional embryo evaluation (non-PGS group). Live birth will be defined as a live baby born after a gestation period of >28 weeks, with a birth weight of more than 1000 g. A multivariate logistic regression model will be used to adjust for confounding factors.

Ethics and dissemination

Ethical approval has been granted by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University and the participating hospitals. Written informed consent will be obtained from each couple before any study procedure is performed. Data from this study will be stored in the Research Electronic Data Capture. The results of this trial will be presented and published via peer-reviewed publications and presentations at international conferences.

Trial registration number

NCT03214185; Pre-results.
Are there ethnic and religious variations in uptake of bowel cancer screening? A retrospective cohort study among 1.7 million people in Scotland
Authors: Campbell Christine , Douglas Anne , Williams Linda , Cezard Geneviève , Brewster David H , Buchanan Duncan , Robb Kathryn , Stanners Greig , Weller David , Steele Robert JC , Steiner Markus , Bhopal Raj
Published: October 2020

Objective

Cancer screening should be equitably accessed by all populations. Uptake of colorectal cancer screening was examined using the Scottish Health and Ethnicity Linkage Study that links the Scottish Census 2001 to health data by individual-level self-reported ethnicity and religion.

Setting

Data on 1.7 million individuals in two rounds of the Scottish Bowel Cancer Screening Programme (2007–2013) were linked to the 2001 Census using the Scottish Community Health Index number.

Main outcome measure

Uptake of colorectal cancer screening, reported as age-adjusted risk ratios (RRs) by ethnic group and religion were calculated for men and women with 95% CI.

Results

In the first, incidence screening round, compared with white Scottish men, Other White British (RR 109.6, 95% CI 108.8 to 110.3) and Chinese (107.2, 95% CI 102.8 to 111.8) men had higher uptake. In contrast, men of all South Asian groups had lower uptake (Indian RR 80.5, 95% CI 76.1 to 85.1; Pakistani RR 65.9, 95% CI 62.7 to 69.3; Bangladeshi RR 76.6, 95% CI 63.9 to 91.9; Other South Asian RR 88.6, 95% CI 81.8 to 96.1). Comparable patterns were seen among women in all ethnic groups, for example, Pakistani (RR 55.5, 95% CI 52.5 to 58.8). Variation in uptake was also observed by religion, with lower rates among Hindu (RR (95%CI): 78.4 (71.8 to 85.6)), Muslim (69.5 (66.7 to 72.3)) and Sikh (73.4 (67.1 to 80.3)) men compared with the reference population (Church of Scotland), with similar variation among women: lower rates were also seen among those who reported being Jewish, Roman Catholic or with no religion.

Conclusions

There are important variations in uptake of bowel cancer screening by ethnic group and religion in Scotland, for both sexes, that require further research and targeted interventions.
Efficacy and mid/long-term survivorship of mobile-bearing unicompartmental knee arthroplasty for medial compartment knee osteoarthritis combined patellofemoral joint arthritis: a prospective cohort study protocol
Authors: Cheng Jingbo , Feng Mingli , Cao Guanglei , Lu Shibao
Published: October 2020

Introduction

Unicompartmental knee arthroplasty (UKA) is one of the most effective surgical procedures for treating isolated medial compartment knee osteoarthritis. However, previous studies have regarded patellofemoral osteoarthritis as a contraindication for UKA. In contrast, most current research shows that damage to the articular cartilage of the patellofemoral joint, even to the extent of full-thickness cartilage loss, has no influence on the outcome of UKA.

Methods and analysis

Study settings: This study is a prospective cohort study that will compare the Forgotten Joint Score and Lonner patellofemoral joint score of patients who have undergone UKA; the patients will be divided into two groups (with and without patellofemoral joint osteoarthritis (PFJOA)). Primary objective: Long-term follow-up will be used to evaluate the effect of the operation on the above-mentioned scores in both the groups. Secondary objective: We will divide the patients from the with PFJOA group into three subgroups according to the localisation of patellofemoral cartilage lesions (medial zone, lateral zone and central zone). We aim to compare knee joint scores among these groups and clarify the impact of different wear sites on clinical efficacy. We will use CT to explore the potential mechanism through which UKA affects patellofemoral joint-related parameters (lateral patellar tilt, lateral patellar shift and tibia tuberosity-trochlear groove distance). We will also record mid-term/long-term post-surgery complications.

Ethics and dissemination

This study’s protocol is in accordance with the Declaration of Helsinki. This study was approved by the Ethics Committee of Xuanwu Hospital. The results of this study will be disseminated in international peer-reviewed journals.

Trial registration number

ChiCTR2000030310.
Protocol for Project Fizzyo, an analytic longitudinal observational cohort study of physiotherapy for children and young people with cystic fibrosis, with interrupted time-series design
Authors: Raywood Emma , Douglas Helen , Kapoor Kunal , Filipow Nicole , Murray Nicky , O'Connor Rachel , Stott Lee , Saul Greg , Kuzhagaliyev Tim , Davies Gwyneth , Liakhovich Olga , Van Schaik Tempest , Furtuna Bianca , Booth John , Shannon Harriet , Bryon Mandy , Main Eleanor
Published: October 2020

Introduction

Daily physiotherapy is believed to mitigate the progression of cystic fibrosis (CF) lung disease. However, physiotherapy airway clearance techniques (ACTs) are burdensome and the evidence guiding practice remains weak. This paper describes the protocol for Project Fizzyo, which uses innovative technology and analysis methods to remotely capture longitudinal daily data from physiotherapy treatments to measure adherence and prospectively evaluate associations with clinical outcomes.

Methods and analysis

A cohort of 145 children and young people with CF aged 6–16 years were recruited. Each participant will record their usual physiotherapy sessions daily for 16 months, using remote monitoring sensors: (1) a bespoke ACT sensor, inserted into their usual ACT device and (2) a Fitbit Alta HR activity tracker. Real-time breath pressure during ACTs, and heart rate and daily step counts (Fitbit) are synced using specific software applications. An interrupted time-series design will facilitate evaluation of ACT interventions (feedback and ACT-driven gaming). Baseline, mid and endpoint assessments of spirometry, exercise capacity and quality of life and longitudinal clinical record data will also be collected.

This large dataset will be analysed in R using big data analytics approaches. Distinct ACT and physical activity adherence profiles will be identified, using cluster analysis to define groups of individuals based on measured characteristics and any relationships to clinical profiles assessed. Changes in adherence to physiotherapy over time or in relation to ACT interventions will be quantified and evaluated in relation to clinical outcomes.

Ethics and dissemination

Ethical approval for this study (IRAS: 228625) was granted by the London-Brighton and Sussex NREC (18/LO/1038). Findings will be disseminated via peer-reviewed publications, at conferences and via CF clinical networks. The statistical code will be published in the Fizzyo GitHub repository and the dataset stored in the Great Ormond Street Hospital Digital Research Environment.

Trial registration number

ISRCTN51624752; Pre-results.
Reduced survival after upper gastrointestinal bleed endoscopy in the COVID-19 era is a secondary effect of the response to the global pandemic: a retrospective cohort study
Authors: Tavabie Oliver D , Clough Jennie N , Blackwell Jonathan , Bashyam Maria , Martin Harry , Soubieres Anet , Direkze Natalie , Graham David , Groves Christopher , Preston Sean L , DeMartino Sabina , Gill Upkar S , Hayee Bu'Hussain , Joshi Deepak
Published: October 2020

Objective

The COVID-19 pandemic has placed increased strain on healthcare systems worldwide with enormous reorganisation undertaken to support ‘COVID-centric’ services. Non-COVID-19 admissions reduced secondary to public health measures to halt viral transmission. We aimed to understand the impact of the response to COVID-19 on the outcomes of upper gastrointestinal (UGI) bleeds.

Design/methods

A retrospective observational multicentre study comparing outcomes following endoscopy for UGI bleeds from 24 March 2020 to 20 April 2020 to the corresponding dates in 2019. The primary outcome was in-hospital survival at 30 days with secondary outcomes of major rebleeding within 30 days postprocedure and intervention at the time of endoscopy.

Results

224 endoscopies for 203 patients with UGI bleeds were included within this study. 19 patients were diagnosed with COVID-19. There was a 44.4% reduction in the number of procedures performed between 2019 and 2020. Endoscopies performed for UGI bleeds in the COVID-19 era were associated with an adjusted reduced 30-day survival (OR 0.25, 95% CI 0.08–0.67). There was no increased risk of major rebleeding or interventions during this era. Patients with COVID-19 did not have reduced survival or increased complication rates.

Conclusion

Endoscopy for UGI bleeds in the COVID-19 era is associated with reduced survival. No clear cause has been identified but we suspect that this is a secondary effect of the response to the COVID-19 pandemic. Urgent work is required to encourage the public to seek medical help if required and to optimise patient pathways to ensure that the best possible care is provided.
Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population
Authors: So Jimmy Bok Yan , Kapoor Ritika , Zhu Feng , Koh Calvin , Zhou Lihan , Zou Ruiyang , Tang Yew Chung , Goo Patrick C K , Rha Sun Young , Chung Hyun Cheol , Yoong Joanne , Yap Celestial T , Rao Jaideepraj , Chia Chung-King , Tsao Stephen , Shabbir Asim , Lee Jonathan , Lam Kong-Peng , Hartman Mikael , Yong Wei Peng , Too Heng-Phon , Yeoh Khay-Guan
Published: October 2020

Objective

An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population.

Design

We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea. Biomarker discovery and verification phases were done through comprehensive serum miRNA profiling and multivariant analysis of 578 miRNA candidates in retrospective cohorts of 682 subjects. A clinical assay was developed and validated in a prospective cohort of 4566 symptomatic subjects who underwent endoscopy. Assay performance was confirmed with histological diagnosis and compared withHelicobacter pylori(HP) serology, serum pepsinogens (PGs), ‘ABC’ method, carcinoembryonic antigen (CEA) and cancer antigen 19–9 (CA19-9). Cost-effectiveness was analysed using a Markov decision model.

Results

We developed a clinical assay for detection of gastric cancer based on a 12-miRNA biomarker panel. The 12-miRNA panel had area under the curve (AUC)=0.93 (95% CI 0.90 to 0.95) and AUC=0.92 (95% CI 0.88 to 0.96) in the discovery and verification cohorts, respectively. In the prospective study, overall sensitivity was 87.0% (95% CI 79.4% to 92.5%) at specificity of 68.4% (95% CI 67.0% to 69.8%). AUC was 0.848 (95% CI 0.81 to 0.88), higher than HP serology (0.635), PG 1/2 ratio (0.641), PG index (0.576), ABC method (0.647), CEA (0.576) and CA19-9 (0.595). The number needed to screen is 489 annually. It is cost-effective for mass screening relative to current practice (incremental cost-effectiveness ratio=US$44 531/quality-of-life year).

Conclusion

We developed and validated a serum 12-miRNA biomarker assay, which may be a cost-effective risk assessment for gastric cancer.

Trial registration number

This study is registered with ClinicalTrials.gov (Registration number:NCT04329299).
Socioeconomic inequality in the risk of intentional injuries among adolescents: a cross-sectional analysis of 89 countries
Authors: Probst Charlotte , Kilian Carolin , Rehm Jürgen , Carvalho Andre F , Koyanagi Ai , Lange Shannon
Published: October 2020

Introduction

In 2015, the elimination of hunger worldwide by 2030 was declared by the United Nations as a Sustainable Development Goal. However, food insecurity remains pervasive, contributing to socioeconomic health inequalities. The overall objective was to investigate the relationship between food insecurity and intentional injuries among adolescents.

Methods

Individual-level data from the Global School-based Student Health Survey from 89 countries were used (370 719 adolescents, aged 12–17 years). Multilevel logistic regressions were used to examine the sex-specific association between the level of food insecurity (none, medium and high) and intentional injuries (interpersonal violence and suicide attempts), accounting for the clustering of observations within surveys. Random-effects meta-analyses were used to analyse dose–response relationships.

Results

Medium and high food insecurity were associated with increased odds of reporting an injury from interpersonal violence among both sexes. A positive dose–response relationship was found, where each level increase in food insecurity was associated with a 30% increase in the odds of an injury due to interpersonal violence among boys (1.30; 95% CI 1.26 to 1.34) and a 50% increase among girls (1.53; 95% CI 1.46–1.62). The odds for suicide attempts increased by 30% for both sexes with each level increase in food insecurity (boys: 1.29; 95% CI 1.25–1.32; girls: 1.29; 95% CI 1.25–1.32).

Discussion

The findings indicate that socioeconomic inequalities exist in the risk of intentional injuries among adolescents. Although additional studies are needed to establish causality, the present study suggests that the amelioration of food insecurity could have implications beyond the prevention of its direct consequences.
2,5-dimethylcelecoxib improves immune microenvironment of hepatocellular carcinoma by promoting ubiquitination of HBx-induced PD-L1
Authors: Chen Zhanfei , Chen Yiyin , Peng Lirong , Wang Xiaoqian , Tang Nanhong
Published: October 2020

Background

2,5-dimethylcelecoxib (DMC) is a targeted inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1), a key enzyme in the PGE2 synthesis pathway of inflammatory mediators. Previous studies have confirmed that DMC can inhibit the growth of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, it is not known whether DMC is involved in the changes of tumor immune microenvironment.

Methods

In this study, we explored the effects of DMC on HBV-related HCC immune microenvironment, and deeply analyzed its unique effect and mechanism on programmed death receptor 1 (PD-1)/and its ligand 1 (PD-L1) pathway.

Results

Clinical hepatoma tissues detection showed that compared with non-virus-related HCC, the level of CD8 of HBV-related HCC was significantly lower, while the levels of PD-L1 and CD163 were higher. In vivo experiments indicated that DMC could increase the level of tumor infiltrating CD8+ T cells in hepatitis B virus X (HBx) (+) hepatoma cells implanted mouse models, and inhibit the expression of PD-L1 and CD163 in tumor tissues. DMC combined with atezolizumab had more significant antitumor effect and stronger blocking effect on PD-1/PD-L1 pathway. Mechanism studies have shown that DMC can promote ubiquitin degradation of HBx-induced PD-L1 protein in HCC cells by activating adenosine 5′-monophosphate-activated protein kinase pathway. Further experiments confirmed that this process was mainly mediated by E3 ligase RBX1.

Conclusions

Our results uncover a role for DMC in promoting HBV-related HCC immune microenvironment, which not only enrich the relationship between inflammatory factors (mPGES-1/PGE2 pathway) and immunosuppression (PD-L1), but also provide an important strategic reference for multitarget or combined immunotherapy of HBV-related HCC.
Analysis of the molecular nature associated with microsatellite status in colon cancer identifies clinical implications for immunotherapy
Authors: Bao Xuanwen , Zhang Hangyu , Wu Wei , Cheng Shaobing , Dai Xiaomeng , Zhu Xudong , Fu Qihan , Tong Zhou , Liu Lulu , Zheng Yi , Zhao Peng , Fang Weijia , Liu Fanglong
Published: October 2020

Background

Microsatellite instability in colon cancer implies favorable therapeutic outcomes after checkpoint blockade immunotherapy. However, the molecular nature of microsatellite instability is not well elucidated.

Methods

We examined the immune microenvironment of colon cancer using assessments of the bulk transcriptome and the single-cell transcriptome focusing on molecular nature of microsatellite stability (MSS) and microsatellite instability (MSI) in colorectal cancer from a public database. The association of the mutation pattern and microsatellite status was analyzed by a random forest algorithm in The Cancer Genome Atlas (TCGA) and validated by our in-house dataset (39 tumor mutational burden (TMB)-low MSS colon cancer, 10 TMB-high MSS colon cancer, 15 MSI colon cancer). A prognostic model was constructed to predict the survival potential and stratify microsatellite status by a neural network.

Results

Despite the hostile CD8+cytotoxic T lymphocyte (CTL)/Th1 microenvironment in MSI colon cancer, a high percentage of exhausted CD8+T cells and upregulated expression of immune checkpoints were identified in MSI colon cancer at the single-cell level, indicating the potential neutralizing effect of cytotoxic T-cell activity by exhausted T-cell status. A more homogeneous highly expressed pattern of PD1 was observed in CD8+T cells from MSI colon cancer; however, a small subgroup of CD8+T cells with high expression of checkpoint molecules was identified in MSS patients. A random forest algorithm predicted important mutations that were associated with MSI status in the TCGA colon cancer cohort, and our in-house cohort validated higher frequencies ofBRAF,ARID1A,RNF43, andKM2Bmutations in MSI colon cancer. A robust microsatellite status–related gene signature was built to predict the prognosis and differentiate between MSI and MSS tumors. A neural network using the expression profile of the microsatellite status–related gene signature was constructed. A receiver operating characteristic curve was used to evaluate the accuracy rate of neural network, reaching 100%.

Conclusion

Our analysis unraveled the difference in the molecular nature and genomic variance in MSI and MSS colon cancer. The microsatellite status–related gene signature is better at predicting the prognosis of patients with colon cancer and response to the combination of immune checkpoint inhibitor–based immunotherapy and anti-VEGF therapy.
Transition to virtual appointments for interventional neuroradiology due to the COVID-19 pandemic: a survey of satisfaction
Authors: Lun Ronda , Walker Gregory , Daham Zeinab , Ramsay Tim , Portela de Oliveira Eduardo , Kassab Mohammed , Fahed Robert , Quateen Aiman , Lesiuk Howard , P dos Santos Marlise , Drake Brian
Published: October 2020

Background

The COVID-19 pandemic has changed the way medicine is practiced, including the implementation of virtual care in many specialties. In the field of interventional neuroradiology (INR), virtual clinics are an uncommon practice with minimal literature to support its use. Our objective was to report prospective, single-centre data regarding patient and physician experience with virtual INR clinics for routine follow-up appointments.

Methods

We surveyed all patients that participated in a virtual INR clinic follow-up appointment at our hospital over a 3 month period. Information gathered included length of appointment delays (ie, wait times), length of appointment times, overall satisfaction, and perceived safety metrics. A survey was also sent out to all physicians who participated in virtual clinics with similar questions.

Results

118/122 patients and 6/6 physicians completed the survey. Wait times before previous in-person appointments were perceived to be much longer than virtual appointments, whereas in-person appointment times were longer. 112/118 (94.9%) patients and 4/6 (67%) physicians reported general satisfaction with their virtual clinic experience. There were 8/118 patients who felt their conditions could not be safely assessed virtually, compared with 1/6 (17%) physicians. Lastly, 72.2% of patients reported that they would prefer virtual or telephone visits in the future for non-urgent follow-up, and 5/6 (83%) of physicians reported the same.

Conclusion

Virtual INR clinics are more efficient and are preferred among patients and physicians for non-urgent follow-up appointments. Our study demonstrates the feasibility of a virtual platform for INR care, which could be sustainable for future practice.
COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment
Authors: Parasher Anant
Published: October 2020

Background

The severe acute respiratory syndrome (SARS) coronavirus-2 is a novel coronavirus belonging to the family Coronaviridae and is now known to be responsible for the outbreak of a series of recent acute atypical respiratory infections originating in Wuhan, China. The disease caused by this virus, termed coronavirus disease 19 or simply COVID-19, has rapidly spread throughout the world at an alarming pace and has been declared a pandemic by the WHO on March 11, 2020. In this review, an update on the pathophysiology, clinical presentation and the most recent management strategies for COVID-19 has been described.

Materials and Methods

A search was conducted for literature and various articles/case reports from 1997 to 2020 in PUBMED/MEDLINE for the keywords coronavirus, SARS, Middle East respiratory syndrome and mRNA virus.

Results and Conclusions

COVID-19 has now spread globally with increasing morbidity and mortality among all populations. In the absence of a proper and effective antibody test, the diagnosis is presently based on a reverse-transcription PCR of nasopharyngeal and oropharyngeal swab samples. The clinical spectrum of the disease presents in the form of a mild, moderate or severe illness. Most patients are either asymptomatic carriers who despite being without symptoms have the potential to be infectious to others coming in close contact, or have a mild influenza-like illness which cannot be differentiated from a simple upper respiratory tract infection. Moderate and severe cases require hospitalisation as well as intensive therapy which includes non-invasive as well as invasive ventilation, along with antipyretics, antivirals, antibiotics and steroids. Complicated cases may require treatment by immunomodulatory drugs and plasma exchange therapy. The search for an effective vaccine for COVID-19 is presently in full swing, with pharmaceutical corporations having started human trials in many countries.
Spatial optimization of ground-based primary extraction routes using the BestWay decision support system
Authors: Flisberg Patrik , Rönnqvist Mikael , Willén Erik , Frisk Mikael , Friberg Gustav
Published: October 2020

Improving productivity in forest logging operations while reducing negative impact on soil and streams has gained increasing attention. Positioning primary extraction routes is crucial in these efforts, as it has a huge impact on efficient and sustainable forwarder passages. To minimize the total forwarding distance and avoid steep terrain and impact on soil and water, we developed a decision support system, including a detailed optimization model and solution method. The main source of information consisted of a detailed digital terrain model, depth-to-water maps, and forest volume density. The information was supplemented with the extent of the stand, position of the landing(s), nature and culture conservation sites, and any known unavoidable crossings in the terrain (e.g., streams). Because fast solution time was a critical requirement, we developed a decomposition method based on Lagrangian relaxation. The system was evaluated in two case studies in Sweden. In the first case, the optimization model performance was analyzed at 30 final harvesting sites. In the second case, experienced forest company staff evaluated the primary extraction routes at 19 harvest sites in operational conditions. The results indicated that the model allowed for faster planning, shorter driving distances, and the potential to reduce negative impact on soil and water.
Cherenkov-channeling radiation by relativistic muons in crystals
Authors: Korotchenko K. B. , Rozhkova E. I. , Dabagov S. B.
Published: October 2020

In this work we analyse Cherenkov radiation by relativistic muons, positive and negative, channeled in optically transparent diamond and silicon crystals in comparison with ordinary Cherenkov radiation. We have shown that the maxima in the spectral angular distributions for both types of radiation are revealed at the derivative extrema for the media refractive index, while, due to the difference in scattering of positively and negatively charged particles at crystal channeling, the number of Cherenkov photons emitted by channeled positive muons might be over the one for negative muons. We have demonstrated that Cherenkov radiation by quasi free projectiles is described as one limiting approximation of a general expression for Cherenkov radiation by channeled projectiles, which takes into account non-zero derivative of the refractive index. The last may result in essential increase of radiation intensity.
FINANCIAL INCLUSION, INSTITUTIONAL QUALITY AND FINANCIAL DEVELOPMENT: EMPIRICAL EVIDENCE FROM OIC COUNTRIES
Authors: ALI MINHAJ , NAZIR MUHAMMAD IMRAN , HASHMI SHUJAHAT HAIDER , ULLAH WAJEEH
Published: October 2020

This unique study examines the moderation effect of institutional quality (IQ) on the relationship between financial inclusion (FI) and financial development (FD) of 45 Organization of Islamic Cooperation (OIC) countries. For empirical analysis, panel data are used for the period 2000–2016. We use the Arellano–Bond generalized method of moments (GMM) and two-stage least-squares (2SLS) method in our estimations to draw multidimensional results. The empirical results confirm the significant positive relationship between FI, IQ and FD. Interestingly, we find that IQ moderates FI and has a significant positive impact on FD. Our findings are robust to alternative econometric specifications of FI, IQ and FD. Therefore, policymakers must sensibly understand the pivotal role of FI and IQ in establishing sustainable future development of OIC countries.