bluuebunny/crossref_metadata_2025 huggingface dataset:
Treating diabetes with electromagnetic fields
Authors: Xinyi Su
Published: October 2020

Exposure to electromagnetic fields increases insulin sensitivity in diabetic mice, with altered redox homeostasis mediated by mitochondrial superoxide.
Two Nearly Complete Nosocomial Pathogen Genome Sequences Reconstructed from Early-Middle 20th-Century Dental Calculus
Authors: Williams LaShanda , Cugini Carla , Duffy Siobain
Published: October 2020

Acinetobacter baumannii
and
Stenotrophomonas maltophilia
genomes were reconstructed from early-middle 20th-century human skeletal remains, maintained in natural history museums, using a metagenomic binning approach.
16S rRNA Gene Diversity of Bacterial Endophytes in Parasitic
Cuscuta campestris
and Its
Helianthus annuus
Host
Authors: Avila Adam T. , Van Laar Tricia A. , Constable John V. H. , Waselkov Katherine
Published: October 2020

Here, we report the results of 16S rRNA gene amplicon sequencing of bacterial endophytes from parasitized and unparasitized samples of the common sunflower (
Helianthus annuus
) and samples of its associated plant parasite field dodder (
Cuscuta campestris
), collected from one location in Fresno County, California (August 2017).
Telomere-to-Telomere Genome Assembly of Bursaphelenchus okinawaensis Strain SH1
Authors: Sun Simo , Shinya Ryoji , Dayi Mehmet , Yoshida Akemi , Sternberg Paul W. , Kikuchi Taisei
Published: October 2020

Bursaphelenchus okinawaensis
is a self-fertilizing, hermaphroditic, fungal-feeding nematode used as a laboratory model for the genus
Bursaphelenchus
, which includes the important pathogen
Bursaphelenchus xylophilus
. Here, we report the nearly complete genome sequence of
B. okinawaensis
. The 70-Mbp assembly contained six scaffolds (>11 Mbp each) with telomere repeats on their ends, indicating complete chromosomes.
Fossilization potential of marine assemblages and environments
Authors: Shaw Jack O. , Briggs Derek E.G. , Hull Pincelli M.
Published: October 2020

The fossil record provides the only direct record of the history of life, but it is an incomplete one. Discriminating between what is absent and what is simply not preserved is critical to macroevolutionary and macroecological inferences. A comparison of diversity data in over 20,000 modern marine assemblages from the Ocean Biogeographic Information System database (OBIS) with fossil occurrence data from the Paleobiology Database (PBDB) yielded a global assessment of assemblage-level fossilization potential. We used two different metrics, taxon fossilization potential and within-environment fossilization potential, to assess the proportion of taxa in a modern community with PBDB occurrences or with PBDB occurrences in the same environment, respectively. Taxon fossilization potential of marine genera varies between environments, from 34% in shallow and deep water to 44% in coral reefs, 51% on seamounts, and 15% in pelagic assemblages. Within-environment fossilization potential, in contrast, does not exceed 32% (in shallow water), a lower value than that obtained in other studies, and it may be zero (on seamounts and pelagic environments). These differences are mainly a product of representation in the rock record and sampling biases rather than taxon duration.
Autogenic delta progradation during sea-level rise within incised valleys
Authors: Guerit L. , Foreman B.Z. , Chen C. , Paola C. , Castelltort S.
Published: October 2020

Using a simple conceptual model of incised-valley evolution, we show that the classic sequence stratigraphic phenomenon of bayhead deltaic systems can be generated by purely autogenic progradation during the late stage of valley flooding. This transient “auto-advance” event occurs under conditions of constant base-level rise and sediment supply, and it results from a strong decrease of in-valley accommodation as base level rises toward the valley apex. We present a laboratory experiment to illustrate the plausibility of this mechanism and apply it to the incised valleys of the Trinity and Brazos Rivers (Texas, USA) as field case studies. Auto-advance can produce out-of-sequence regressive bayhead diastems during highstands similar to a transient change in allogenic forcing. Combined with other recent studies, our findings support the idea that mesoscale autogenic patterns are ubiquitous in the fluviodeltaic record and need to be more extensively incorporated into reconstructions of Earth surface evolution and reservoir models.
Integrating zircon trace-element geochemistry and high-precision U-Pb zircon geochronology to resolve the timing and petrogenesis of the late Ediacaran–Cambrian Wichita igneous province, Southern Oklahoma Aulacogen, USA
Authors: Wall Corey J. , Hanson Richard E. , Schmitz Mark , Price Jonathan D. , Donovan R. Nowell , Boro Joseph R. , Eschberger Amy M. , Toews Chelsea E.
Published: October 2020

The bimodal Wichita igneous province (WIP) represents the only exposed Ediacaran to Cambrian anorogenic magmatic assemblage present along the buried southern margin of Laurentia and was emplaced during rifting in the Southern Oklahoma Aulacogen prior to Cambrian opening of the southern Iapetus Ocean. Here, we establish the first high-precision U-Pb zircon geochronological framework for the province. Weighted mean 206Pb/238U dates from mafic and felsic rocks in the Wichita Mountains indicate emplacement in a narrow time frame from 532.49 ± 0.12 Ma to 530.23 ± 0.14 Ma. Rhyolite lavas in the Arbuckle Mountains farther east yield weighted mean 206Pb/238U dates of 539.20 ± 0.15 Ma and 539.46 ± 0.13 Ma. These dates for the WIP indicate that magmatism in the Southern Oklahoma Aulacogen postdated the ca. 540 Ma rift-drift transition along the Appalachian margin to the east. Whole-rock trace-element and isotopic geochemistry, supplemented by trace elements in zircon, tracks the evolution of magma sources during WIP petrogenesis. These data indicate that initial melting and assimilation of subcontinental mantle lithosphere by an uprising mantle plume were followed by increasing involvement of asthenospheric melts with time. We suggest that upwelling of this plume in the area of the Southern Oklahoma Aulacogen triggered an inboard jump of the spreading center active along the eastern margin of Laurentia, which led to separation of the Precordillera terrane (now located in Argentina) from the Ouachita embayment present in the southern Laurentian margin.
Regional-scale abrupt Mid-Holocene ice sheet thinning in the western Ross Sea, Antarctica
Authors: Jones R.S. , Whitmore R.J. , Mackintosh A.N. , Norton K.P. , Eaves S.R. , Stutz J. , Christl M.
Published: October 2020

Outlet glaciers drain the majority of ice flow in the Antarctic ice sheet. Theory and numerical models indicate that local bed topography can play a key role in modulating outlet glacier response to climate warming, potentially resulting in delayed, asynchronous, or enhanced retreat. However, the period of modern observations is too short to assess whether local or regional controls dominate ice sheet response on time scales that are critical for understanding ice sheet mass loss over this century and beyond. The recent geological past allows for insight into such centennial-scale ice sheet behavior. We present a cosmogenic surface-exposure chronology from Mawson Glacier, adjacent to a region of the Ross Sea that underwent dynamic marine-based ice sheet retreat following the Last Glacial Maximum. Our data record at least 220 m of abrupt ice thinning between 7.5 and 4.5 ka, followed by more gradual thinning until the last millennium. The timing, rates, and magnitudes of thinning at Mawson Glacier are remarkably similar to that documented 100 km to the south at Mackay Glacier. Together, both outlet glaciers demonstrate that abrupt deglaciation occurred across a broad region in the Mid-Holocene. This happened despite the complex bed topography of the western Ross Sea and implies an overarching external driver of retreat. When compared to regional sea-level and ocean-temperature changes, our data indicate that ocean warming most likely drove grounding-line retreat and ice drawdown, which then accelerated as a result of marine ice sheet instability.
Parental experience of prophylactic antibiotics
Authors: Hardman Simon Jonathan , Shackley Fiona , Condliffe Alison , Ugonna Kelechi , Lee Andrew
Published: October 2020

Background and objectives

Long-term prophylactic antibiotics are often used to prevent bacterial infections. However, supporting evidence for this is not always robust. Including parents in decisions relating to medication is key to medicines optimisation. Parental concern regarding medication is a major determinant of poor adherence. This study explores parental experiences of having a child prescribed prophylactic antibiotics and how that affects their antibiotic use behaviour.

Methods

We conducted a prospective, single-centre, exploratory, qualitative study at Sheffield Children’s Hospital. Through 15 interviews, involving 18 participants, we explored parental ‘lived experiences’ and attitudes towards azithromycin prophylaxis prescribed for various respiratory conditions. Thematic analysis was conducted.

Results

The overriding factor influencing parental decisions about the uptake of antibiotic prophylaxis is wanting their child to be well now. The main concern voiced by parents is that of antibiotic resistance given their children are high users of antibiotics. This is however seen as a problem for the future, not the present. Preparing families adequately helps prevent practical difficulties relating to medication. Facilitating ‘normalisation’ of prophylaxis through daily routines and minimising disruption to the family environment may reduce parental anxiety, promote adherence and result in easing of potential restrictions to the child’s daily activities.

Conclusion

Grounded in our deeper understanding, we propose a behavioural model that describes phases parents go through while having a child on prophylactic antibiotics. Time invested in holistically addressing the parental experience and having an awareness of potential issues parents face, may facilitate medication adherence, reduce anxieties and improve doctor-parent relationships.
Multiple evanescent white dot syndrome: clinical course and factors influencing visual acuity recovery
Authors: Bosello Francesca , Westcott Mark , Casalino Giuseppe , Agorogiannis Georgios , Micciolo Rocco , Rees Angela , Pavesio Carlos
Published: October 2020

Objective

To report the demographics and the clinical course of patients with multiple evanescent white dot syndrome (MEWDS) and to investigate for those factors which influence visual acuity (VA) recovery.

Methods

This is a retrospective single-centre observational study. Electronic medical records and retinal imaging of patients with a diagnosis of MEWDS with a minimum follow-up of 3 months were reviewed. Patients were categorised into three groups according to the VA at presentation and at the last visit: group 1 >0.48 logarithm of the minimum angle of resolution (LogMAR), group 2 ≤0.48 and ≥0.18 LogMAR and group 3 <0.18 LogMAR. All patients had non-invasive multimodal imaging including optical coherence tomography, near-infrared reflectance imaging and blue fundus autofluorescence at presentation and during follow-up.

Results

A total of 51 eyes from 51 patients (41 women, mean age 29.8±7.8 years) were included. Significantly more patients presented in the autumn (X2=8.69, p=0.034). The percentage of eyes recovering vision to 0.0 LogMAR or better was 80.3% (41/51). Worse presenting vision and young age at presentation were independent significant predictive variables for poorer final VA (p=0.002 and p=0.02, respectively). No imaging features were significantly predictive of complete versus incomplete recovery, but disc hyperfluorescence on fluorescein angiography was more common in those with incomplete recovery.

Conclusions

Although the majority of cases have a benign prognosis, the clinical spectrum of MEWDS includes incomplete visual recovery. In our series, poor presenting VA and young age were associated with poor VA outcome. Further study is warranted to confirm these findings.
Automated quantification of macular fluid in retinal diseases and their response to anti-VEGF therapy
Authors: Michl Martin , Fabianska Maria , Seeböck Philipp , Sadeghipour Amir , Haj Najeeb Bilal , Bogunovic Hrvoje , Schmidt-Erfurth Ursula Margarethe , Gerendas Bianca S
Published: October 2020

Aim

To objectively assess disease activity and treatment response in patients with retinal vein occlusion (RVO), neovascular age-related macular degeneration (nAMD) and centre-involved diabetic macular oedema (DME), using artificial intelligence–based fluid quantification.

Methods

Posthoc analysis of 2311 patients (11 151 spectral-domain optical coherence tomography volumes) from five clinical, multicentre trials, who received a flexible antivascular endothelial growth factor (anti-VEGF) therapy over a 12-month period. Fluid volumes were measured with a deep learning algorithm at baseline/months 1, 2, 3 and 12, for three concentric circles with diameters of 1, 3 and 6 mm (fovea, paracentral ring and pericentral ring), as well as four sectors surrounding the fovea (superior, nasal, inferior and temporal).

Results

In each disease, at every timepoint, most intraretinal fluid (IRF) per square millimetre was present at the fovea, followed by the paracentral ring and pericentral ring (p<0.0001). While this was also the case for subretinal fluid (SRF) in RVO/DME (p<0.0001), patients with nAMD showed more SRF in the paracentral ring than at the fovea up to month 3 (p<0.0001). Between sectors, patients with RVO/DME showed the highest IRF volumes temporally (p<0.001/p<0.0001). In each disease, more SRF was consistently found inferiorly than superiorly (p<0.02). At month 1/12, we measured the following median reductions of initial fluid volumes. For IRF: RVO, 95.9%/97.7%; nAMD, 91.3%/92.8%; DME, 37.3%/69.9%. For SRF: RVO, 94.7%/97.5%; nAMD, 98.4%/99.8%; DME, 86.3%/97.5%.

Conclusion

Fully automated localisation and quantification of IRF/SRF over time shed light on the fluid dynamics in each disease. There is a specific anatomical response of IRF/SRF to anti-VEGF therapy in all diseases studied.
Impact of tissue macrophage proliferation on peripheral and systemic insulin resistance in obese mice with diabetes
Authors: Morita Yutaro , Senokuchi Takafumi , Yamada Sarie , Wada Toshiaki , Furusho Tatsuya , Matsumura Takeshi , Ishii Norio , Nishida Saiko , Nishida Syuhei , Motoshima Hiroyuki , Komohara Yoshihiro , Yamagata Kazuya , Araki Eiichi
Published: October 2020

Introduction

Obesity-related insulin resistance is a widely accepted pathophysiological feature in type 2 diabetes. Systemic metabolism and immunity are closely related, and obesity represents impaired immune function that predisposes individuals to systemic chronic inflammation. Increased macrophage infiltration and activation in peripheral insulin target tissues in obese subjects are strongly related to insulin resistance. Using a macrophage-specific proliferation inhibition mouse model (mac-p27Tg), we previously reported that suppressed plaque inflammation reduced atherosclerosis and improved plaque stabilization. However, the direct evidence that proliferating macrophages are responsible for inducing insulin resistance was not provided.

Research design and methods

The mac-p27Tg mice were fed a high-fat diet, and glucose metabolism, histological changes, macrophage polarization, and tissue functions were investigated to reveal the significance of tissue macrophage proliferation in insulin resistance and obesity.

Results

The mac-p27Tg mice showed improved glucose tolerance and insulin sensitivity, along with a decrease in the number and ratio of inflammatory macrophages. Obesity-induced inflammation and oxidative stress was attenuated in white adipose tissue, liver, and gastrocnemius. Histological changes related to insulin resistance, such as liver steatosis/fibrosis, adipocyte enlargement, and skeletal muscle fiber transformation to fast type, were ameliorated in mac-p27Tg mice. Serum tumor necrosis factor alpha and free fatty acid were decreased, which might partially impact improved insulin sensitivity and histological changes.

Conclusions

Macrophage proliferation in adipose tissue, liver, and skeletal muscle was involved in promoting the development of systemic insulin resistance. Controlling the number of tissue macrophages by inhibiting macrophage proliferation could be a therapeutic target for insulin resistance and type 2 diabetes.
Bacterial versus non-bacterial infections: a methodology to support use-case-driven product development of diagnostics
Authors: Escadafal Camille , Geis Steffen , Siqueira A M , Agnandji Selidji T , Shimelis Techalew , Tadesse Birkneh Tilahun , Massinga Loembé Marguerite , Harris Victoria , Fernandez-Carballo B Leticia , Macé Aurélien , Ongarello Stefano , Rodriguez William , Dittrich Sabine
Published: October 2020

Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study’s demographics, the causes of fever identified and the performance of selected biomarkers.
Geospatial evaluation of trade-offs between equity in physical access to healthcare and health systems efficiency
Authors: Iyer Hari S , Flanigan John , Wolf Nicholas G , Schroeder Lee Frederick , Horton Susan , Castro Marcia C , Rebbeck Timothy R
Published: October 2020

Introduction

Decisions regarding the geographical placement of healthcare services require consideration of trade-offs between equity and efficiency, but few empirical assessments are available. We applied a novel geospatial framework to study these trade-offs in four African countries.

Methods

Geolocation data on population density (a surrogate for efficiency), health centres and cancer referral centres in Kenya, Malawi, Tanzania and Rwanda were obtained from online databases. Travel time to the closest facility (a surrogate for equity) was estimated with 1 km resolution using the Access Mod 5 least cost distance algorithm. We studied associations between district-level average population density and travel time to closest facility for each country using Pearson’s correlation, and spatial autocorrelation using the Global Moran’s I statistic. Geographical clusters of districts with inefficient resource allocation were identified using the bivariate local indicator of spatial autocorrelation.

Results

Population density was inversely associated with travel time for all countries and levels of the health system (Pearson’s correlation range, health centres: −0.89 to −0.71; cancer referral centres: −0.92 to −0.43), favouring efficiency. For health centres, negative spatial autocorrelation (geographical clustering of dissimilar values of population density and travel time) was weaker in Rwanda (−0.310) and Tanzania (−0.292), countries with explicit policies supporting equitable access to rural healthcare, relative to Kenya (−0.579) and Malawi (−0.543). Stronger spatial autocorrelation was observed for cancer referral centres (Rwanda: −0.341; Tanzania: −0.259; Kenya: −0.595; Malawi: −0.666). Significant geographical clusters of sparsely populated districts with long travel times to care were identified across countries.

Conclusion

Negative spatial correlations suggested that the geographical distribution of health services favoured efficiency over equity, but spatial autocorrelation measures revealed more equitable geographical distribution of facilities in certain countries. These findings suggest that even when prioritising efficiency, thoughtful decisions regarding geographical allocation could increase equitable physical access to services.
Prevalence of tobacco use, exposure to secondhand smoke and knowledge on smoking cessation among students of health professions in Central Greece: a cross-sectional study
Authors: Samara Athina A , Rachiotis George , Pettemeridou Sofia , Papastamatiou Konstantinos , Tourlakopoulos Konstantinos , Chelioti Eythimia , Katsioulis Antonis , Hadjichristodoulou Christos S
Published: October 2020

Objectives

The aim of this study was to assess the prevalence of tobacco use and exposure to secondhand smoke among students of health professions (SHPs) and determine possible risk factors for current smoking. In addition, we sought to investigate the level of students’ knowledge regarding smoking cessation.

Design

Cross-sectional.

Setting

Central Greece.

Participants

A convenient sample of 822 SHP volunteers were used, composed of 365 medical students, 123 students from a biochemistry department, 71 students from a nursing department, 176 from medical laboratory department and 84 students from a veterinary medicine department.

Primary and secondary outcome measures

We investigated the prevalence of current smoking and secondhand smoke, their determinants and SHP’s knowledge and attitudes regarding smoking cessation. Univariate and logistic regression statistical analysis were used in order to identify risk factors associated with current smoking.

Results

The prevalence of current smoking was estimated at 23.5% (95% CI 20.7% to 26.5%), while 49% of current smokers reported they wanted to quit smoking. The prevalence of current e-cigarette use was 1.2%. In addition, 96.5% (95% CI 94.9% to 97.5%) of SHP have been exposed to secondhand smoke at least 1 day per week. Logistic regression analysis showed that increasing age (p<0.001), alcohol consumption (p<0.001) and exposure to secondhand smoke in the home (p<0.001) were independent risk factors for current smoking. Notably, only 11.6% of the participants had learnt about methods to be used for smoking cessation.

Conclusions

Our results underline the need for integrated tobacco control initiatives that should discourage tobacco use among SHP, promote smoke free schools of health science, and implement programs that train SHP in effective cessation-counseling techniques.
Cardiovascular disease risk factors among school children of Bangladesh: a cross-sectional study
Authors: Islam T M Manjurul , Banik Palash Chandra , Barua Lingkan , Shariful Islam Sheikh Mohammed , Chowdhury Shahanaz , Ahmed M S A Mansur
Published: October 2020

Objective

Primarily, we assessed the distribution of cardiovascular disease (CVD) risk factors among school children living in urban and rural areas of Bangladesh. In addition to this, we sought the association between place of residence and modifiable CVD risk factors among them.

Design, setting and participants

This cross-sectional study was conducted among 854 school children (aged 12–18 years) of Bangladesh. Ten public high schools (five from Dhaka and five from Sirajgonj district) were selected randomly and subjects from those were recruited conveniently. To link the family milieu of CVD risk factors, a parent of each children was also interviewed.

Primary and secondary outcome measures

Distribution of CVD risk factors was measured using descriptive statistics as appropriate. Again, a saturated model of binary logistic regression was used to seek the association between place of residence and modifiable CVD risk factors.

Results

Mean age of the school children was 14.6±1.1 years and more than half (57.6%) were boys. Overall, 4.4% were currently smoker (urban—3.5%, rural—5.2%) with a strong family history of smoking (42.2%). Similar proportion of school children were identified as overweight (total 9.8%, urban 14.7%, rural 5%) and obese (total 9.8%, urban 16.8%, rural 2.8%) with notable urban-rural difference. More than three-fourth (80%) of them were physically inactive with no urban-rural variation. Only 2.4% consumed recommended fruits and/ or vegetables (urban—3.1%, rural—1.7%). In the adjusted model, place of residence had higher odds for having several modifiable CVD risk factors: current smoking (OR: 1.807, CI 0.872 to 3.744), inadequate fruits and vegetables intake (OR: 1.094, CI 0.631 to 1.895), physical inactivity (OR: 1.082, CI 0.751 to 1.558), overweight (OR: 3.812, CI 2.245 to 6.470) and obesity (OR: 7.449, CI 3.947 to 14.057).

Conclusions

Both urban and rural school children of Bangladesh had poor CVD risk factors profile that demands further nation-wide large scale study to clarify the current findings more precisely.
Women’s health inThe BMJ: a data science history
Authors: Hamulyák Eva N , Brockmeier Austin J , Killas Johanna D , Ananiadou Sophia , Middeldorp Saskia , Leroi Armand M
Published: October 2020

Objective

To determine how the representation of women’s health has changed in clinical studies over the course of 70 years.

Design

Observational study of 71 866 research articles published between 1948 and 2018 inThe BMJ.

Main outcome measures

The incidence of women-specific health topics over time. General linear, additive and segmented regression models were used to estimate trends.

Results

Over 70 years, the overall odds that a word in aBMJresearch article was ‘woman’ or ‘women’ increased by an annual factor of 1.023, but this rate of increase varied by clinical specialty with some showing little or no change. The odds that an article was about some aspect of women-specific health increased much more slowly, by an annual factor of 1.004. The incidence of articles about particular areas of women-specific medicine such as pregnancy did not show a general increase, but rather fluctuated over time. The incidence of articles making any mention of women, gender or sex declined between 1948 and 2005, after which it rose steeply so that by 2018 few papers made no mention of them at all.

Conclusions

Over time women have become ever more prominent inBMJresearch articles. However, the importance of women-specific health topics has waxed and waned as researchers responded ephemerally to medical advances, public health programmes, and sociolegal changes. The appointment of a woman editor-inchief in 2005 may have had a dramatic effect on whether women were mentioned in research articles.
IMAGINE Network’s Mind And Gut Interactions Cohort (MAGIC) Study: a protocol for a prospective observational multicentre cohort study in inflammatory bowel disease and irritable bowel syndrome
Authors: Moayyedi Paul , MacQueen Glenda , Bernstein Charles N , Vanner Stephen , Bercik Premysl , Madsen Karen L , Surette Michael , Rioux John D , Dieleman Levinus A , Verdú Elena , de Souza Russell J , Otley Anthony , Targownik Laura , Lavis John , Cunningham Jennifer , Marshall Deborah A , Zelinsky Sandra , Fernandes Aida
Published: October 2020

Introduction

Gut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome.

Methods and analysis

This 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity.

Ethics and dissemination

Approval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.

Trial registration number:NCT03131414
Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions
Authors: Lyons Jane , Akbari Ashley , Torabi Fatemeh , Davies Gareth I , North Laura , Griffiths Rowena , Bailey Rowena , Hollinghurst Joseph , Fry Richard , Turner Samantha L , Thompson Daniel , Rafferty James , Mizen Amy , Orton Chris , Thompson Simon , Au-Yeung Lee , Cross Lynsey , Gravenor Mike B , Brophy Sinead , Lucini Biagio , John Ann , Szakmany Tamas , Davies Jan , Davies Chris , Thomas Daniel Rh , Williams Christopher , Emmerson Chris , Cottrell Simon , Connor Thomas R , Taylor Chris , Pugh Richard J , Diggle Peter , John Gareth , Scourfield Simon , Hunt Joe , Cunningham Anne M , Helliwell Kathryn , Lyons Ronan
Published: October 2020

Introduction

The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions.

Methods and analysis

Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection.

Ethics and dissemination

The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.
Cognitive–behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a randomised controlled trial
Authors: Malik Sadaf , Asprusten Tarjei Tørre , Pedersen Maria , Mangersnes Julie , Trondalen Gro , van Roy Betty , Skovlund Eva , Wyller Vegard Bruun
Published: October 2020

Background

Cognitive–behavioural therapy (CBT) is effective in chronic fatigue (CF) syndrome. However, CBT has not been investigated in postinfectious CF, nor is it known whether addition of therapeutic elements from other disciplines might be useful. We explored combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents.

Methods

Adolescents (12–20 years old) participating in a postinfectious cohort study who developed CF 6 months after an acute EBV infection were eligible for the present study. A combined CBT and music therapy programme (10 therapy sessions and related homework) was compared with care as usual in a randomised controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects, but the study was underpowered regarding efficacy. Total follow-up time was 15 months. Power analyses suggested that 120 participants would be needed in order to detect a moderate effect size.

Results

A total of 91 individuals with postinfectious CF were eligible, and a total of 43 were included (21 intervention group, 22 control group). Concern regarding school absence due to therapy sessions was the main reason for declining participation. Seven individuals left the study during the first 3 months, leaving 15 in the intervention group and 21 in the control group at 3 months follow-up. No harmful effects were recorded, and compliance with appointment was high. In intention-to-treat analyses, the primary endpoint (number of steps/day) did not differ significantly between the intervention group and the control group (difference (95% CI) =–1298 (–4874 to 2278)). Secondary outcome measures were also not significantly different among the two groups.

Conclusion

An intervention study of combined CBT and music therapy in postinfectious CF is feasible. A fully powered trial is needed to evaluate efficacy; participants’ concern regarding school absence should be properly addressed to secure recruitment.

Trial registration number

ClinicalTrials ID:NCT02499302, registered July 2015.
FXR in the dorsal vagal complex is sufficient and necessary for upper small intestinal microbiome-mediated changes of TCDCA to alter insulin action in rats
Authors: Zhang Song-Yang , Li Rosa J W , Lim Yu-Mi , Batchuluun Battsetseg , Liu Huiying , Waise T M Zaved , Lam Tony K T
Published: October 2020

Objective

Conjugated bile acids are metabolised by upper small intestinal microbiota, and serum levels of taurine-conjugated bile acids are elevated and correlated with insulin resistance in people with type 2 diabetes. However, whether changes in taurine-conjugated bile acids are necessary for small intestinal microbiome to alter insulin action remain unknown.

Design

We evaluated circulating and specifically brain insulin action using the pancreatic-euglycaemic clamps in high-fat (HF) versus chow fed rats with or without upper small intestinal healthy microbiome transplant. Chemical and molecular gain/loss-of-function experiments targeting specific taurine-conjugated bile acid-induced changes of farnesoid X receptor (FXR) in the brain were performed in parallel.

Results

We found that short-term HF feeding increased the levels of taurochenodeoxycholic acid (TCDCA, an FXR ligand) in the upper small intestine, ileum, plasma and dorsal vagal complex (DVC) of the brain. Transplantation of upper small intestinal healthy microbiome into the upper small intestine of HF rats not only reversed the rise of TCDCA in all reported tissues but also enhanced the ability of either circulating hyperinsulinaemia or DVC insulin action to lower glucose production. Further, DVC infusion of TCDCA or FXR agonist negated the enhancement of insulin action, while genetic knockdown or chemical inhibition of FXR in the DVC of HF rats reversed insulin resistance.

Conclusion

Our findings indicate that FXR in the DVC is sufficient and necessary for upper small intestinal microbiome-mediated changes of TCDCA to alter insulin action in rats, and highlight a previously unappreciated TCDCA-FXR axis linking gut microbiome and host insulin action.
Enjoyment of life predicts reduced type 2 diabetes incidence over 12 years of follow-up: findings from the English Longitudinal Study of Ageing
Authors: Panagi Laura , Hackett Ruth A , Steptoe Andrew , Poole Lydia
Published: October 2020

Background

Subjective well-being appears to be associated with reduced risk of type 2 diabetes (T2D). However, it is unknown whether this association is similar across different types of well-being. We examined the relationship between hedonic and eudaimonic well-being and incident T2D, and explored the role of sociodemographic, behavioural and clinical factors in these associations.

Methods

We used data from 4134 diabetes-free participants from the English Longitudinal Study of Ageing (mean age =64.97). Enjoyment of life and purpose in life were assessed using items from the CASP-19 to reflect hedonic and eudaimonic well-being, respectively. Participants reported T2D diagnosis over 12 years. We used Cox proportional hazards regression analyses and also explored the percentage of association explained by different covariates.

Results

Results revealed a protective role for enjoyment of life in T2D rate adjusting for sociodemographic (age, sex, wealth, ethnicity, marital status), behavioural (physical activity, smoking, alcohol consumption, body mass index) and clinical (hypertension, coronary heart disease and glycated haemoglobin) characteristics (HR =0.93, p=0.021, 95% CI (0.87, 0.99)). Sociodemographic, behavioural and clinical factors accounted for 27%, 27% and 18% of the association, respectively. The relationship between purpose in life and T2D was non-significant (adjusted HR =0.92, p=0.288, 95% CI (0.78, 1.08)).

Conclusion

This study illustrates how the link between subjective well-being and T2D varies between well-being components. It also demonstrates that sociodemographic, behavioural and clinical factors partially explain this association. Intervention studies examining whether changes in enjoyment of life can help delay T2D onset are warranted.
Factors Predicting Length of Stay in Patients Hospitalized for Acute Parotitis
Authors: Markovich Avinoam , Ronen Ohad
Published: October 2020

Acute suppurative parotitis (ASP) is an acute infection of the parotid gland that necessitates hospitalization in some patients. The aim of this study was to evaluate clinical laboratory values including hydration, nutritional status, inflammatory markers and age, and to compare them with duration of hospitalization of patients with ASP. This is a retrospective chart review in a tertiary academic center. We investigated the factors affecting length of hospitalization in patients admitted to Galilee Medical Center with a diagnosis of ASP between 2010 and 2018. Of the 60 patients with ASP included in the study, 24 were male. The average age of patients was 60, ranging from 18 to 99. We found statistically significant correlations between length of hospitalization and patient age (r=0.3), C reactive protein (r=0.3), white cell count (WCC) at presentation (r=0.3), blood urea nitrogen to creatinine ratio (BUN:Cr) (r=0.2), and platelet levels at discharge (r=0.4). Examination of these factors on multivariate analysis found hospitalization duration was exclusively affected by patients’ level of dehydration as represented by BUN:Cr. Patient age, WCC levels at presentation, and platelet levels were not found to be statistically significant. Treatment and interventions should be planned accordingly.
Role of AMPK/mTOR-independent autophagy in clear cell renal cell carcinoma
Authors: Radovanovic Milan , Vidicevic Sasenka , Tasic Jelena , Tomonjic Nina , Stanojevic Zeljka , Nikic Predrag , Vuksanovic Aleksandar , Dzamic Zoran , Bumbasirevic Uros , Isakovic Aleksandra , Trajkovic Vladimir
Published: October 2020

We examined the status and role of autophagy, a process of lysosomal recycling of cellular material, in clear cell renal cell carcinoma (ccRCC). Paired samples of tumor and adjacent non-malignant tissue were collected from 20 patients with ccRCC after radical nephrectomy. The mRNA levels of apoptosis ( BAD, BAX, BCL2, BCLXL, BIM) and autophagy ( ATG4, BECN1, GABARAP, p62, UVRAG) regulators were measured by RT-qPCR. The protein levels of autophagosome-associated LC3-II, autophagy receptor p62, apoptotic marker PARP, as well as phosphorylation of autophagy initiator Unc 51-like kinase 1 (ULK1), its activator AMP-activated protein kinase (AMPK) and 4EBP1, the substrate of ULK1 inhibitor mechanistic target of rapamycin (mTOR), were analyzed by immunoblotting. The mRNA levels of pro-apoptotic BAX, anti-apoptotic BCLXL and pro-autophagic ATG4, p62 and UVRAG were higher in ccRCC tumors. Autophagy induction was confirmed by an increase in phospho-ULK1 and degradation of the autophagic target p62, while apoptotic PARP cleavage was unaltered. AMPK phosphorylation was reduced and 4EBP1 phosphorylation was increased in ccRCC tissue. The expression of apoptosis regulators did not correlate with clinicopathological features of ccRCC. Conversely, high mRNA levels of ATG4, GABARAP and p62 were associated with lower tumor stage, as well as with smaller tumor size and better disease-specific 5-year survival ( ATG4 and p62). Accordingly, low p62 protein levels, corresponding to increased autophagic flux, were associated with lower tumor stage, reduced metastasis and improved 5-year survival. These data demonstrate that transcriptional induction of autophagy in ccRCC is accompanied by AMPK/mTOR-independent increase in ULK1 activation and autophagic flux, which might slow tumor progression and metastasis independently of apoptosis.
Biomarkers in functional movement disorders: a systematic review
Authors: Thomsen Birgitte Liang Chen , Teodoro Tiago , Edwards Mark J
Published: October 2020

Functional movement disorders (FMD) are proposed to reflect a specific problem with voluntary control of movement, despite normal intent to move and an intact neural capacity for movement. In many cases, a positive diagnosis of FMD can be established on clinical grounds. However, the diagnosis remains challenging in certain scenarios, and there is a need for predictors of treatment response and long-term prognosis.

In this context, we performed a systematic review of biomarkers in FMD. Eighty-six studies met our predefined criteria and were included.

We found fairly reliable electroencephalography and electromyography-based diagnostic biomarkers for functional myoclonus and tremor. Promising biomarkers have also been described for functional paresis, gait and balance disorders. In contrast, there is still a lack of diagnostic biomarkers of functional dystonia and tics, where clinical diagnosis is often also more challenging. Importantly, many promising findings focus on pathophysiology and reflect group-level comparisons, but cannot differentiate on an individual basis. Some biomarkers also require access to time-consuming and resource-consuming techniques such as functional MRI.

In conclusion, there are important gaps in diagnostic biomarkers in FMD in the areas of most clinical uncertainty. There is also is a lack of treatment response and prognostic biomarkers to aid in the selection of patients who would benefit from rehabilitation and other forms of treatment.
Study on sleep-wake disorders in patients with genetic and non-genetic amyotrophic lateral sclerosis
Authors: Sun Xiaohan , Zhao Ximeng , Liu Qing , Liu Shuangwu , Zhang Kang , Wang Zhi-li , Yang Xunzhe , Shang Liang , Huang Yan , Cui Liying , Zhang Xue
Published: October 2020

Objective

To study the frequency and clinical features of sleep disturbances in amyotrophic lateral sclerosis (ALS) patients and compare sleep disorders between ALS with and without mutations.

Methods

In this case–control study, 204 ALS patients and 206 controls were included. We evaluated sleep quality using Pittsburgh Sleep Quality Index (PSQI). Excessive daytime sleepiness (EDS) was diagnosed according to Epworth Sleepiness Scale (ESS). Other characteristics, including rapid eye movement sleep behaviour disorder, restless legs syndrome (RLS), cognitive and psychological impairments, were also evaluated. All ALS patients underwent whole exome sequencing analysis to screen for ALS mutations and were divided into genetic ALS and non-genetic ALS subgroups based on the genetic testing results.

Results

A total of 114 men and 90 women ALS patients, with a mean onset age of 53.5±9.9 years, were included in this study. There were 21 mutations detected, contributing to 46.6% of familial amyotrophic lateral sclerosis (FALS) and 7.4% of sporadic amyotrophic lateral sclerosis (SALS). The PQSI and ESS scores were higher in ALS patients than in controls (PSQI 6.0 (3.0,10.0) vs 3.5 (2.0,5.0) (p<0.01); ESS 6.0 (3.0,10.0) vs 4.0 (3.0,8.0) (p<0.01), respectively). RLS was more frequent in ALS patients than in controls (p<0.01). Genetic ALS patients were more likely to show EDS than non-genetic ALS patients (adjusted OR 5.2, p<0.01). Genetic ALS scored lower on Revised ALS Functional Rating Scale, and higher on PSQI and ESS than non-genetic ALS (p<0.01).

Conclusions

In the current study, ALS patients with mutations were more likely to have sleep-wake disturbances than were those without mutations. The former group may benefit more from sleep management.
Vivisection through the eyes of Wilkie Collins, HG Wells and John Galsworthy
Authors: Durey Jill Felicity
Published: October 2020

The article argues that, unlike Collins’ adamantly negative view towards vivisection in the latter half of the nineteenth century and approaching the end of his writing career and life, Wells and Galsworthy’s changing opinions responded to medical advances, reflected the dynamics of public opinion, and their own knowledge and experience at their time of writing. With its primary focus on Galsworthy, the study also explores the reactions of contemporary critics, readers, scientists and medical practitioners to these depictions of vivisection. Above all, the article argues that popular writers, particularly before modern multimedia, greatly influenced public attitudes towards changes in society, including medical research by vivisection. The ultimate change of heart towards vivisection by Nobel Prize winner Galsworthy, an indirect and eminent beneficiary of vivisection, the article concludes, would have boosted public acceptance and the cause of modern medicine.