bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of grip strength with retinal and choroidal thickness in patients with type 2 diabetes mellitus without retinopathy: a cross-sectional study
Authors: Qiu Zihan , Wang Wei , Tan Yan , He Miao , Wang Langhua , Li Yuting , Gong Xia , Huang Wenyong 
Published: July 2020

ObjectiveTo evaluate the associations of grip strength with retinal or choroidal thickness in patients with type 2 diabetes mellitus without retinopathy.DesignObservational study-cross-sectional design.Setting and participantsThis study included the Chinese patients with type 2 diabetes without retinopathy registered in the community health system in Guangzhou, China.MeasuresThe grip strength in both hands were measured by using a dynamometer. The retinal and choroidal thickness in macular region stratified by Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were measured by a swept-source optical coherence tomography.ResultsA total of 1029 patients were included. Both retinal thickness and choroidal thickness decreased with the lower quartile of grip strength. Regression analyses indicated that the average retinal and choroidal thickness increased by 0.14 µm (95% CI: 0.03 to 0.25 µm, p=0.011) and 0.57 µm (95% CI: 0.03 to 1.11 µm, p=0.037), respectively, for each additional kilogram of grip strength following adjustment for age and sex. Further adjustments were made for axial length, haemoglobin A1c, length of time the patient had diabetes, insulin usage, height, weight and systolic and diastolic blood pressure, which resulted in an average retinal and choroidal thickness increase of 0.13 µm (95% CI: 0.02 to 0.24 µm, p=0.024) and 0.65 µm (95% CI: 0.13 to 1.16 µm, p=0.013), respectively, for each additional kilogram of grip strength. Consistent results were obtained in the analyses in ETDRS 9 sectors.ConclusionLower hand grip strength was found to be significantly associated with thinner retinal and choroidal layers in patients with diabetes. Grip strength may provide a useful and easily administered indicator of retinal status in patients with diabetes.
Neutrophil–lymphocyte ratio across psychiatric diagnoses: a cross-sectional study using electronic health records
Authors: Brinn Aimee , Stone James 
Published: July 2020

ObjectivesThe main objective of this study was to compare neutrophil–lymphocyte ratio (NLR), a marker of systemic inflammation, between patients diagnosed with International Classification of Diseases 10th Revision (ICD-10) psychiatric disorders and control participants.DesignA cross-sectional methodology was employed to retrospectively analyse electronic health records and records derived from a national health survey.SettingA secondary mental healthcare service consisting of four boroughs in South London.ParticipantsA diverse sample of 13 888 psychiatric patients extracted from South London and Maudsley electronic health records database and 3920 control participants extracted from National Health and Nutrition Survey (2015–2016) were included in the study.Primary and secondary outcome measuresPrimary: NLR levels in patients with mental health diagnoses, NLR between patients with different mental health diagnoses. Secondary: relationship of NLR to length of hospitalisation and to mortality.ResultsNLR was elevated compared with controls in patients with diagnoses including dementia, alcohol dependence, schizophrenia, bipolar affective disorder, depression, non-phobic anxiety disorders and mild mental retardation (p<0.05). NLR also correlated with age, antipsychotic use and hypnotic use. NLR was found to be higher in individuals of ‘white’ ethnicity and lower in individuals of ‘black’ ethnicity. Elevated NLR was associated with increased mortality (β=0.103, p=2.9e−08) but not with hospital admissions or face-to-face contacts.ConclusionsElevated NLR may reflect a transdiagnostic pathological process occurring in a subpopulation of psychiatric patients. NLR may be useful to identify and stratify patients who could benefit from adjunctive anti-inflammatory treatment.
Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit
Authors: Azimaraghi Omid , Hammer Maximilian , Santer Peter , Platzbecker Katharina , Althoff Friederike C , Patrocinio Maria , Grabitz Stephanie D , Wongtangman Karuna , Rumyantsev Sandra , Xu Xinling , Schaefer Maximilian S , Fuller Patrick M , Subramaniam Balachundhar , Eikermann Matthias 
Published: July 2020

IntroductionInsomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.Methods and analysisIn this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality.Ethics and disseminationEthics approval was obtained through the ‘Committee on Clinical Investigations’ at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals.Trial registration numberThis trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).
Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland
Authors: McCabe John Joseph , Giannotti Nicola , McNulty Jonathan , Collins Sean , Coveney Sarah , Murphy Sean , Barry Mary , Harbison Joseph , Cronin Simon , Williams David , Horgan Gillian , Dolan Eamon , Cassidy Tim , McDonnell Ciaran , Kavanagh Eoin , Foley Shane , O'Connell Martin , Marnane Michael , Kelly Peter 
Published: July 2020

PurposeInflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke.ParticipantsThe Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%–99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts.Findings to dateWe have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date.Future plansThe primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic ‘culprit’ carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.
‘Did I pass the licensing exam?’ aspects influencing migrant physicians’ results: a mixed methods study
Authors: Sturesson Linda , Heiding Andreas , Olsson Daniel , Stenfors Terese 
Published: July 2020

ObjectivesMigrant physicians (MPs) who wish to practise their profession in a new country often must undergo a recertification process, including a licensing exam. In many cases, this is the same licensing exam used for peers educated within the country; however, the pass rate of MPs is usually lower. This study aimed to explore MPs exam results, focusing on MPs that had participated in a complementary programme (CPP) for physicians with a medical degree from outside the European Union/European Economic Area (EU/EEA), and aspects that may influence these.MethodsMixed methods were applied. The data consisted of 2013 to 2019 licensing exam results of 564 physicians in Sweden that were educated outside of the EU. The data was analysed using linear and logistic regression analysis. Further, 14 interviews with MPs were conducted and thematically analysed.ResultsAn interaction between age and CPP participation was found for both the total score in per cent (p=0.01) and for the proportion failing their first attempt (p=0.04). Age was found to be a very strong predictor for failing on the first attempt, with those 45 and older failing on the first attempt in 72 and 82 per cent for CPP and non-CPP participants, respectively. Interview data was categorised into two themes: preparations and biographical aspects, and the exam and exam situation.ConclusionsAge seems to be an important predictor for failing the first attempt. MPs have had less time to familiarise themselves with the exam type and the language used on the exam. To improve exam results, MPs used different strategies and tools, that is, studying with nationally trained physicians, and using old exams and a web-based study tool consisting of common exam subjects. At the same time, these strategies and tools have also become mediators in the socialisation of MPs into the exam context.
Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19
Authors: Zuo Tao , Liu Qin , Zhang Fen , Lui Grace Chung-Yan , Tso Eugene YK , Yeoh Yun Kit , Chen Zigui , Boon Siaw Shi , Chan Francis KL , Chan Paul KS , Ng Siew C 
Published: July 2020

ObjectiveAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19.DesignWe performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity.ResultsSeven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3’ vs 5’ end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3’ vs 5’ end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA.ConclusionThis pilot study provides evidence for active and prolonged ‘quiescent’ GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.
Genetic variations in the human severe acute respiratory syndrome coronavirus receptorACE2and serine proteaseTMPRSS2
Authors: Fujikura Kohei , Uesaka Kazuma 
Published: July 2020

AimsThe recent emergence of novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health emergency. The coronaviral entry requires the spike (S)-protein for attachment to the host cell surface, and employs human angiotensin-converting enzyme 2 (hACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S-protein priming. Although coronaviruses undergo evolution by mutating themselves, it is also essential to know the host genetic factors. Here, we describe the single nucleotide variations (SNVs) in humanACE2andTMPRSS2.MethodsThe genetic variants derived from five population-sequencing projects were classified by variant type, allele frequency (AF), ethnic group and estimated pathogenicity. The SNVs in SARS-CoV-2/hACE2 contact residues were investigated. The genetic variability was normalised using non-linear regression and the total number of SNVs was estimated by the derived formulas.ResultsWe detected 349 and 551 SNVs inACE2andTMPRSS2, respectively, in a total of 156 513 individuals. The vast majority (>97%) of the SNVs were very rare (AF <0.1%) and population-specific, and were computationally estimated to be more frequently deleterious than the SNVs with high AF. These SNVs were distributed throughout the coding regions; someACE2 variants were located in the SARS-CoV-2/hACE2 contact residues, with a hemizygous state occurring in males. Using regression analysis, the total numbers of genetic variations inACE2andTMPRSS2were 1.1×103and 1.5×103, respectively, for a population of one million people.ConclusionThe majority of SNVs inACE2andTMPRSS2are rare, population-specific and deleterious, and a multitude of very rare SNVs may explain different susceptibility to SARS-CoV-2.
14 Pathological oscillatory activity in Parkinson’s disease; what does it mean and how should we treat it?
Authors: Brown Peter 
Published: July 2020

Professor Peter Brown is Professor of Experimental Neurology and Director of the Medical Research Council Brain Network Dynamics Unit at the University of Oxford. Prior to 2010 he was a Professor of Neurology at University College London.For decades we have had cardiac pacemakers that adjust their pacing according to demand and yet therapeutic adaptive stimulation approaches for the central nervous system are still not clinically available. Instead, to treat patients with advanced Parkinson’s disease we stimulate the basal ganglia with fixed regimes, unvarying in frequency or intensity. Although effective, this comes with side-effects and in terms of sophistication this treatment approach could be compared to having central heating system on all the time, regardless of temperature. This talk will describe recent steps being taken to define the underlying circuit dysfunction in Parkinson’s and to improve deep brain stimulation by controlling its delivery according to the state of pathological activity.Evidence is growing that motor symptoms in Parkinson’s disease are due, at least in part, to excessive synchronisation between oscillating neurons. Recordings confirm bursts of oscillatory synchronisation in the basal ganglia centred around 20 Hz. The bursts of 20 Hz activity are prolonged in patients withdrawn from their usual medication and the dominance of these long duration bursts negatively correlates with motor impairment. Longer bursts attain higher amplitudes, indicative of more pervasive oscillatory synchronisation within the neural circuit. In contrast, in heathy primates and in treated Parkinson’s disease bursts tend to be short. Accordingly, it might be best to use closed-loop controlled deep brain stimulation to selectively terminate longer, bigger, pathological beta bursts to both save power and to spare the ability of underlying neural circuits to engage in more physiological processing between long bursts. It is now possible to record and characterise bursts on-line during stimulation of the same site and trial adaptive stimulation. Thus far, this has demonstrated improvements in efficiency and side-effects over conventional continuous stimulation, with at least as good symptom control in Parkinsonian patients.
15 Stimulating the brain with sound: focused ultrasound for neuromodulation
Authors: Butler Chris 
Published: July 2020

Chris Butler studied medicine at Gonville and Caius College, Cambridge (1991–1994) and then at the University of Edinburgh (1994–1997). He conducted his PhD on the syndrome of transient epileptic amnesia under the supervision of Professor Adam Zeman. He worked as a post-doctoral fellow at the Memory and Aging Center, University of California at San Francisco and moved to Oxford in 2009. He was awarded a Clinician Scientist fellowship from the Medical Research Council in 2013.Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. TUS uses low intensity focused ultrasound delivered through the skull to cause direct modulation of neuronal function. In animal studies, TUS has been shown to modulate activity in several brain areas, including sensorimotor regions, visual cortex, frontal eye fields, anterior cingulate cortex and thalamic targets, resulting in behavioural as well as electrophysiological changes. Several studies have shown that TUS can be applied safely to healthy human participants to modulate behaviour and neural activity in brain regions including somatosensory, visual, and motor cortex as well as to deeper thalamic nuclei. These data have resulted in TUS emerging as a safe, potent, non-invasive brain stimulation tool, with better spatial accuracy and greater depth than established techniques such as transcranial magnetic or electrical stimulation. I will review these studies and discuss recent work of our own in which we studied, for the first time, TUS effects on higher-order human cortex.We investigated whether TUS can modulate higher-order visual processing both in superficial (middle temporal area (MT)) and deep (fusiform face area (FFA)) regions. Magnetic resonance imaging was used to map skull anatomy and functional regions of interest (MT and FFA) for each participant (n=16). To control for non-specific effects, auditory masking was applied during the tasks. EEG data were collected throughout. Auditory masking reduced subjective stimulation detection to chance level and abolished auditory evoked potentials. Ultrasonic stimulation of MT led to facilitation of visual motion detection in the contralateral hemifield, with no effect upon face identity detection. Stimulation of FFA did not affect visual motion detection performance. We show that TUS can be used in humans to modify behaviour and electrophysiological activity in higher-order visual pathways in a task- specific and anatomically precise manner.
9 Evaluation of an alcohol-related brain injury (ARBI) diagnostic service pilot
Authors: Jawahar Kaanthan , Zia Ul Haq Katshu Mohammad , Ellison James , Rhinds David 
Published: July 2020

Objectives/AimsTo pilot an ARBI diagnostic service within a community substance misuse team (delivered in partnership with the NHS by a 3rd sector organisation).BackgroundAlcohol-related brain injury (ARBI) is an umbrella term encompassing alcohol-related cognitive impairment, alcohol-related ‘dementias’, Wernicke’s encephalopathy and Korsakoff’s syndrome. It is the result of prolonged and harmful alcohol misuse, developing through direct neuronal damage from alcohol as well as chronic deficient states of vitamin B1 (thiamine). Anecdotally, it is felt that those affected by ARBI can struggle to access the necessary expertise for diagnosis and ongoing management.MethodsA widespread stakeholder engagement process led to the development of a standard operating procedure for the pilot service, utilising a process mapping technique. The service received referrals between September 2018 and January 2019. During this time, assessments were carried out in line with the standard operating procedure by the authors. Referrers were also asked to complete a questionnaire for their views on the service.ResultsReferrals were received from several sources within the host third sector organisation. Heterogeneity was seen in presentations and diagnoses made were not limited to ARBI. Referrers spoke highly of the service and how it had positively benefitted their patients going forwards, providing clarity around diagnoses and thus being able to access appropriate support going forwards. There was a clear need demonstrated for such a service.ConclusionsAnecdotally patients with ARBI are viewed as a marginalised group who struggle to access the necessary expertise for diagnosis and ongoing management. This service pilot was successful in filling that gap. Work is ongoing through discussions with local NHS healthcare system partners, including acute trusts, commissioners, mental health, the 3rd sector and Social Care, to devise a more sustainable pathway based upon this pilot service. At present, this is taking the form of an acute hospital ‘in-reach’ pathway to be trialled in an acute trust. This will provide the basis of a business case for a pathway across the STP footprint.