bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal microvascular signs in COVID-19
Authors: Sim Ralene , Cheung Gemmy , Ting Daniel , Wong Edmund , Wong Tien Yin , Yeo Ian , Wong Chee Wai 
Published: March 2021

Background/aimsTo explore if retinal findings are associated with COVID-19 infection.MethodsIn this prospective cross-sectional study, we recruited participants positive for COVID-19 by nasopharyngeal swab, with no medical history. Subjects underwent retinal imaging with an automated imaging device (3D OCT-1 Maestro, Topcon, Tokyo, Japan) to obtain colour fundus photographs (CFP) and optical coherence tomographic (OCT) scans of the macula. Data on personal biodata, medical history and vital signs were collected from electronic medical records.Results108 patients were recruited. Mean age was 36.0±5.4 years. 41 (38.0%) had symptoms of acute respiratory infection (ARI) at presentation. Of 216 eyes, 25 (11.6%) had retinal signs—eight (3.7%) with microhaemorrhages, six (2.8%) with retinal vascular tortuosity and two (0.93%) with cotton wool spots (CWS). 11 eyes (5.1%) had hyper-reflective plaques in the ganglion cell-inner plexiform layer layer on OCT, of which two also had retinal signs visible on CFP (CWS and microhaemorrhage, respectively). There was no significant difference in the prevalence of retinal signs in symptomatic versus asymptomatic patients (12 (15.0%) vs 13 (9.6%), p=0.227). Patients with retinal signs were significantly more likely to have transiently elevated blood pressure than those without (p=0.03).ConclusionOne in nine had retinal microvascular signs on ocular imaging. These signs were observed even in asymptomatic patients with normal vital signs. These retinal microvascular signs may be related to underlying cardiovascular and thrombotic alternations associated with COVID-19 infection.
Importance of accounting for sibling age when examining the association between family size and early childhood cognition, language and emotional behaviour: a birth cohort study
Authors: Symeonides Christos , Vuillermin Peter J , Sciberras Emma , Senn Elizabeth , Thomson Sarah M , Wardrop Nicole , Anderson Vicki , Pezic Angela , Sly Peter D , Ponsonby Anne-Louise 
Published: March 2021

ObjectivesLarger sibships are associated with poorer cognitive and language outcomes but have different impacts on child emotional development. Previous studies have not taken into account sibling age, nor have impacts across multiple neurodevelopmental domains been considered in the same participant group. This study investigated the influence of family size indicators on early childhood cognitive, language and emotional-behavioural development. The effect of sibling age was considered by evaluating these relationships separately for different sibling age categories.DesignProspective birth cohort study.SettingParticipants in the Barwon Infant Study were recruited from two major hospitals in the Barwon region of Victoria, Australia, between 2010 and 2013 (n=1074 children).ParticipantsThe 755 children with any neurodevelopmental data at age 2–3 years excluding twins and those with an acquired neurodisability.Outcome measuresCognitive and language development was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition, and emotional-behavioural development was measured with the Child Behaviour Checklist for Ages 1½−5.ResultsGreater household size was associated with a reduced cognitive development score (adjusted mean difference (AMD) −0.66 per extra household member; 95% CI −0.96 to –0.37; p<0.001) without age-specific differences. However, poorer expressive language was only observed for exposure to siblings between 2–6 and 6–10 years older. Having siblings 2–6 years older was associated with less internalising behaviour (AMD −2.1 per sibling; 95% CI −3.1 to –1.0; p<0.001). These associations persisted after multiple comparison adjustment.ConclusionsThe influence of siblings on early childhood development varies substantially by sibling age and the neurodevelopmental outcome under study. Although family size alone appears important for cognitive development, age-specific findings emphasise the importance of sibling interaction in early childhood expressive language development and emotional behaviour.
Mindfulness-based programmes to reduce stress and enhance well-being at work: a realist review
Authors: Micklitz Katrin , Wong Geoff , Howick Jeremy 
Published: March 2021

ObjectivesTo understand how and why workplace mindfulness-based programmes (MBPs) work or do not work.DesignA realist review.Eligibility criteria for selectionWe considered any studies (experimental quasi-experimental, observational, qualitative and mixed-methods studies) of workplace MBPs as long as they provided data to explain our programme theories. All MBP formats and delivery modes were included.AnalysisConsistent with realist review methodology, we systematically screened and analysed data to explain how and why workplace MBPs work or do not work. These explanations were consolidated into a programme theory augmented by theories from organisational literature, such as conservation of resources theory.ResultsFindings from 75 primary studies suggest that workplace MBPs enable participants (including healthcare professionals) to deal more skillfully with stressful events and improve their well-being. The mechanisms involved can be grouped around awareness/self-regulation, acceptance/compassion, feeling permitted to take care of self, sense of growth and promise of goal attainment. In order for professionals to invest in an MBP and benefit from it, it is important that they feel safe to engage with self-care at work and share emotional difficulties among peers. It is also important that employees are able to link the programme and its activities to existing goals and practices. Concerns of being non-productive, of not getting work done or of being exposed in front of colleagues can result in strategic use of brief mindfulness exercises, non-adherence or drop-out.ConclusionsSimply offering an MBP to (healthcare) professionals in order to reduce stress and enhance well-being does not suffice. A supportive environment must exist in order for the programme’s benefits to be reaped.PROSPERO registration numberCRD42018086280.
Single-lead ECGs (AliveCor) are a feasible, cost-effective and safer alternative to 12-lead ECGs in community diagnosis and monitoring of atrial fibrillation
Authors: Bray Jonathan James Hyett , Lloyd Elin Fflur , Adenwalla Firdaus , Kelly Sarah , Wareham Kathie , Halcox Julian P J 
Published: March 2021

BackgroundCommunity management of atrial fibrillation (AF) often requires the use of electrocardiographic (ECG) investigation. Patients discharged following treatment of AF with fast ventricular response (fast AF) can require numerous ECGs to monitor rate and/or rhythm control. Single-lead ECGs have been proposed as a more convenient and relatively accurate alternative to 12-lead ECGs for rate/rhythm management and also diagnosis of AF. We aimed to examine the feasibility of using the AliveCor single-lead ECG monitor for diagnosis and monitoring of AF in the community setting.MethodsDuring the course of 6 months, this evaluation of a clinical service improvement pathway used the AliveCor in management of patients requiring (1) follow-up ECGs for AF with previously documented rapid ventricular rate or (2) ECG confirmation of rhythm where AF was suspected. Twelve AliveCor devices provided to the acute community medical team were used to produce 30 s ECG rhythm strips (iECG) that were electronically sent to an overreading physician.ResultsSeventy-four patients (mean age 82 years) were managed on this pathway. (1) The AliveCor was successfully used to monitor the follow-up of 37 patients with fast AF, acquiring a combined total of 113 iECGs (median 1.5 ±3.75 per patient). None of these patients required a subsequent 12-lead ECG and this approach saved an estimate of up to £134.49 per patient. (2) Of 53 patients with abnormal pulses, the system helped identify 8 cases of new onset AF and 19 cases of previously known AF that had reverted from sinus back into AF.ConclusionsWe have demonstrated that the AliveCor system is a feasible, cost-effective, time-efficient and potentially safer alternative to serial 12-lead ECGs for community monitoring and diagnosis of AF.
NHS staff mental health status in the active phase of the COVID-19 era: a staff survey in a large London hospital
Authors: Ike Ikenna David , Durand-Hill Matthieu , Elmusharaf Eiman , Asemota Nicole , Silva Elizabeth , White Elliott , Awad Wael I 
Published: March 2021

BackgroundExperiencing a pandemic can be very unsettling and may have a negative impact on the mental health of frontline healthcare workers (HCWs). This may have serious consequences for the overall well-being of HCWs, which in turn may adversely affect patient safety and the productivity of the institution.AimsWe designed a study to assess the prevalence of generalised anxiety disorder (GAD), depression and work-related stress experienced by the National Health Service staff in a large tertiary London hospital treating patients with COVID-19 during the current active phase of the COVID-19 era.MethodsAn anonymous survey was designed with demographic data and three questionnaires. The Generalised Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 were used to assess anxiety and depression, respectively. The Health and Safety Executive Management Standards Indicator Tool was used to assess work-related stress. Staff from multiple specialties embracing cardiothoracic surgery, cardiology, respiratory medicine, endocrinology, oncology, imaging, anaesthesia and intensive care at our hospital were asked to complete the questionnaire between 25 May and 15 June 2020.ResultsA total of 302 staff members (106 males and 196 females) completed the survey. The overall prevalence of GAD and depression was 41.4% and 42.7%, respectively. The prevalence of GAD and depression was significantly higher in females than in males and was statistically significant. Nurses were four times more likely to report moderate to severe levels of anxiety and depression as compared with doctors. Work-related stress was also observed to be prevalent in our surveyed population with the following standards: relationships, role, control and change showing a need for improvement.ConclusionsOur study presents early evidence suggestive of a high prevalence of GAD, depression and work-related stress in HCWs. It is imperative that coherent strategies are implemented to improve the healthcare work environment during this pandemic and mitigate further injury to the mental health status of the healthcare population.
Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis
Authors: Sapena Victor , Enea Marco , Torres Ferran , Celsa Ciro , Rios Jose , Rizzo Giacomo Emanuele Maria , Nahon Pierre , Mariño Zoe , Tateishi Ryosuke , Minami Tatsuya , Sangiovanni Angelo , Forns Xavier , Toyoda Hidenori , Brillanti Stefano , Conti Fabio , Degasperi Elisabetta , Yu Ming-Lung , Tsai Pei-Chien , Jean Kevin , El Kassas Mohamed , Shousha Hend Ibrahim , Omar Ashraf , Zavaglia Claudio , Nagata Hiroko , Nakagawa Mina , Asahina Yasuhiro , Singal Amit G , Murphy Caitlin , Kohla Mohamed , Masetti Chiara , Dufour Jean-François , Merchante Nicolas , Cavalletto Luisa , chemello liliana LC , POL Stanislas , Crespo Javier , Calleja Jose Luis , Villani Rosanna , Serviddio Gaetano , Zanetto Alberto , Shalaby Sarah , Russo Francesco Paolo , Bielen Rob , Trevisani Franco , Cammà Calogero , Bruix Jordi , Cabibbo Giuseppe , Reig Maria 
Published: March 2021

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).ConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.
Chimeric antigen receptor engineered NK cellular immunotherapy overcomes the selection of T-cell escape variant cancer cells
Authors: Lee Maxwell Y , Robbins Yvette , Sievers Cem , Friedman Jay , Abdul Sater Houssein , Clavijo Paul E , Judd Nancy , Tsong Edward , Silvin Chris , Soon-Shiong Patrick , Padget Michelle R , Schlom Jeffrey , Hodge James , Hinrichs Christian , Allen Clint 
Published: March 2021

BackgroundAs heterogeneous tumors develop in the face of intact immunity, tumor cells harboring genomic or expression defects that favor evasion from T-cell detection or elimination are selected. For patients with such tumors, T cell-based immunotherapy alone infrequently results in durable tumor control.MethodsHere, we developed experimental models to study mechanisms of T-cell escape and demonstrated that resistance to T-cell killing can be overcome by the addition of natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting programmed death ligand-1 (PD-L1).ResultsIn engineered models of tumor heterogeneity, PD-L1 CAR-engineered NK cells (PD-L1 t-haNKs) prevented the clonal selection of T cell-resistant tumor cells observed with T-cell treatment alone in multiple models. Treatment of heterogenous cancer cell populations with T cells resulted in interferon gamma (IFN-γ) release and subsequent upregulation of PD-L1 on tumor cells that escaped T-cell killing through defects in antigen processing and presentation, priming escape cell populations for PD-L1 dependent killing by PD-L1 t-haNKs in vitro and in vivo.ConclusionsThese results describe the underlying mechanisms governing synergistic antitumor activity between T cell-based immunotherapy that results in IFN-γ production, upregulation of PD-L1 on T-cell escape cells, and the use of PD-L1 CAR-engineered NK cells to target and eliminate resistant tumor cell populations.
Incremental role of CT coronary angiography in the assessment of left ventricular diastolic function
Authors: Lange Aleksandra , Huntress Harry , Steindl Jesse , Palka Przemyslaw 
Published: March 2021

ObjectiveTo determine whether Computed Tomography (CT) coronary angiography (CTCA) has clinical value for the assessment of left ventricular (LV) diastolic dysfunction (DD) beyond traditional information on coronary artery anatomy.MethodIn this retrospective study, a consecutive group of 72 patients (mean age 59±13 years)—who met the eligibility criteria of sinus rhythm, no significant valvular abnormalities, and who had transthoracic echocardiogram (TTE)—were analysed. The CTCA was prospectively triggered during diastole. Outcomes of interest were CTCA derived LV and left atrial (LA) volumes, diastolic expansion (DE) index: LV volume÷LA volume and DE fraction (DEF): [(LV volume–LA volume)÷LV volume]×100. TTE-LA volume was measured as maximum, minimum and pre-A. Studied patients were divided according to the current classification of LVDD as a reference standard. A small subgroup of nine patients underwent further invasive cardiac catheterisation.ResultsCTCA-LV and LA volumes were larger compared with TTE, 37%±20% and 11%±21%, respectively. CTCA-LA volume correlated well with all TTE-LA volumes (maximum: R2=0.58; pre-A wave: R2=0.39; minimum: R2=0.26; p<0.0001) with the smallest differences in maximum LA volume (9±32 mL; mean±2 SD). The DE and DEF correlated with both LA function and LVDD. DE >1.65 and DE <1.40 have good specificity (85% and 88%, respectively), and positive predictive value to differentiate LVDD. DE and DEF were dependent on the patients’ age but independent of other variables.ConclusionsCTCA derived diastasis volume indices can provide additional quantifiable information on LVDD.
Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats
Authors: Nalamolu Koteswara Rao , Chelluboina Bharath , Fornal Casimir A , Challa Siva Reddy , Pinson David M , Wang David Z , Klopfenstein Jeffrey D , Veeravalli Krishna Kumar 
Published: March 2021

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.
The effects of the Jenkyns Event on the radiation of Early Jurassic dinoflagellate cysts
Authors: Correia Vânia F. , Riding James B. , Duarte Luís V. , Fernandes Paulo , Pereira Zélia 
Published: March 2021

Abstract
This contribution is an overview of the Early Jurassic dinoflagellate cysts of the Lusitanian Basin in Portugal, with particular emphasis on the effects of the Jenkyns Event (Toarcian Oceanic Anoxic Event) on the evolution of this planktonic group. We review and discuss data from 214 samples from six Lower Jurassic successions (upper Sinemurian to upper Toarcian) in the Lusitanian Basin. The late Pliensbachian radiation of dinoflagellate cysts was well recognized in this basin. The pre-Jenkyns Event interval is highly productive, with maximum abundance and species richness values. However, this palaeoenvironmental perturbation severely affected the evolution of this group for the remainder of the Early Jurassic. The prolonged recovery of the dinoflagellates in the Toarcian following the Jenkyns Event is not typical of the northern regions (Arctic and Boreal realms), where new species began to evolve earlier compared with southern European basins.
Label-Free Deep Profiling of the Tumor Microenvironment
Authors: You Sixian , Chaney Eric J. , Tu Haohua , Sun Yi , Sinha Saurabh , Boppart Stephen A. 
Published: March 2021

AbstractLabel-free nonlinear microscopy enables nonperturbative visualization of structural and metabolic contrast within living cells in their native tissue microenvironment. Here a computational pipeline was developed to provide a quantitative view of the microenvironmental architecture within cancerous tissue from label-free nonlinear microscopy images. To enable single-cell and single-extracellular vesicle (EV) analysis, individual cells, including tumor cells and various types of stromal cells, and EVs were segmented by a multiclass pixelwise segmentation neural network and subsequently analyzed for their metabolic status and molecular structure in the context of the local cellular neighborhood. By comparing cancer tissue with normal tissue, extensive tissue reorganization and formation of a patterned cell–EV neighborhood was observed in the tumor microenvironment. The proposed analytic pipeline is expected to be useful in a wide range of biomedical tasks that benefit from single-cell, single–EV, and cell-to-EV analysis.Significance:The proposed computational framework allows label-free microscopic analysis that quantifies the complexity and heterogeneity of the tumor microenvironment and opens possibilities for better characterization and utilization of the evolving cancer landscape.
What is a Classic in History?
Authors: Aurell Jaume 
Published: March 2021

Abstract
What is the classic in history? What is a classic in historical writing? Very few historians and critics have addressed these questions, and when they have done so, it has been only in a cursory manner. These are queries that require some explanation regarding historical texts because of their peculiar ambivalence between science and art, content and form, sources and imagination, scientific and narrative language. Based on some examples of the Western historiographical tradition, I discuss in this article to what extent historians should engage the concept of the classic – as has been done for literary texts. If one assumes that the historical text is not only a referential account but also a narrative analogous to literary texts, then the concept of the classic becomes one of the keys for understanding the historical text – and may improve our understanding not only of historiography, but of history itself. I will argue in this article that it is possible to identify a category of the classic text in some historical writings, precisely because of the literarity they possess without losing their specific historical condition. Because of their narrative condition, historical texts share some of the features assigned to literary texts – that is, endurance, timelessness, universal meaningfulness, resistance to historical criticism, susceptibility to multiple interpretations, and ability to function as models. Yet, since historical texts do not construct imaginary worlds but reflect external realities, they also have to achieve some specific features according to this referential content – that is, surplus of meaning, historical use of metaphors, effect of contemporaneity without damaging the pastness of the past, and a certain appropriation of literariness. Without seeking to be normative or systematic, this article focuses on some specific features of the historical classic, offering a series of reflections to open rather than try to close a debate on this complex topic.