bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital scanned laser light‐sheet fluorescence lifetime microscopy with wide‐field time‐gated imaging
Authors: LI R. , LIU A. , WU T. , XIAO W. , TANG LI , CHEN LINGLING 
Published: April 2020

SummaryWe develop a multidimensional fluorescence imaging technique by implementing a wide‐field time‐gated fluorescence lifetime imaging into digital scanned laser light‐sheet microscopy (FLIM‐DSLM) to measure 3D fluorescence lifetime distribution in mesoscopic specimens with high resolution. This is achieved by acquiring a series of time‐gated images at different relative time delays with respect of excitation pulses at different depths. The lifetime is determined for each voxel by iteratively fitting to single exponential decay. The performance of the developed system is evaluated with the measurements of a lifetime reference Rhodamine 6G solution and a subresolution fluorescent bead phantom. We also demonstrate the application performances of this system to ex vivo and in vivo imaging of Tg(kdrl:EGFP) transgenic zebrafish embryos, illustrating the lifetime differences between the GFP signal and the autofluorescence signal. The results show that FLIM‐DSLM can be used for sample size up to a few millimetres and can be utilised as a powerful and robust method for biomedical research, for example as a readout of protein–protein interactions via Förster resonance energy transfer.
Synaptic withdrawal following nerve injury is influenced by postnatal maturity, muscle‐specific properties, and the presence of underlying pathology in mice
Authors: Mole Alannah J. , Bell Sarah , Thomson Alison K. , Dissanayake Kosala N. , Ribchester Richard R. , Murray Lyndsay M. 
Published: April 2020

AbstractAxonal and synaptic degeneration occur following nerve injury and during disease. Traumatic nerve injury results in rapid fragmentation of the distal axon and loss of synaptic terminals, in a process known as Wallerian degeneration (WD). Identifying and understanding factors that influence the rate of WD is of significant biological and clinical importance, as it will facilitate understanding of the mechanisms of neurodegeneration and identification of novel therapeutic targets. Here, we investigate levels of synaptic loss following nerve injury under a range of conditions, including during postnatal development, in a range of anatomically distinct muscles and in a mouse model of motor neuron disease. By utilising an ex vivo model of nerve injury, we show that synaptic withdrawal is slower during early postnatal development. Significantly more neuromuscular junctions remained fully innervated in the cranial nerve/muscle preparations analysed at P15 than at P25. Furthermore, we demonstrate variability in the level of synaptic withdrawal in response to injury in different muscles, with retraction being slower in abdominal preparations than in cranial muscles across all time points analysed. Importantly, differences between the cranial and thoracoabdominal musculature seen here are not consistent with differences in muscle vulnerability that have been previously reported in mouse models of the childhood motor neuron disease, spinal muscular atrophy (SMA), caused by depletion of survival motor neuron protein (Smn). To further investigate the relationship between synaptic degeneration in SMA and WD, we induced WD in preparations from the Smn2B/− mouse model of SMA. In a disease‐resistant muscle (rostral band of levator auris longus), where there is minimal denervation, there was no change in the level of synaptic loss, which suggests that the process of synaptic withdrawal following injury is Smn‐independent. However, in a muscle with ongoing degeneration (transvs. abdominis), the level of synaptic loss significantly increased, with the percentage of denervated endplates increasing by 33% following injury, compared to disease alone. We therefore conclude that the presence of a die‐back can accelerate synaptic loss after injury in Smn2B/− mice.
Saudi Teachers’ Perceptions of In‐Service Education and Training Addressing Attention‐Deficit/Hyperactivity Disorder
Authors: Abed Mohaned G. , Shackelford Todd K. 
Published: April 2020

AbstractWorldwide, 3.0–7.0 percent of school‐aged children meet criteria for a diagnosis of Attention‐Deficit/Hyperactivity Disorder (ADHD). In Saudi Arabia, ADHD appears to be more prevalent than the worldwide average, with estimates of 12.6–16.7 percent. Unfortunately, there is a relative dearth of research addressing ADHD and related training programs in Saudi Arabia. We investigated perceptions of teachers in Saudi elementary schools regarding current In‐Service Education and Training (INSET) programs addressing students diagnosed with ADHD. We interviewed 40 teachers (15 women and 25 men) from public elementary schools in Jeddah, Saudi Arabia. The findings highlight the need to develop INSET programs specifically addressing best practices for managing and educating students diagnosed with ADHD.
Toxic Environments and the Embedded Psyche
Authors: Lock Margaret 
Published: April 2020

AbstractimageA discussion of the recent transition to a new geological epoch, the Anthropocene, opens this article. The need to declare a new era has been declared necessary by geologists, together with other scientists and critical commentators due to the inordinate amount of human‐made destruction being imposed on the globe and its inhabitants. This destruction disproportionally effects those who are economically deprived and experience discrimination. An account of the recognition and routinization of epigenetics follows, in which an unexamined assumption of genetic determinism is debunked. A move to recognize human existence everywhere as contextualized in environments that impinge on body functioning throughout life opens up a discussion of the embodiment of trauma followed by six illustrative examples from the newly recognized field of environmental epigenetics.
“Making Patients” in Postwar and Resource‐scarce Settings. Diagnosing and Treating Mental Illness in Postwar Kosovo
Authors: Kienzler Hanna 
Published: April 2020

AbstractPostwar development contexts are increasingly sites of mental health and psychosocial interventions in which local health providers are trained by foreign experts in evidence‐based diagnostic and treatment strategies. Underlying this course of action is a well‐accepted biomedical logic that assumes symptoms can be identified and translated into mental disorders, and disorders into forms of treatment. I question this logic by investigating how patients are actually “made” in postwar and resource‐scarce settings. Specifically, I focus on the tensions and ethical dilemmas with which practitioners in Kosovo grapple as they navigate requirements of international standards, their own perception of good care, and the limited resources at their disposal. The resultant practice of “making patients” to fit diagnostic repertoires is a product of health practitioners’ structural power, but also an ethical response to the materially untenable conditions that practitioners and their patients are confronting.
Primary papillary epithelial tumour of the sella: expanding the spectrum of TTF‐1‐positive sellar lesions
Authors: Roncaroli F. , Chatterjee D. , Giannini C. , Pereira M. , La Rosa S. , Brouland J. P. , Gnanalingham K. , Galli C. , Fernandes B. , Lania A. , Radotra B. 
Published: April 2020

AimTo describe four novel primary epithelial tumours of the sella with papillary architecture and Thyroid Transcription Factor 1 (TTF‐1) expression.MethodsParaffin‐embedded tissue from the four cases and recurrence of patient 1 was investigated with haematoxylin–eosin, special histochemical stains, immunohistochemistry with a broad panel of antibodies and next‐generation sequencing. The ultrastructure of one tumour was studied in tissue retrieved from paraffin.ResultsThe lesions occurred in three females aged 20, 26 and 42 years and a male aged 49 years. They presented with signs and symptoms secondary to pituitary stalk compression. Preoperative neuroimaging documented mixed solid and cystic, enhancing sellar masses with suprasellar extension. Histologically, the tumours showed thin papillae lined by a single layer of cytokeratin and TTF‐1‐positive cuboidal and cylindrical cells with mildly atypical nucleus. Next‐generation sequencing performed in three cases did not identify any mutations. The main differential diagnosis included metastasis from lung or thyroid carcinoma, extraventricular choroid plexus papilloma and sellar ependymoma.ConclusionWe suggest the descriptive term of primary papillary epithelial tumour of the sella (PPETS) for this entity and propose that it could represent the intracranial equivalent of thyroid‐like low‐grade nasopharyngeal papillary adenocarcinoma. The cell of origin of PPETS remains undetermined although the intense and ubiquitous expression of TTF‐1 may suggest a derivation from the infundibulum or ventricular recess. Our study expands the spectrum of sellar TTF‐1‐positive tumour and challenges the view that they all derive from pituicytes.
Interventions for caregivers of children with food allergy: A systematic review
Authors: Sugunasingha Naomi , Jones Fergal W. , Jones Christina J. 
Published: April 2020

AbstractBackgroundStudies have identified that food allergy (FA) in children is related to poorer caregiver quality of life (QoL). However, it is unclear which interventions are most effective at improving outcomes for caregivers of children with FA. This review aimed to identify and determine the efficacy, acceptability and quality of interventions for caregivers of children with FA.MethodsA systematic search of four databases was conducted to identify studies evaluating any intervention that targeted well‐being and support of caregivers of children with FA. Studies were not excluded based on design and were rated for quality using the Mixed Methods Appraisal Tool (MMAT) and the Cochrane risk of bias tool for randomized controlled trials (RCTs).ResultsFifteen studies met the inclusion criteria: eight studies used a pre‐test/post‐test design, four studies used a post‐test design, two studies used an RCT design, and one study used a case‐control design. Seven studies were educational interventions, five were psychological interventions, and three involved peer/professional support. All interventions had high participant acceptability; some evidence for cognitive behavioural interventions in supporting mothers was observed. Educational interventions tended to be associated with improvements in FA knowledge. With the exception of three studies, most studies were assessed as poor or moderate in terms of quality.ConclusionThere is a paucity of high‐quality research evaluating interventions to improve outcomes in parents of children with FA. Limited evidence suggests that cognitive behavioural interventions could benefit some mothers, but this has not been tested in other populations. Future research should use methodologically sound designs with validated outcome measures.
Predicting no-shows in paediatric orthopaedic clinics
Authors: Robaina Joey A , Bastrom Tracey P , Richardson Andrew C , Edmonds Eric W 
Published: April 2020

BackgroundClinic ‘no shows’ (NS) can be a burden on the healthcare system, and efforts to minimise them can reduce lost revenue and improve patient care. Leveraging a large data set via the electronic health record (EHR) has not been previously attempted to identify ‘high risk’ groups in paediatric orthopaedics.ObjectiveTo use discrete data captured by the EHR system to identify predictors of non-attendance at paediatric orthopaedic outpatient appointments.MethodsAppointments from January 2014 to March 2016 were included. Variables included appointment status, age, gender, type of visit, payor type (government vs private insurance), distance of residence to clinic, region of residence, clinic location, clinic type, and appointment day of the week, hour and month. Classification and regression trees (CART) were constructed to identify predictors of NS.Results131 512 encounters were included, 15 543 of which were in the NS group (11.8%). CART identified three predictive covariates for NS: days in between scheduling and appointment, insurance type, and specific orthopaedic clinic type. The combination of covariates provided predictability of NS: if they had ≤38.5 days of waiting for appointment and had private insurance, the NS rate was 7.8% (the best result), compared with waiting >38.5 days for either a fracture or sports clinic, which had an NS rate of 29.3% (OR=4.9).ConclusionPayor type and duration between scheduling and appointment may predict non-attendance at outpatient paediatric orthopaedic appointments. Although these findings allow for predicting and interventions for at-risk groups, even the best performing NS group occurred 7.8% of the time, highlighting the complexity of the NS phenomenon.
Lay of the land: narrative synthesis of tackle research in rugby union and rugby sevens
Authors: Burger Nicholas , Lambert Mike , Hendricks Sharief 
Published: April 2020

Objectives
The purpose of this review was to synthesise both injury prevention and performance tackle-related research to provide rugby stakeholders with information on tackle injury epidemiology, including tackle injury risk factors and performance determinants, and to discuss potential preventative measures.

Design
Systematic review and narrative synthesis.

Data sources
PubMed, Scopus and Web of Science.

Eligibility criteria
Limited to peer-reviewed English-only publications between January 1995 and October 2018.

Results
A total of 317 studies were identified, with 177 in rugby union and 13 were in rugby sevens. The tackle accounted for more than 50% of all injuries in rugby union and rugby sevens, both at the professional level and at the lower levels, with the rate of tackle injuries higher at the professional level (mean 32/1000 player-hours) compared with the lower levels (mean 17/1000 player-hours). A player’s tackle actions and technical ability were identified as major risk factors for injury and a key determinant of performance.

Summary/conclusion
Evidence-based education, progressive tackle technique training with a high potential to transfer and law changes have been proposed as key modifiers of player tackle actions and technical ability. Conceivably, all three modifiers working in unison (as opposed to separately) will have a higher potential at reducing tackle injury risk while enhancing performance. With the guidance of tackle injury and performance studies, as well as stakeholder engagement, experiential and explorative tackle research has the potential to inspire innovative injury prevention and performance strategies.
Cancer cell-intrinsic expression of MHC II in lung cancer cell lines is actively restricted by MEK/ERK signaling and epigenetic mechanisms
Authors: Neuwelt Alexander J , Kimball Abigail K , Johnson Amber M , Arnold Benjamin W , Bullock Bonnie L , Kaspar Rachael E , Kleczko Emily K , Kwak Jeff W , Wu Meng-Han , Heasley Lynn E , Doebele Robert C , Li Howard Y , Nemenoff Raphael A , Clambey Eric T 
Published: April 2020

BackgroundProgrammed death 1/programmed death ligand 1 (PD-1/PD-L1) targeted immunotherapy affords clinical benefit in ~20% of unselected patients with lung cancer. The factor(s) that determine whether a tumor responds or fails to respond to immunotherapy remains an active area of investigation. We have previously defined divergent responsiveness of two KRAS-mutant cell lines to PD-1/PD-L1 blockade using an orthotopic, immunocompetent mouse model. Responsiveness to PD-1/PD-L1 checkpoint blockade correlates with an interferon gamma (IFNγ)-inducible gene signature and major histocompatibility complex class II (MHC II) expression by cancer cells. In the current study, we aim to identify therapeutic targets that can be manipulated in order to enhance cancer-cell-specific MHC II expression.MethodsResponsiveness to IFNγ and induction of MHC II expression was assessed after various treatment conditions in mouse and human non-small cell lung cancer (NSCLC) cell lines using mass cytometric and flow cytometric analysis.ResultsSingle-cell analysis using mass and flow cytometry demonstrated that IFNγ consistently induced PD-L1 and MHC class I (MHC I) across multiple murine and human NSCLC cell lines. In contrast, MHC II showed highly variable induction following IFNγ treatment both between lines and within lines. In mouse models of NSCLC, MHC II induction was inversely correlated with basal levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting potential mitogen-activated protein (MAP) kinase-dependent antagonism of MHC II expression. To test this, cell lines were subjected to varying levels of stimulation with IFNγ, and assessed for MHC II expression in the presence or absence of mitogen-activated protein kinase kinase (MEK) inhibitors. IFNγ treatment in the presence of MEK inhibitors significantly enhanced MHC II induction across multiple lung cancer lines, with minimal impact on expression of either PD-L1 or MHC I. Inhibition of histone deacetylases (HDACs) also enhanced MHC II expression to a more modest extent. Combined MEK and HDAC inhibition led to greater MHC II expression than either treatment alone.ConclusionsThese studies emphasize the active inhibitory role that epigenetic and ERK signaling cascades have in restricting cancer cell-intrinsic MHC II expression in NSCLC, and suggest that combinatorial blockade of these pathways may engender new responsiveness to checkpoint therapies.
‘Being politically active does not have to be difficult.’ A content analysis of tobacco industry-sponsored advocacy websites
Authors: Lewis M Jane , Ackerman Christopher , Ling Pamela 
Published: April 2020

ObjectiveTo characterise the thematic content of tobacco industry-sponsored advocacy websites in the USA and to compare these sites to identify differences in products, target audience, policies or themes.MethodsIn 2017, US-based Google and purposive searches identified six US tobacco industry-sponsored advocacy websites. A coding guide based on existing literature, tobacco policy issues and iterative review of the websites was developed and, descriptive analyses of themes on individual websites and overall were conducted.ResultsWe identified 18 themes; the most common of these were: tobacco taxes (13.9%), providing advocacy resources (10.6%) and pleas for action (10.3%). Related themes were aggregated into four broad categories: advocacy (36.7%), taxes (31.4%), legislation is excessive or unnecessary (21%), and support for weaker tobacco control policies (10.9%). Websites targeting consumers provided more resources to facilitate advocacy than websites targeting retailers.ConclusionsWebsites promoting protobacco advocacy are an important and evolving strategy for the tobacco industry. Websites are particularly well suited to leverage marketing activities (eg, building relationships with retailers and consumers) to achieve policy objectives. Monitoring these tactics may allow advocates to counter and anticipate industry opposition to tobacco policy.
Multidisciplinary Heart Team Approach for Complex Coronary Artery Disease: Single Center Clinical Presentation
Authors: Young Michael N. , Kolte Dhaval , Cadigan Mary E. , Laikhter Elizabeth , Sinclair Kevin , Pomerantsev Eugene , Fifer Michael A. , Sundt Thoralf M. , Yeh Robert W. , Jaffer Farouc A. 
Published: April 2020

Background
The Heart Team approach is ascribed a Class I recommendation in contemporary guidelines for revascularization of complex coronary artery disease. However, limited data are available regarding the decision‐making and outcomes of patients based on this strategy.

Methods and Results

One hundred sixty‐six high‐risk coronary artery disease patients underwent Heart Team evaluation at a single institution between January 2015 and November 2018. We prospectively collected data on demographics, symptoms, Society of Thoracic Surgeons Predicted Risk of Mortality/Synergy Between PCI with Taxus and Cardiac Surgery (
STS
‐
PROM
/
SYNTAX
) scores, mode of revascularization, and outcomes. Mean age was 70.0 years; 122 (73.5%) patients were male. Prevalent comorbidities included diabetes mellitus (51.8%), peripheral artery disease (38.6%), atrial fibrillation (27.1%), end‐stage renal disease on dialysis (13.3%), and chronic obstructive pulmonary disease (21.7%). Eighty‐seven (52.4%) patients had New York Heart Association
III
‐
IV
and 112 (67.5%) had Canadian Cardiovascular Society
III
‐
IV
symptomatology. Sixty‐seven (40.4%) patients had left main and 118 (71.1%) had 3‐vessel coronary artery disease. The median
STS
‐
PROM
was 3.6% (interquartile range 1.9, 8.0) and
SYNTAX
score was 26 (interquartile range 20, 34). The median number of physicians per Heart Team meeting was 6 (interquartile range 5, 8). Seventy‐nine (47.6%) and 49 (29.5%) patients underwent percutaneous coronary intervention and coronary artery bypass grafting, respectively. With increasing
STS
‐
PROM
(low, intermediate, high operative risk), coronary artery bypass graft was performed less often (47.9%, 18.5%, 15.2%) and optimal medical therapy was recommended more often (11.3%, 18.5%, 30.3%). There were no trends in recommendation for coronary artery bypass graft, percutaneous coronary intervention, or optimal medical therapy by
SYNTAX
score tertiles. In‐hospital and 30‐day mortality was 3.9% and 4.8%, respectively.

Conclusions
Integrating a multidisciplinary Heart Team into institutional practice is feasible and provides a formalized approach to evaluating complex coronary artery disease patients. The comprehensive assessment of surgical, anatomical, and other risk scores using a decision aid may guide appropriate, evidence‐based management within this team‐based construct.
Whole‐Genome Approach Discovers Novel Genetic and Nongenetic Variance Components Modulated by Lifestyle for Cardiovascular Health
Authors: Zhou Xuan , van der Werf Julius , Carson‐Chahhoud Kristin , Ni Guiyan , McGrath John , Hyppönen Elina , Lee S. Hong 
Published: April 2020

Background
Both genetic and nongenetic factors can predispose individuals to cardiovascular risk. Finding ways to alter these predispositions is important for cardiovascular disease prevention.

Methods and Results
We used a novel whole‐genome approach to estimate the genetic and nongenetic effects on—and hence their predispositions to—cardiovascular risk and determined whether they vary with respect to lifestyle factors such as physical activity, smoking, alcohol consumption, and dietary intake. We performed analyses on the ARIC (Atherosclerosis Risk in Communities) Study (N=6896–7180) and validated findings using the UKBB (UK Biobank, N=14 076–34 538). Lifestyle modulation was evident for many cardiovascular traits such as body mass index and resting heart rate. For example, alcohol consumption modulated both genetic and nongenetic effects on body mass index, whereas smoking modulated nongenetic effects on heart rate, pulse pressure, and white blood cell count. We also stratified individuals according to estimated genetic and nongenetic effects that are modulated by lifestyle factors and showed distinct phenotype–lifestyle relationships across the stratified groups. Finally, we showed that neglecting lifestyle modulations of cardiovascular traits would on average reduce single nucleotide polymorphism heritability estimates of these traits by a small yet significant amount, primarily owing to the overestimation of residual variance.

Conclusions
Lifestyle changes are relevant to cardiovascular disease prevention. Individual differences in the genetic and nongenetic effects that are modulated by lifestyle factors, as shown by the stratified group analyses, implies a need for personalized lifestyle interventions. In addition, single nucleotide polymorphism–based heritability of cardiovascular traits without accounting for lifestyle modulations could be underestimated.