bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative outcomes of idiopathic epiretinal membrane associated with foveoschisis
Authors: Lam Marion , Philippakis Elise , Gaudric Alain , Tadayoni Ramin , Couturier Aude 
Published: February 2021

AimsTo analyse the prevalence and postoperative outcomes of a particular form of epiretinal membrane (ERM) with foveoschisis-like stretched hyporeflective spaces in emmetropic eyes.MethodsA retrospective study of all consecutive eyes operated for primary ERM over a 46-month period was conducted. The presence of foveoschisis-like stretched hyporeflective spaces was assessed on the preoperative optical coherence tomography B-scan in all eyes. Highly myopic eyes were excluded. Preoperative and postoperative characteristics of eyes with foveoschisis were compared with those of a control group of 100 consecutive eyes with primary ERM without cystoid spaces.ResultsOf 544 eyes with primary ERM, 17 had foveoschisis, corresponding to a prevalence of 3.1%. After a mean postoperative follow-up of 17.9±10.9 months, the foveoschisis had completely resolved in 76.5% of eyes (n=13/17). In the four eyes (23.5%) with persistent foveoschisis, the remaining hyporeflective cystoid spaces were located exclusively in the inner nuclear layer. The postoperative visual acuity and central macular thickness did not differ between both groups at the final visit. However, an acute postoperative macular oedema occurred in 24% (n=4/17) of cases (vs 3% in the control group; p=0.0084).ConclusionFoveoschisis was found in about 3% of eyes with idiopathic ERM. After peeling, the foveoschisis usually resolves completely with functional outcomes similar to those achieved with other primary ERM. However, this feature was associated with a higher risk of postoperative macular oedema (in 1/4 of cases).
Incidence and determinants of hypophosphatemia in diabetic ketoacidosis: an observational study
Authors: van der Vaart Amarens , Waanders Femke , van Beek André P , Vriesendorp Titia M , Wolffenbuttel B H R , van Dijk Peter R 
Published: February 2021

IntroductionDiabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) characterized by hyperglycemia and metabolic acidosis. Hypophosphatemia in DKA often occurs during hospital admittance for DKA. Literature on the magnitude, determinants and consequences of hypophosphatemia in DKA is scarce. Primary aim of this study was to investigate the incidence and consequences of hypophosphatemia during hospitalisation for DKA.Research design and methodsCohort study among individuals with T1DM who were admitted for DKA between 2005 and 2020 in an academic and a non-academic hospital. Multivariate regression models were performed to investigate determinants of the lowest phosphate during the treatment of DKA.ResultsA total of 127 episodes of DKA among 80 individuals were identified. Age at DKA presentation was 28 (22–46) years, 45% of the cases was female, diabetes duration was 13.2 (8.9–25.5) years with glycosylated hemoglobin levels of 91.9±26.2 mmol/mol. In 9% of all cases, DKA was the first presentation of T1DM. Lowest phosphate levelssreported during the treatment phase were 0.54 (0.32–0.83) mmol/L and hypophosphatemia was present in 74% (62/84). The time to lowest phosphate was 16 (8–23) hours. In multivariate analysis, baseline bicarbonate and hemoglobin at admission were significantly associated with the lowest phosphate level reported. No adverse effects of hypophosphatemia on hospital stay duration, morbidity or mortality were found, even if left untreated.ConclusionsHypophosphatemia during DKA is common and increases with severe acidosis. However, in this study it was not related to adverse outcomes. Although limitations of this retrospective study should be taken into account, the routine and repeated measurement of phosphate levels in DKA could be reconsidered, provided that possible symptoms related to hypophosphatemia are monitored.
Risk of common infections in people with inflammatory bowel disease in primary care: a population-based cohort study
Authors: Irving Peter M , de Lusignan Simon , Tang Daniel , Nijher Monica , Barrett Kevin 
Published: February 2021

ObjectiveTo evaluate the risk of common infections in individuals with inflammatory bowel disease (IBD) [ulcerative colitis and Crohn’s disease] compared with matched controls in a contemporary UK primary care population.DesignMatched cohort analysis (2014–2019) using the Royal College of General Practitioners Research and Surveillance Centre primary care database. Risk of common infections, viral infections and gastrointestinal infections (including a subset of culture-confirmed infections), and predictors of common infections, were evaluated using multivariable Cox proportional hazards models.Results18 829 people with IBD were matched to 73 316 controls. People with IBD were more likely to present to primary care with a common infection over the study period (46% vs 37% of controls). Risks of common infections, viral infections and gastrointestinal infections (including stool culture-confirmed infections) were increased for people with ulcerative colitis and Crohn’s disease compared with matched controls (HR range 1.12–1.83, all p<0.001). Treatment with oral glucocorticoid therapy, immunotherapies and biologic therapy, but not with aminosalicylates, was associated with increased infection risk in people with IBD. Despite mild lymphopenia and neutropenia being more common in people with IBD (18.4% and 1.9%, respectively) than in controls (6.5% and 1.5%, respectively), these factors were not associated with significantly increased infection risk in people with IBD.ConclusionPeople with IBD are more likely to present with a wide range of common infections. Health professionals and people with IBD should remain vigilant for infections, particularly when using systemic corticosteroids, immunotherapies or biologic agents.Trial registration numberClinicaltrials.gov (NCT03836612).
Effects of sleepiness on clinical decision making among paramedic students: a simulated night shift study
Authors: Bartlett Danielle , Hansen Sara , Cruickshank Travis , Rankin Timothy , Zaenker Pauline , Mazzucchelli Gavin , Gaston Matthew , Du Plooy Dirk , Minhaj Zahed , Errey William , Rumble Tyron , Hay Taylor , Miles Alecka , Mills Brennen 
Published: February 2021

ObjectiveParamedics are at the forefront of emergency healthcare. Quick and careful decision making is required to effectively care for their patients; however, excessive sleepiness has the potential to impact on clinical decision making. Studies investigating the effects of night shift work on sleepiness, cognitive function and clinical performance in the prehospital setting are limited. Here, we aimed to determine the extent to which sleepiness is experienced over the course of a simulation-based 13-hour night shift and how this impacts on clinical performance and reaction time.MethodsTwenty-four second year paramedic students undertook a 13-hour night shift simulation study in August 2017. The study consisted of 10 real-to-life clinical scenarios. Sleepiness, perceived workload and motivation were self-reported, and clinical performance graded for each scenario. Reaction time, visual attention and task switching were also evaluated following each block of two scenarios.ResultsThe accuracy of participants’ clinical decision making declined significantly over the 13-hour night shift simulation. This was accompanied by an increase in sleepiness and a steady decline in motivation. Participants performed significantly better on the cognitive flexibility task across the duration of the simulated night shift and no changes were observed on the reaction time task. Perceived workload varied across the course of the night.ConclusionOverall, increased sleepiness and decreased clinical decision making were noted towards the end of the 13-hour simulated night shift. It is unclear the extent to which these results are reflective of practising paramedics who have endured several years of night shift work, however, this could have serious implications for patient outcomes and warrants further investigation.
SARS-CoV-2 infection and adverse events in patients with cancer receiving immune checkpoint inhibitors: an observational prospective study
Authors: Mandala Mario , Lorigan Paul , De Luca Matilde , Bianchetti Andrea , Merelli Barbara , Bettini Anna Cecilia , Bonomi Lucia , Nahm Sharon , Vitale Maria Grazia , Negrini Giorgia , Di Croce Andrea , Ascierto Paolo Antonio , Rulli Eliana , Tondini Carlo Alberto 
Published: February 2021

BackgroundIn ambulatory patients with cancer with asymptomatic or pauci-symptomatic SARS-CoV-2 infection, the safety of targeted therapies (TTs), chemotherapy (CT) or immune checkpoint inhibitors (ICIs) therapy is still unknown.Material and methodsFrom the start of the first epidemic wave of SARS-CoV-2 in Bergamo, Italy, we have prospectively screened all consecutive outpatients who presented for treatment to the Oncology Division of the Papa Giovanni XXIII Hospital, Bergamo for SARS-CoV-2 antigen expression. We identified patients treated with ICIs and compared these to patients with the same cancer subtypes treated with TTs or CT.ResultsBetween March 5 and May 18, 293 consecutive patients (49% melanoma, 34% non-small cell lung cancer, 9% renal cell carcinoma, 8% other) were included in this study: 159 (54%), 50 (17%) and 84 (29%) received ICIs, CT or TTs, respectively. Overall 89 patients (30.0%) were SARS-CoV-2 positive. Mortality of SARS-CoV-2-positive patients was statistically significantly higher compared with SARS-CoV-2 negative patients (8/89 vs 3/204, respectively, Fisher’s exact test p=0.004). All deaths were due to COVID-19. Serious adverse events (SAEs) were more frequent in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative cases (Cochran-Mantel-Haenszel (CMH) test p=0.0008). The incidence of SAEs in SARS-CoV-2 positive compared with SARS-CoV-2 negative patients was similar in ICI and CT patients (17.3% and 3.7% for positive and negative patients in ICIs and 15.4% and 2.7% in CT, Breslow-Day test p=0.891). No COVID-19-related SAEs were observed in the TTs patients.ConclusionsThe incidence of SAEs was higher for SARS-CoV-2-positive patients treated with ICIs and CT, mostly in advanced disease. No SAEs were observed in patients treated with TTs. SAEs were COVID-19 related rather than treatment related. Treatment with ICIs does not appear to significantly increase risk of SAEs compared with CT. This information should be considered when determining treatment options for patients.
Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors
Authors: Zhou Jian-Guo , Donaubauer Anna-Jasmina , Frey Benjamin , Becker Ina , Rutzner Sandra , Eckstein Markus , Sun Roger , Ma Hu , Schubert Philipp , Schweizer Claudia , Fietkau Rainer , Deutsch Eric , Gaipl Udo , Hecht Markus 
Published: February 2021

BackgroundThe predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis.MethodsA total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients’ peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status.ResultsWhole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14highmonocytes, CD8+/PD-1+T cells, plasmacytoid dendritic cells, neutrophils, and CD3+/CD56+/CD16+natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI.ConclusionOur study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood.Trial registration numberNCT03453892.
Game of snakes and ladders: barriers and enablers for aspiring women leaders in healthcare
Authors: Magee Lucia , Penfold Rose 
Published: February 2021

BackgroundWomen comprise over three-quarters of the National Health Service workforce, yet remain underrepresented in senior medical grades, on managerial boards and in senior leadership roles. This is attributed to a wide range of internalised, interpersonal and structural factors.ObjectiveTo explore the experiences of aspiring clinical leaders working with senior female leader colleagues and the perceived impact of these interactions on professional development and future aspirations.MethodsHealthcare professionals, self-identifying as female aspiring clinical leaders, were recruited via email and social media to participate in a focus group or semistructured interview. Interviews were recorded and reviewed and the key enablers, barriers and actions to facilitate opportunities for female clinical leaders in the workplace identified.ResultsParticipants (n=11) had varied experiences of working with senior female colleagues. Reported barriers from existing leaders included ‘Queen Bee’ phenomenon and reticence to talk about barriers faced. Enablers included ‘nudging’ towards opportunities and women leaders sharing challenges they had faced and overcome.ConclusionSupporting women to achieve their leadership potential requires individualised support, role modelling and mentorship, and organisational change to tackle workplace biases and microaggressions. These are crucial to ensuring gender balance across leadership in health and social care.
Periprocedural safety of saccular aneurysm embolization with the Penumbra SMART Coil System: a SMART registry subset analysis
Authors: Starke Robert M , Park Min S , Bellon Richard , Bohnstedt Bradley , Schirmer Clemens M , De Leacy Reade , Fiorella David , Yoo Albert J , Spiotta Alejandro M 
Published: February 2021

BackgroundUsing data from the SMART registry, we report on periprocedural safety of the Penumbra SMART Coil System for endovascular coil embolization of saccular intracranial aneurysms.MethodsThe SMART registry was a prospective, multi-center registry of site standard of care endovascular coiling procedures performed using at least 75% Penumbra SMART Coil, PC400, and/or POD coils. This subset analysis reports on the periprocedural safety outcomes of the saccular intracranial aneurysm cohort. Predictors of rupture/re-rupture or perforation (RRP), thromboembolic complications, and device- or procedure-related adverse events (AEs) were determined in univariate and multivariate analysis.ResultsBetween June 2016 and August 2018, 851 saccular aneurysm patients (31.0%, 264/851 ruptured) were enrolled across 66 North American centers. Clinically significant (ie, a serious adverse event) RRP occurred in 2.0% (17/851) of cases – 1.9% (5/264) for the ruptured cohort and 2.0% (12/587) for the un-ruptured cohort. Clinically significant thromboembolic events occurred in 3.1% (26/851) of cases – 5.3% (14/264) for the ruptured cohort and 2.0% (12/587) for the un-ruptured cohort. Multivariate predictors of periprocedural RRP were increased packing density and adjunctive treatment with a balloon. For periprocedural thromboembolic events, multivariate predictors were bifurcation location and ruptured status. For device- or procedure-related AEs, multivariate predictors were bifurcation location and adjunctive treatment with stent or balloon.ConclusionThe low rates of thromboembolic complications and RRP events demonstrate the adequate safety profile of the SMART Coil System to treat cerebral aneurysms in routine clinical practice.Trial registration numberNCT02729740.
miR-33 Silencing Reprograms the Immune Cell Landscape in Atherosclerotic Plaques
Authors: Afonso Milessa Silva , Sharma Monika , Schlegel Martin , van Solingen Coen , Koelwyn Graeme J. , Shanley Lianne C. , Beckett Lauren , Peled Daniel , Rahman Karishma , Giannarelli Chiara , Li Huilin , Brown Emily J. , Khodadadi-Jamayran Alireza , Fisher Edward A. , Moore Kathryn J. 
Published: February 2021

Rationale:
MicroRNA-33 (miR-33 [post-transcriptionally in the rationale]) post-transcriptionally represses genes involved in lipid metabolism and energy homeostasis. Targeted inhibition of miR-33 increases plasma HDL (high-density lipoprotein) cholesterol and promotes atherosclerosis regression, in part, by enhancing reverse cholesterol transport and dampening plaque inflammation. However, how miR-33 reshapes the immune microenvironment of plaques remains poorly understood.

Objective:
To define how miR-33 inhibition alters the dynamic balance and transcriptional landscape of immune cells in atherosclerotic plaques.

Methods and Results:

We used single-cell RNA-sequencing of aortic CD45
+
cells, combined with immunohistologic, morphometric, and flow cytometric analyses to define the changes in plaque immune cell composition, gene expression, and function following miR-33 inhibition. We report that anti–miR-33 treatment of
Ldlr
–/–
mice with advanced atherosclerosis reduced plaque burden and altered the plaque immune cell landscape by shifting the balance of proatherosclerotic and antiatherosclerotic macrophage and T-cell subsets. By quantifying the kinetic processes that determine plaque macrophage burden, we found that anti–miR-33 reduced levels of circulating monocytes and splenic myeloid progenitors, decreased macrophage proliferation and retention, and promoted macrophage attrition by apoptosis and efferocytotic clearance. Single-cell RNA-sequencing of aortic arch plaques showed that anti–miR-33 reduced the frequency of MHCII
hi
(major histocompatibility complex II) inflammatory and Trem2
hi
(Triggering Receptor Expressed On Myeloid Cells 2) metabolic macrophages, but not tissue-resident macrophages. Furthermore, anti–miR-33 led to derepression of distinct miR-33 target genes in the different macrophage subsets: in resident and Trem2
hi
macrophages, anti–miR-33 relieved repression of miR-33 target genes involved in lipid metabolism (eg,
Abca1
,
Ncoa1, Ncoa2
,
Crot
), whereas in MHCII
hi
macrophages, anti–miR-33 upregulated target genes involved in chromatin remodeling and transcriptional regulation. Anti–miR-33 also reduced the accumulation of aortic CD8+ T cells and CD4+ T-helper 1 cells, and increased levels of FoxP3+ (Forkhead Box P3) regulatory T cells in plaques, consistent with an immune-dampening effect on plaque inflammation.

Conclusions:
Our results provide insight into the immune mechanisms and cellular players that execute anti–miR-33’s atheroprotective actions in the plaque.
Loss of CASK Accelerates Heart Failure Development
Authors: Mustroph Julian , Sag Can M. , Bähr Felix , Schmidtmann Anna-Lena , Gupta Shamindra N. , Dietz Alexander , Islam M.M. Towhidul , Lücht Charlotte , Beuthner Bo Eric , Pabel Steffen , Baier Maria J. , El-Armouche Ali , Sossalla Samuel , Anderson Mark E. , Möllmann Julia , Lehrke Michael , Marx Nikolaus , Mohler Peter J. , Bers Donald M. , Unsöld Bernhard , He Tao , Dewenter Matthias , Backs Johannes , Maier Lars S. , Wagner Stefan 
Published: February 2021

Rationale:

Increased myocardial activity of CaMKII (Ca/calmodulin-dependent kinase II) leads to heart failure and arrhythmias. In
Drosophila
neurons, interaction of CaMKII with CASK (Ca/CaM-dependent serine protein kinase) has been shown to inhibit CaMKII activity, but the consequences of this regulation for heart failure and ventricular arrhythmias are unknown.

Objective:
We hypothesize that CASK associates with CaMKII in human and mouse hearts thereby limiting CaMKII activity and that altering CASK expression in mice changes CaMKII activity accordingly, with functional consequences for contractile function and arrhythmias.

Methods and Results:
Immunoprecipitation revealed that CASK associates with CaMKII in human hearts. CASK expression is unaltered in heart failure but increased in patients with aortic stenosis. In mice, cardiomyocyte-specific knockout of CASK increased CaMKII-autophosphorylation at the stimulatory T287 site, but reduced phosphorylation at the inhibitory T305/306 site. Knockout of CASK mice showed increased CaMKII-dependent sarcoplasmic reticulum Ca leak, reduced sarcoplasmic reticulum Ca content, increased susceptibility to ventricular arrhythmias, greater loss of ejection fraction, and increased mortality after transverse aortic constriction. Intriguingly, stimulation of the cardiac glucagon-like peptide 1 receptor with exenatide increased CASK expression resulting in increased inhibitory CaMKII T305 phosphorylation, reduced CaMKII activity, and reduced sarcoplasmic reticulum Ca leak in wild type but not CASK-KO.

Conclusions:
CASK associates with CaMKII in the human heart. Knockout of CASK in mice increases CaMKII activity, leading to contractile dysfunction and arrhythmias. Increasing CASK expression reduces CaMKII activity, improves Ca handling and contractile function.
The Documents Classic as Guide to Political Philosophy in the Early Empires
Authors: Nylan Michael 
Published: February 2021

Abstract
This essay provides an overview of the prescriptions advanced by the Han-era Documents classic, since it was indisputably the Documents that served as the chief guide to political philosophy in the early empires for members of the elite with the requisite high cultural learning. It presents the authoritative pronouncements of the Documents on a number of key issues, such as, Who has the legitimacy to rule? How shall the good ruler and his officials act to retain legitimacy? What is the best form of government? How are punishments to be applied? How are taxes and tribute, domestic and foreign policy, to be administered? It prescribes actions to further the virtues of foresightedness, compassion, and fairness.