bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demographic and socioeconomic patterns in healthcare-seeking behaviour for respiratory symptoms in England: a comparison with non-respiratory symptoms and between three healthcare services
Authors: Morrison Kirsty E , Colón-González Felipe J , Morbey Roger A , Hunter Paul R , Rutter Judith , Stuttard Gareth , de Lusignan Simon , Yeates Alex , Pebody Richard , Smith Gillian , Elliot Alex J , Lake Iain R 
Published: November 2020

ObjectiveThis study will analyse respiratory contacts to three healthcare services that capture more of the community disease burden than acute data sources, such as hospitalisations. The objective is to explore associations between contacts to these services and the patient’s age, gender and deprivation. Results will be compared between healthcare services, and with non-respiratory contacts to explore how contacts differ by service and illness. It is crucial to investigate the sociodemographic patterns in healthcare-seeking behaviour to enable targeted public health interventions.DesignEcological study.SettingSurveillance of respiratory contacts to three healthcare services in England: telehealth helpline (NHS111); general practitioner in-hours (GPIH); and general practitioner out of hours unscheduled care (GPOOH).Participants13 million respiratory contacts to NHS111, GPIH and GPOOH.Outcome measuresRespiratory contacts to NHS111, GPIH and GPOOH, and non-respiratory contacts to NHS111 and GPOOH.ResultsMore respiratory contacts were observed for females, with 1.59, 1.73, and 1.95 times the rate of contacts to NHS111, GPOOH and GPIH, respectively. When compared with 15–44 year olds, there were 37.32, 18.66 and 6.21 times the rate of respiratory contacts to NHS111, GPOOH and GPIH in children <1 year. There were 1.75 and 2.70 times the rate of respiratory contacts in the most deprived areas compared with the least deprived to NHS111 and GPOOH. Elevated respiratory contacts were observed for males <5 years compared with females <5 years. Healthcare-seeking behaviours between respiratory and non-respiratory contacts were similar.ConclusionWhen contacts to services that capture more of the disease burden are explored, the demographic patterns are similar to those described in the literature for acute systems. Comparable results were observed between respiratory and non-respiratory contacts suggesting that when a wider spectrum of disease is explored, sociodemographic factors may be the strongest influencers of healthcare-seeking behaviour.
Added value of assessing medical students’ reflective writings in communication skills training: a longitudinal study in four academic centres
Authors: Ament Giuliani Franco Camila , Franco Renato Soleiman , Cecilio-Fernandes Dario , Severo Milton , Ferreira Maria Amélia , de Carvalho-Filho Marco Antonio 
Published: November 2020

ObjectivesThis study describes the development and implementation of a model to assess students’ communication skills highlighting the use of reflective writing. We aimed to evaluate the usefulness of the students’ reflections in the assessment of communication skills.DesignThird-year and fourth-year medical students enrolled in an elective course on clinical communication skills development were assessed using different assessment methods.Setting and participantsThe communication skills course was offered at four universities (three in Brazil and one in Portugal) and included 69 students.Outcome measuresThe students were assessed by a Multiple-Choice Questionnaire (MCQ), an objective structured clinical examination (OSCE) and reflective writing narratives. The Cronbach’s alpha, dimensionality and the person’s correlation were applied to evaluate the reliability of the assessment methods and their correlations. Reflective witting was assessed by applying the Reflection Evaluation for Enhanced Competencies Tool Rubric (Reflect Score (RS)) to measure reflections’ depth, and the Thematic Score (TS) to map and grade reflections’ themes.ResultsThe Cronbach alpha for the MCQ, OSCE global score, TS and RS were, respectively, 0.697, 0.633, 0.784 and 0.850. The interobserver correlation for the TS and RS were, respectively, 0.907 and 0.816. The assessment of reflection using the TS was significantly correlated with the MCQ (r=0.412; p=0.019), OSCE (0.439; p=0.012) and RS (0.410; p=0.020). The RS did not correlate with the MCQ and OSCE.ConclusionsAssessing reflection through mapping the themes and analysing the depth of reflective writing expands the assessment of communication skills. While the assessment of reflective themes is related to the cognitive and behavioural domains of learning, the reflective depth seems to be a specific competence, not correlated with other assessment methods—possibly a metacognitive domain.
Pharmaceutical management of elderly high-risk patients in perioperative settings (PHAROS): protocol of a pilot sequential intervention study
Authors: Richter Julia , Schönfeld Moritz Sebastian , Langebrake Claudia , Bergelt Corinna , Kriston Levente , Olotu Cynthia , Kiefmann Rainer 
Published: November 2020

IntroductionWith increasing age, the risk of complications after surgery rises in elderly patients. Furthermore, the prevalence of multimorbidity and polypharmacy rises with age, making this elderly population especially vulnerable for drug-related problems and posing an additional risk for postoperative complications. Still, only few studies have concentrated on investigating how medication safety can be improved in these patients. The aim of this pilot study is to examine the impact of a comprehensive intervention (interprofessional systematic medication therapy management) on medication appropriateness in elderly polymedicated, multimorbid patients during hospital stay for elective surgery.Methods and analysisThis pilot study will include a total number of 140 patients. Surgical high-risk patients ≥65 years taking more than five chronic systemic drugs will be recruited consecutively for 9 months in the control group capturing usual care regarding medication history and in-hospital medication therapy management without any study intervention. Recruitment of the intervention group will be conducted for another 9 months. The intervention consists of the following components: an additional medication history by a hospital pharmacist before admission, a subsequent medication review, optimisation of the long-term medication and recommendations to the patient’s general practitioner. A follow-up will be performed 3 months after surgery. As the primary study outcome, medication appropriateness will be measured using the Medication Appropriateness Index.Secondary outcomes are postoperative complications, incidence and frequency of adverse drug reactions and potentially inappropriate medication in the elderly, satisfaction with inpatient and outpatient care, medication reconciliation and health-related quality of life. Multivariable analyses will be used to analyse all quantitative research questions.Ethics and disseminationEthics approval was obtained by the medical ethics committee of the Medical Chamber of Hamburg (study ID: PV5754). Data will be published in peer-reviewed journals and presented at conferences.Trial registration numberThe study is registered at www.drks.de: DRKS00014621.
Safe clinical practice for patients hospitalised in mental health wards during a suicidal crisis: qualitative study of patient experiences
Authors: Berg Siv Hilde , Rørtveit Kristine , Walby Fredrik A. , Aase Karina 
Published: November 2020

AimThe aim of this study was to explore suicidal patients’ experiences of safe clinical practice during hospitalisation in mental health wards. The study was guided by the following research question: How do suicidal patients experience safe clinical practice during hospitalisation in mental health wards?Design, setting and participantsA qualitative design with semistructured individual interviews was applied. Eighteen patients hospitalised with suicidal behaviour in specialised mental health wards for adults at a Norwegian hospital participated in the study. Data were analysed thematically and inductively using qualitative content analysis.ResultsPatients in a suicidal crisis experienced safe clinical care in mental health wards characterised by the following three themes: (1) being recognised as suicidal, (2) receiving tailor-made treatment and (3) being protected by adaptive practice.ConclusionThis study illuminates the experiences of safe clinical practice for patients in a suicidal crisis. The patient group was multifaceted, with variable experiences of how safe clinical practice affected their subjective experience of safety and suicidal behaviour. The finding highlights the importance of embracing personalised activities in all parts of safe clinical practice and to recognise rather than efface patients’ variability in patient safety efforts.
Transformation of the Tanzania medical store department through global fund support: an impact assessment study
Authors: Githendu Patrick , Morrison Linden , Silaa Rosemary , Pothapregada Sai , Asiimwe Sarah , Idris Rafiu , Peterson Tatjana , Davidson Emma , Lesego Abaleng , Mwale Neema , Mwakalobo Sako Mayrick , Bwanakunu Laurean Rugambwa , Achoki Tom 
Published: November 2020

BackgroundThe Tanzania government sought support from The Global Fund to Fight AIDs, Tuberculosis and Malaria to reform its Medical Stores Department, with the aim of improving performance. The study sought to assess the impact of the reforms and document the lessons learnt.MethodsQuantitative and qualitative research methods were applied to assess the impact of the reforms. The quantitative part entailed a review of operational and financial data covering the period before and after the implementation of the reforms. Interrupted time series analysis was used to determine the change in average availability of essential health commodities at health zones. Qualitative data were collected through 41 key informant interviews. Participants were identified through stakeholder mapping, purposive and snowballing sampling techniques and responses were analysed through thematic content analysis.ResultsAvailability of essential health commodities increased significantly by 12.6% (95% CI 9.6% to 15.6%) after the reforms and continued to increase on a monthly basis by 0.2% (95%CI 0.0% to 0.3%) relative to the preintervention trend. Sales increased by 56.6% while the cost of goods sold increased by 88.6% between 2014/2015 and 2017/2018. Surplus income increased by 56.4% between 2014/2015 and 2017/2018 with reductions in rent and fuel expenditure. There was consensus among study participants that the reforms were instrumental in improving performance of the Medical Stores Department.ConclusionPositive results were realised through the reforms. However, despite the progress, there were risks such as the increasing government receivable that could jeopardise the sustainability of the gains. Therefore, multistakeholder efforts are necessary to make progress and expand public health.
Abdominal aortic aneurysm is associated with subarachnoid hemorrhage
Authors: Wilkinson D Andrew , Daou Badih J , Nadel Jeffrey L , Chaudhary Neeraj , Gemmete Joseph J , Thompson Byron Gregory , Pandey Aditya S 
Published: November 2020

BackgroundAlthough intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA) share similar risk factors, little is known about the relationship between them. Previous studies have shown an increased incidence of IA in patients with AAA, though the rate of subarachnoid hemorrhage (SAH) in patients with AAA has not been described.ObjectiveTo use claims data with longitudinal follow-up, to evaluate the incidence of aneurysmal SAH in patients diagnosed with AAA.MethodsWe examined longitudinally linked medical claims data from a large private insurer to determine rates of aneurysmal SAH (aSAH) and secured aSAH (saSAH) in 2004–2014 among patients with previously diagnosed AAA.ResultsWe identified 62 910 patients diagnosed with AAA and compared them 5:1 with age- and sex-matched controls. Both populations were predominantly male (70.9%), with an average age of 70.8 years. Rates of hypertension (69.7% vs 50.6%) and smoking (12.8% vs 4.1%) were higher in the AAA group (p<0.0001) than in controls. Fifty admissions for aSAH were identified in patients with AAA (26/100 000 patient-years, 95% CI 19 to 44) and 115 admissions for aSAH in controls (7/100 000 years, 95% CI 6 to 9), giving an incidence rate ratio (IRR) of 3.6 (95% CI 2.6 to 5.0, p<0.0001) and a comorbidity-adjusted incidence rate ratio (IRR) of 2.8 (95% CI 1.9 to 3.9) for patients with AAA. The incidence of secured aneurysmal SAH was proportionally even higher in patients with AAA, 7 vs 2/100 000 years, IRR 4.5 (95% CI 3.2 to 6.3, p<0.0001).ConclusionSAH rate was elevated in patients with AAA, even after adjustment for comorbidities. Among risk factors evaluated, AAA was the strongest predictor for SAH. The relative contributions of common genetic and environmental risk factors to both diseases should be investigated.
Performance of Radiomics derived morphological features for prediction of aneurysm rupture status
Authors: Ludwig Calvin Gerald , Lauric Alexandra , Malek Justin A , Mulligan Ryan , Malek Adel M 
Published: November 2020

BackgroundMorphological differences between ruptured and unruptured cerebral aneurysms represent a focus of neuroimaging researchfor understanding the mechanisms of aneurysmal rupture. We evaluated the performance of Radiomics derived morphological features, recently proposed for rupture status classification, against automatically measured shape and size features previously established in the literature.Methods353 aneurysms (123 ruptured) from three-dimensional rotational catheter angiography (3DRA) datasets were analyzed. Based on a literature review, 13 Radiomics and 13 established morphological descriptors were automatically extracted per aneurysm, and evaluated for rupture status prediction using univariate and multivariate statistical analysis, yielding an area under the curve (AUC) metric of the receiver operating characteristic.ResultsValidation of overlapping descriptors for size/volume using both methods were highly correlated (p<0.0001,R2=0.99). Univariate analysis selected AspectRatio (p<0.0001, AUC=0.75), Non-sphericity Index (p<0.0001, AUC=0.75), Height/Width (p<0.0001, AUC=0.73), and SizeRatio (p<0.0001, AUC=0.73) as best among established descriptors, and Elongation (p<0.0001, AUC=0.71) and Flatness (p<0.0001, AUC=0.72) among Radiomics features. Radiomics Elongation correlated best with established Height/Width (R2=0.52), whereas Radiomics Flatness correlated best with Ellipticity Index (R2=0.54). Radiomics Sphericity correlated best with Undulation Index (R2=0.65). Best Radiomics performers, Elongation and Flatness, were highly correlated descriptors (p<0.0001,R2=0.75). In multivariate analysis, established descriptors (Height/Width, SizeRatio, Ellipticity Index; AUC=0.79) outperformed Radiomics features (Elongation, Maximum3Ddiameter; AUC=0.75).ConclusionAlthough recently introduced Radiomics analysis for aneurysm shape and size evaluation has the advantage of being an efficient operator independent methodology, it currently offers inferior rupture status discriminant performance compared with established descriptors. Future research is needed to extend the current Radiomics feature set to better capture aneurysm shape information.
Quark and pion condensates at finite isospin density in chiral perturbation theory
Authors: Adhikari Prabal , Andersen Jens O. 
Published: November 2020

AbstractIn this paper, we consider two-flavor QCD at zero temperature and finite isospin chemical potential $$\mu _I$$

μ
I

using a model-independent analysis within chiral perturbation theory at next-to-leading order. We calculate the effective potential, the chiral condensate and the pion condensate in the pion-condensed phase at both zero and nonzero pionic source. We compare our finite pionic source results for the chiral condensate and the pion condensate with recent (2+1)-flavor lattice QCD results. Agreement with lattice results generally improves as one goes from leading order to next-to-leading order.
Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
Authors: Wan Changxin , Keany Matthew P. , Dong Han , Al-Alem Linah F. , Pandya Unnati M. , Lazo Suzan , Boehnke Karsten , Lynch Katherine N. , Xu Rui , Zarrella Dominique T. , Gu Shengqing , Cejas Paloma , Lim Klothilda , Long Henry W. , Elias Kevin M. , Horowitz Neil S. , Feltmate Colleen M. , Muto Michael G. , Worley Michael J. , Berkowitz Ross S. , Matulonis Ursula A. , Nucci Marisa R. , Crum Christopher P. , Rueda Bo R. , Brown Myles , Liu Xiaole Shirley , Hill Sarah J. 
Published: November 2020

Abstract

Immune therapies have had limited efficacy in high-grade serous ovarian cancer (HGSC), as the cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single-cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a unique bispecific anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody compared with monospecific anti-PD-1 or anti-PD-L1 controls. Comparing the functions of these agents across all immune cell types in real time identified key immune checkpoint blockade (ICB) targets that have eluded currently available monospecific therapies. The bispecific antibody induced superior cellular state changes in both T and natural killer (NK) cells. It uniquely induced NK cells to transition from inert to more active and cytotoxic phenotypes, implicating NK cells as a key missing component of the current ICB-induced immune response in HGSC. It also induced a subset of CD8 T cells to transition from naïve to more active and cytotoxic progenitor-exhausted phenotypes post-treatment, revealing the small, previously uncharacterized population of CD8 T cells responding to ICB in HGSC. These state changes were driven partially through bispecific antibody-induced downregulation of the bromodomain-containing protein BRD1. Small-molecule inhibition of BRD1 induced similar state changes in vitro and demonstrated efficacy in vivo, validating the co-culture results. Our results demonstrate that state changes in both NK and a subset of T cells may be critical in inducing an effective anti-tumor immune response and suggest that immune therapies able to induce such cellular state changes, such as BRD1 inhibitors, may have increased efficacy in HGSC.

Significance:
This study indicates that increased efficacy of immune therapies in ovarian cancer is driven by state changes of NK and small subsets of CD8 T cells into active and cytotoxic states.
A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer
Authors: Somarelli Jason A. , Roghani Roham Salman , Moghaddam Ali Sanjari , Thomas Beatrice C. , Rupprecht Gabrielle , Ware Kathryn E. , Altunel Erdem , Mantyh John B. , Kim So Young , McCall Shannon J. , Shen Xiling , Mantyh Christopher R. , Hsu David S. 
Published: November 2020

Abstract
Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new treatments for this deadly disease. To address this need, we developed a precision medicine pipeline that integrates high-throughput chemical screens with matched patient-derived cell lines and patient-derived xenografts (PDX) to identify new treatments for colorectal cancer. High-throughput screens of 2,100 compounds were performed across six low-passage, patient-derived colorectal cancer cell lines. These screens identified the CDK inhibitor drug class among the most effective cytotoxic compounds across six colorectal cancer lines. Among this class, combined targeting of CDK1, 2, and 9 was the most effective, with IC50s ranging from 110 nmol/L to 1.2 μmol/L. Knockdown of CDK9 in the presence of a CDK2 inhibitor (CVT-313) showed that CDK9 knockdown acted synergistically with CDK2 inhibition. Mechanistically, dual CDK2/9 inhibition induced significant G2–M arrest and anaphase catastrophe. Combined CDK2/9 inhibition in vivo synergistically reduced PDX tumor growth. Our precision medicine pipeline provides a robust screening and validation platform to identify promising new cancer therapies. Application of this platform to colorectal cancer pinpointed CDK2/9 dual inhibition as a novel combinatorial therapy to treat colorectal cancer.
Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer
Authors: Li Jinyang , Yuan Salina , Norgard Robert J. , Yan Fangxue , Sun Yu H. , Kim Il-Kyu , Merrell Allyson J. , Sela Yogev , Jiang Yanqing , Bhanu Natarajan V. , Garcia Benjamin A. , Vonderheide Robert H. , Blanco Andrés , Stanger Ben Z. 
Published: November 2020

AbstractAlthough immunotherapy has revolutionized cancer care, patients with pancreatic ductal adenocarcinoma (PDA) rarely respond to these treatments, a failure that is attributed to poor infiltration and activation of T cells in the tumor microenvironment (TME). We performed an in vivo CRISPR screen and identified lysine demethylase 3A (KDM3A) as a potent epigenetic regulator of immunotherapy response in PDA. Mechanistically, KDM3A acts through Krueppel-like factor 5 (KLF5) and SMAD family member 4 (SMAD4) to regulate the expression of the epidermal growth factor receptor (EGFR). Ablation of KDM3A, KLF5, SMAD4, or EGFR in tumor cells altered the immune TME and sensitized tumors to combination immunotherapy, whereas treatment of established tumors with an EGFR inhibitor, erlotinib, prompted a dose-dependent increase in intratumoral T cells. This study defines an epigenetic–transcriptional mechanism by which tumor cells modulate their immune microenvironment and highlights the potential of EGFR inhibitors as immunotherapy sensitizers in PDA.Significance:PDA remains refractory to immunotherapies. Here, we performed an in vivo CRISPR screen and identified an epigenetic–transcriptional network that regulates antitumor immunity by converging on EGFR. Pharmacologic inhibition of EGFR is sufficient to rewire the immune microenvironment. These results offer a readily accessible immunotherapy-sensitizing strategy for PDA.This article is highlighted in the In This Issue feature, p. 521