bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of socioeconomic deprivation as determined by the English deprivation deciles on the progression of diabetic retinopathy and maculopathy: a multivariate case–control analysis of 88 910 patients attending a South-East London diabetic eye screening service
Authors: Giannakis Periklis , Nderitu Paul , Nunez do Rio Joan M , Webster Laura , Mann Samantha , Hopkins David , Cardoso Manuel Jorge , Modat Marc , Bergeles Christos , Jackson Timothy L 
Published: June 2023

PurposeTo determine associations between deprivation using the Index of Multiple Deprivation (IMD and individual IMD subdomains) with incident referable diabetic retinopathy/maculopathy (termed rDR).MethodsAnonymised demographic and screening data collected by the South-East London Diabetic Eye Screening Programme were extracted from September 2013 to December 2019. Multivariable Cox proportional models were used to explore the association between the IMD, IMD subdomains and rDR.ResultsFrom 118 508 people with diabetes who attended during the study period, 88 910 (75%) were eligible. The mean (± SD) age was 59.6 (±14.7) years; 53.94% were male, 52.58% identified as white, 94.28% had type 2 diabetes and the average duration of diabetes was 5.81 (±6.9) years; rDR occurred in 7113 patients (8.00%). Known risk factors of younger age, Black ethnicity, type 2 diabetes, more severe baseline DR and diabetes duration conferred a higher risk of incident rDR. After adjusting for these known risk factors, the multivariable analysis did not show a significant association between IMD (decile 1 vs decile 10) and rDR (HR: 1.08, 95% CI: 0.87 to 1.34, p=0.511). However, high deprivation (decile 1) in three IMD subdomains was associated with rDR, namely living environment (HR: 1.64, 95% CI: 1.12 to 2.41, p=0.011), education skills (HR: 1.64, 95% CI: 1.12 to 2.41, p=0.011) and income (HR: 1.19, 95% CI: 1.02 to 1.38, p=0.024).ConclusionIMD subdomains allow for the detection of associations between aspects of deprivation and rDR, which may be missed when using the aggregate IMD. The generalisation of these findings outside the UK population requires corroboration internationally.
Differences in acute ischaemic stroke in-hospital mortality across referral stroke hospitals in Spain: a retrospective, longitudinal observational study
Authors: Estupiñán-Romero Francisco , Pinilla Dominguez Jaime , Bernal-Delgado Enrique 
Published: June 2023

ObjectiveTo assess differences in acute ischaemic stroke (AIS) in-hospital mortality between referral stroke hospitals and provide evidence on the association of those differences with the overtime adoption of effective reperfusion therapies.DesignRetrospective, longitudinal observational study using administrative data for virtually all hospital admissions from 2003 to 2015.SettingThirty-seven referral stroke hospitals in the Spanish National Health System.ParticipantsPatients aged 18 years and older with a hospital episode with an admission diagnosis of AIS in any referral stroke hospital (196 099 admissions).Main endpoints(1) Hospital variation in 30-day in-hospital mortality measured in terms of the intraclass correlation coefficient (ICC); and (2) the difference in mortality between the hospital of treatment and the trend of utilisation of reperfusion therapies (including intravenous fibrinolysis and endovascular mechanical thrombectomy) in terms of median OR (MOR).ResultsAdjusted 30-day AIS in-hospital mortality decreased over the study period. Adjusted in-hospital mortality after AIS rates varied from 6.66% to 16.01% between hospitals. Beyond differences in patient characteristics, the relative contribution of the hospital of treatment was higher in the case of patients undergoing reperfusion therapies (ICC=0.031 (95% Bayesian credible interval (BCI)=0.017 to 0.057)) than in the case of those who did not (ICC=0.016 (95% BCI=0.010 to 0.026)). Using the MOR, the difference in risk of death was as high as 46% between the hospital with the highest risk and the hospital with the lowest risk of patients undergoing reperfusion therapy (MOR 1.46 (95% BCI 1.32 to 1.68)); in patients not undergoing any reperfusion therapy, the risk was 31% higher (MOR 1.31 (95% BCI 1.24 to 1.41)).ConclusionsIn the referral stroke hospitals of the Spanish National Health System, the overall adjusted in-hospital mortality decreased between 2003 and 2015. However, between-hospital variations in mortality persisted.
Effect of the COVID-19 pandemic on outpatient care and rehabilitation in neuromuscular clinical practice in Japan: a health insurance claims database analysis
Authors: Saito Toshio , Matsuo-Tezuka Yukari , Sugitani Yasuo , Tajima Takumi , Fukao-Washino Junko , Sakai Sadaoki , Iwagami Masao 
Published: June 2023

ObjectivesTo evaluate the impact of the COVID-19 pandemic on outpatient care in Japanese patients with neuromuscular diseases (NMDs).DesignThis retrospective cohort study included patients between January 2018 and February 2019; the follow-up period was divided into ‘before COVID-19’ (March 2019–February 2020) and ‘during COVID-19’ (March 2020–February 2021).SettingJMDC claims database study.ParticipantsOf the 10 655 557 patients identified, we included patients with spinal muscular atrophy (SMA; n=82), neuromyelitis optica (NMO; n=342), myasthenia gravis (MG; n=1347), Guillain-Barré syndrome (GBS; n=442) or autoimmune encephalitis/encephalopathy (AIE; n=133). Patients were required to have ≥1 month of data available, have a diagnosis of NMD during the enrolment period and be available for follow-up.Primary and secondary outcome measuresWe estimated the proportion of patients with >30% change in outpatient consultation and rehabilitation visits before versus during the COVID-19 pandemic.ResultsSmall reductions in the proportion of patients with outpatient consultation/rehabilitation visits were observed before versus during the pandemic. Compared with before the pandemic, 30.4%, 27.8%, 28.7%, 49.4% and 50.0% of patients showed a >30% decrease in outpatient consultation visits and 58.6%, 75.0%, 50.0%, 76.3% and 84.6% showed a >30% decrease in outpatient rehabilitation visits during the pandemic for SMA, NMO, MG, GBS and AIE, respectively. The median change in the number of outpatient consultation visits per year before versus during pandemic was −1.0 day for all NMDs, and that in outpatient rehabilitation visits per year was −6.0, –5.5, −1.5, –6.5 and −9.0 days for SMA, NMO, MG, GBS and AIE, respectively. The reduction in outpatient rehabilitation visits was greater in the absence versus presence of a neurology specialist.ConclusionsOutpatient consultation and rehabilitation visits during the COVID-19 pandemic were affected in Japanese patients with NMDs. Longer-term evaluations are required to understand if these reductions in outpatient care would affect patient prognosis.
Home care/outpatient versus hospital admission in mild acute pancreatitis: protocol of a multicentre, randomised controlled trial (PADI_2 trial)
Authors: Ramírez-Maldonado Elena , Rodrigo-Rodrigo Marta , Lopez Gordo Sandra , Sanchez Ariadna , Coronado Llanos Daniel , Sanchez Raquel , Vaz Joao , Fondevila Constantino , Jorba-Martin Rosa 
Published: June 2023

IntroductionAcute pancreatitis (AP) is the third most common gastrointestinal disease resulting in hospital admission, with over 70% of AP admissions being mild cases. In the USA, it costs 2.5 billion dollars annually. The most common standard management of mild AP (MAP) still is hospital admission. Patients with MAP usually achieve complete recovery in less than a week and the severity predictor scales are reliable. The aim of this study will be to compare three different strategies for the management of MAP.Methods/designThis is a randomised, controlled, three-arm multicentre trial. Patients with MAP will be randomly assigned to group A (outpatient), B (home care) or C (hospital admission). The primary endpoint of the trial will be the treatment failure rate of the outpatient/home care management for patients with MAP compared with that of hospitalised patients. The secondary endpoints will be pain relapse, diet intolerance, hospital readmission, hospital length of stay, need for intensive care unit admission, organ failure, complications, costs and patient satisfaction. The general feasibility, safety and quality checks required for high-quality evidence will be adhered to.Ethics and disseminationThe study (version 3.0, 10/2022) has been approved by the Scientific and Research Ethics Committee of the ‘Institut d’Investigació Sanitaria Pere Virgili-IISPV’ (093/2022). This study will provide evidence as to whether outpatient/home care is similar to usual management of AP. The conclusions of this study will be published in an open-access journal.Trial registration numberClinicalTrials.gov Registry (NCT05360797).
Advance care plans for vulnerable and disadvantaged adults: systematic review and narrative synthesis
Authors: Brean Samantha Jane , Recoche Katrina , William Leeroy , Lakhani Ali , Zhong Yaping , Shimoinaba Kaori 
Published: June 2023

BackgroundEvidence suggests that there is a gap in advance care planning (ACP) completion between vulnerable and disadvantaged populations compared with the general population. This review seeks to identify tools, guidelines or frameworks that have been used to support ACP interventions with vulnerable and disadvantaged adult populations as well as their experiences and outcomes with them. The findings will inform practice in ACP programmes.MethodsA systematic search of six databases from 1 January 2010 to 30 March 2022 was conducted to identify original peer-reviewed research that used ACP interventions via tools, guidelines or frameworks with vulnerable and disadvantaged adult populations and reported qualitative findings. A narrative synthesis was conducted.ResultsEighteen studies met the inclusion criteria. Relatives, caregivers or substitute decision-makers were included in eight studies. Settings: hospital outpatient clinics (N=7), community settings (N=7), nursing homes (N=2), prison (N=1) and hospital (N=1). A variety of ACP tools, guidelines or frameworks were identified; however, the facilitator’s skills and approach in delivering the intervention appeared to be as important as the intervention itself. Participants indicated mixed experiences, some positive, some negative and four themes emerged: uncertainty, trust, culture and decision-making behaviour. The most common descriptors relating to these themes were prognosis uncertainty, poor end-of-life communication and the importance of building trust.ConclusionThe findings indicate that ACP communication could be improved. ACP conversations should incorporate a holistic and personalised approach to optimise efficacy. Facilitators should be equipped with the necessary skills, tools and information needed to assist ACP decision-making.
Xi Jinping’s Consolidation of Power at the 20th Party Congress: Implications for Chinese Foreign Policy
Authors: ZHAO SUISHENG 
Published: June 2023

The 20th National Congress of the Chinese Communist Party (CCP) in October 2022 secured Xi Jinping’s third term as General Secretary and secured a team of supporters amid socioeconomic woes and increasingly hostile global circumstances. While leadership matters in all political systems, it matters much more in totalitarian and authoritarian ones. Political leaders in democracies are constrained by electoral cycles, term limits, and approval ratings, but the leaders of the PRC’s single-party system that emphasizes discipline, hierarchy, and democratic centralism operate relatively unchecked by bureaucracy, opposition forces, or public opinion. Its leaders possess the ultimate decision-making authority in national security and strategic policies (Zhao, 2022, p. 5).The consolidation of Xi’s power has far-reaching implications for China’s foreign policy. As a feared, sycophantically revered, and ruthless emperor confident in his country’s military power and economic clout, Xi feels equipped to accomplish his mission of making China great again. He has also inherited a pervasive insecurity of pushback from Western powers that threatens his authoritarian rule. He has therefore upheld the security of the regime beyond Deng Xiaoping and his decades of prioritizing growth. Proactively stifling any opposition to his rule and cracking down on any hint of a “color revolution” at home in connection with foreign forces, Xi has strengthened the military and reorganized the economy in preparation for a possible showdown with the United States. He has required Chinese diplomats to act as “wolf warriors” in diplomatic battles and fight criticisms of the regime even at the cost of escalating international tensions. While his team of supporters has maximized his power to implement his policies, this has also prevented his colleagues from counseling against any mistakes they may anticipate or discover. Intentionally or not, he has minimized opportunities to correct his mistakes and increased the stakes and the risks they present, raising the potential for his country to become embroiled in a foreign adventure of no return.
Dissecting the Mechanisms Underlying the Cytokine Release Syndrome (CRS) Mediated by T-Cell Bispecific Antibodies
Authors: Leclercq-Cohen Gabrielle , Steinhoff Nathalie , Albertí Servera Llucia , Nassiri Sina , Danilin Sabrina , Piccione Emily , Yángüez Emilio , Hüsser Tamara , Herter Sylvia , Schmeing Stephan , Gerber Petra , Schwalie Petra , Sam Johannes , Briner Stefanie , Jenni Sylvia , Bianchi Roberta , Biehl Marlene , Cremasco Floriana , Apostolopoulou Katerina , Haegel Hélène , Klein Christian , Umaña Pablo , Bacac Marina 
Published: June 2023

Abstract

Purpose:
Target-dependent TCB activity can result in the strong and systemic release of cytokines that may develop into cytokine release syndrome (CRS), highlighting the need to understand and prevent this complex clinical syndrome.

Experimental Design:
We explored the cellular and molecular players involved in TCB-mediated cytokine release by single-cell RNA-sequencing of whole blood treated with CD20-TCB together with bulk RNA-sequencing of endothelial cells exposed to TCB-induced cytokine release. We used the in vitro whole blood assay and an in vivo DLBCL model in immunocompetent humanized mice to assess the effects of dexamethasone, anti-TNFα, anti-IL6R, anti-IL1R, and inflammasome inhibition, on TCB-mediated cytokine release and antitumor activity.

Results:
Activated T cells release TNFα, IFNγ, IL2, IL8, and MIP-1β, which rapidly activate monocytes, neutrophils, DCs, and NKs along with surrounding T cells to amplify the cascade further, leading to TNFα, IL8, IL6, IL1β, MCP-1, MIP-1α, MIP-1β, and IP-10 release. Endothelial cells contribute to IL6 and IL1β release and at the same time release several chemokines (MCP-1, IP-10, MIP-1α, and MIP-1β). Dexamethasone and TNFα blockade efficiently reduced CD20-TCB–mediated cytokine release whereas IL6R blockade, inflammasome inhibition, and IL1R blockade induced a less pronounced effect. Dexamethasone, IL6R blockade, IL1R blockade, and the inflammasome inhibitor did not interfere with CD20-TCB activity, in contrast to TNFα blockade, which partially inhibited antitumor activity.

Conclusions:
Our work sheds new light on the cellular and molecular players involved in cytokine release driven by TCBs and provides a rationale for the prevention of CRS in patients treated with TCBs.
See related commentary by Luri-Rey et al., p. 4320
Metronomic Administration of Topotecan Alone and in Combination with Docetaxel Inhibits Epithelial–mesenchymal Transition in Aggressive Variant Prostate Cancers
Authors: Mitra Ghosh Taraswi , Mazumder Suman , Davis Joshua , Yadav Jyoti , Akinpelu Ayuba , Alnaim Ahmed , Kumar Harish , Waliagha Razan , Church Bird Allison E. , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , Mishra Amarjit , Yates Clayton C. , Mitra Amit K. , Arnold Robert D. 
Published: June 2023

Prostate cancer is the second leading cause of noncutaneous cancer-related deaths in American men. Androgen deprivation therapy (ADT), radical prostatectomy, and radiotherapy remain the primary treatment for patients with early-stage prostate cancer (castration-sensitive prostate cancer). Following ADT, many patients ultimately develop metastatic castration-resistant prostate cancer (mCRPC). Standard chemotherapy options for CRPC are docetaxel (DTX) and cabazitaxel, which increase median survival, although the development of resistance is common. Cancer stem-like cells possess mesenchymal phenotypes [epithelial-to-mesenchymal transition (EMT)] and play crucial roles in tumor initiation and progression of mCRPC. We have shown that low-dose continuous administration of topotecan (METRO-TOPO) inhibits prostate cancer growth by interfering with key cancer pathway genes. This study utilized bulk and single-cell or whole-transcriptome analysis [(RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq)], and we observed greater expression of several EMT markers, including Vimentin, hyaluronan synthase-3, S100 calcium binding protein A6, TGFB1, CD44, CD55, and CD109 in European American and African American aggressive variant prostate cancer (AVPC) subtypes—mCRPC, neuroendocrine variant (NEPC), and taxane-resistant. The taxane-resistant gene FSCN1 was also expressed highly in single-cell subclonal populations in mCRPC. Furthermore, metronomic-topotecan single agent and combinations with DTX downregulated these EMT markers as well as CD44+ and CD44+/CD133+ “stem-like” cell populations. A microfluidic chip-based cell invasion assay revealed that METRO-TOPO treatment as a single agent or in combination with DTX was potentially effective against invasive prostate cancer spread. Our RNA-seq and scRNA-seq analysis were supported by in silico and in vitro studies, suggesting METRO-TOPO combined with DTX may inhibit oncogenic progression by reducing cancer stemness in AVPC through the inhibition of EMT markers and multiple oncogenic factors/pathways.Significance:The utilization of metronomic-like dosing regimens of topotecan alone and in combination with DTX resulted in the suppression of makers associated with EMT and stem-like cell populations in AVPC models. The identification of molecular signatures and their potential to serve as novel biomarkers for monitoring treatment efficacy and disease progression response to treatment efficacy and disease progression were achieved using bulk RNA-seq and single-cell-omics methodologies.
Socioeconomic Inequalities in Functional Outcome After Reperfusion-Treated Ischemic Stroke
Authors: Buus Sine Mette Øgendahl , Schmitz Marie Louise , Cordsen Pia , Paaske Johnsen Søren , Andersen Grethe , Simonsen Claus Ziegler 
Published: June 2023

BACKGROUND:
We aimed to investigate whether socioeconomic status (SES) was associated with functional outcome in patients with ischemic stroke treated with reperfusion therapy (intravenous thrombolysis and/or thrombectomy).

METHODS:
This nationwide cohort study included reperfusion-treated patients with ischemic stroke ≥18 years registered in the Danish Stroke Registry between 2015 and 2018. Functional outcome was determined by the modified Rankin Scale score 90 days after stroke. SES was defined by educational attainment, family income, and employment status before stroke. SES data were available from Statistics Denmark and linked on the individual level with data from the Danish Stroke Registry. Uni- and multivariable ordinal logistic regression was performed for each socioeconomic parameter individually (education, income, and employment) to estimate the common odds ratios (cORs) for lower 90-day modified Rankin Scale scores.

RESULTS:
A total of 5666 patients were included. Mean age was 68.7 years (95% CI, 68.3–69.0), and 38.4% were female. Low SES was associated with lower odds for achieving lower 90-day modified Rankin Scale score: Low versus high education, cOR, 0.69 (95% CI, 0.61–0.79), low versus high income, cOR, 0.59 (95% CI, 0.53–0.67), and unemployed versus employed, cOR, 0.70 (95% CI, 0.58–0.83). Inequalities were reduced after adjusting for age, sex, and immigrant status, except for unemployed versus employed patients, adjusted cOR, 0.66 (95% CI, 0.54–0.80). No statistically significant differences remained after adjusting for potentially mediating variables (eg, stroke severity, prestroke modified Rankin Scale, and smoking).

CONCLUSIONS:
Socioeconomic inequalities were observed in functional outcome after reperfusion treated ischemic stroke. In particular, prestroke unemployment was negatively associated with good functional outcome. A more adverse prognostic profile among patients with low SES appeared to explain the majority of these inequalities.
Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring
Authors: Alvarado-Bolaños Alonso , Ayan Diana , Khaw Alexander V. , Mai Lauren M. , Mandzia Jennifer L. , Bogiatzi Chrysi , Mrkobrada Marko , Bres-Bullrich Maria , Fleming Lorraine A. , Lippert Corbin , Fridman Sebastian , Sposato Luciano A. 
Published: June 2023

BACKGROUND:
Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF).

METHODS:
We conducted a retrospective, registry-based, cohort study of consecutive patients with ischemic stroke and TIA included in the London Ontario Stroke Registry between 2018 and 2020, with ECG-detected and PCM-detected AF lasting ≥30 seconds. We quantified PCM-detected AF burden. The primary outcome was recurrent ischemic stroke, ascertained by systematically reviewing all medical records until November 2022. We applied marginal cause–specific Cox proportional hazards models adjusted for qualifying event type (ischemic stroke versus TIA), CHA₂DS₂-VASc score, anticoagulation, left ventricular ejection fraction, left atrial size, and high-sensitivity troponin T to estimate adjusted hazard ratios for recurrent ischemic stroke.

RESULTS:

We included 366 patients with ischemic stroke and TIA with AF, 218 ECG-detected, and 148 PCM-detected. Median PCM duration was 12 (interquartile range, 8.8–14.0) days. Median PCM-detected AF duration was 5.2 (interquartile range, 0.3–33.0) hours, with a burden (total AF duration/total net monitoring duration) of 2.23% (interquartile range, 0.13%–12.25%). Anticoagulation rate at the end of follow-up or at the first event was 83.1%. After a median follow-up of 17 (interquartile range, 5–34) months, recurrent ischemic strokes occurred in 16 patients with ECG-detected AF (13 on anticoagulants) and 2 with PCM-detected AF (both on anticoagulants). Recurrent ischemic stroke rates for ECG-detected and PCM-detected AF groups were 4.05 and 0.72 per 100 patient-years (adjusted hazard ratio, 5.06 [95% CI, 1.13–22.7];
P
=0.034).

CONCLUSIONS:
ECG-detected AF was associated with 5-fold higher adjusted recurrent ischemic stroke risk than PCM-detected AF in a cohort of ischemic stroke and TIA with >80% anticoagulation rate.
Human-Horse Relationships, Horse Welfare, and Abuse in Mexico: A Social Representation Approach
Authors: Monterrubio Carlos , Dashper Katherine , Hernández-Espinosa Rafael 
Published: June 2023

Abstract
Drawing on social representation theory, this study explored horse handlers’ understandings of “good” treatment, abuse, and human-horse relationships in tourism, leisure, and sport events in Mexico to examine the ways in which attitudes toward horse welfare are shaped by both national and cultural discourses and wider norms of the global equestrian community. Based on in-depth interviews, the study revealed that national and subcultural norms of the equestrian social world shape people’s attitudes to what is deemed “good treatment” and what is “abuse.” It suggests the need to understand better how cultural factors shape different people’s attitudes to those standards and look for ways to safeguard horse welfare while valuing local heritage.