bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-fat diet-induced hyperinsulinemia promotes the development of prostate adenocarcinoma in prostate-specific Pten−/− mice
Authors: Wang Hong , Yan William , Sun Yuhai , Yang Chung S 
Published: January 2022

AbstractMetabolic syndrome (MetS) and its four clinical entities, central obesity, insulin resistance, hypertension and dyslipidemia, are implicated in increasing the risk and mortality of cancer in several organs. However, it is unclear how they are associated with increased risk of prostate cancer. To elucidate the mechanistic link between MetS and prostate carcinogenesis, we characterized the development of MetS and prostate adenocarcinoma in prostate-specific Pten−/− (Ptenp−/−) mice fed a high-fat (HF) diet. We found that male Ptenp−/− mice on an HF diet gained excess body weight and elevated blood glucose, insulin and insulin-like growth factor 1 (IGF1) levels at 20 weeks of age and were obese at 40 weeks. Prostate adenocarcinoma multiplicity at 40 weeks was significantly higher in the mice on an HF diet, suggesting that the HF diet promotes the development of prostate adenocarcinoma. Increased cell proliferation and enhanced AKT activation were found in the prostates of mice on an HF diet. Further transcriptome study revealed that receptor tyrosine kinase regulation, which mediates insulin/IGF1 signaling, was one of the top enriched pathways by HF diet-induced transcriptome changes. Together, our results suggest that HF diet-induced hyperinsulinemia leads to increased activation of insulin/IGF1/AKT signaling in lesioned prostates, promoting the development of adenocarcinoma.
Interleukin 17 receptor E identifies heterogeneous T helper 17 cells in peritoneal fluid of moderate and severe endometriosis patients
Authors: Jiang Yanping , Wang Lu , Peng Yaqin , Qin Jian , Tan Aili , Wang Shujun 
Published: January 2022

Abstract
Endometriosis is a chronic inflammatory disorder resulting in pelvic pain and infertility. The role of T helper 17 (Th17) cells in endometriosis remains elusive. In this study, through detecting CXCR3, CCR4, CCR10, CCR6, interleukin-17 Receptor E (IL-17RE), and CD27, RORγt-and-IL-17A-expressing Th17 cells were distinguished and sorted from peritoneal fluid (PF) of patients with stage III and IV endometriosis. Furthermore, we found that IL-17RE and CD27 were the labels of heterogeneous PF Th17 subsets, i.e. IL-17RE-CD27− subset, IL-17RE+CD27- subset, and IL-17RE+CD27+ subset. The former two subsets expressed higher IL-17A, GM-CSF, and IL-22 and were more proliferative than the latter subset. RNA-Seq analysis on IL-17RE+ Th17 subset and IL-17RE- Th17 subset revealed up-regulation of genes involved in oxidative phosphorylation and electron transport chain in IL-17RE+ Th17 subset relative to IL-17RE− Th17 subset. Consistently, the IL-17RE+ Th17 subset produced more adenosine triphosphate (ATP) and reactive oxygen species (ROS) than IL-17RE− Th17 subset. In conclusion, this study provides a novel method to detect and isolate live PF Th17 cells from endometriosis patients and unveils the functional and metabolic heterogeneity of PF Th17 subsets. Therefore, it sheds light on the elucidation of molecular mechanisms that modulate the function of pathological Th17 cells in endometriosis.
Trends in Treatments for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020 – July 2021
Authors: Abrams Joseph Y , Belay Ermias D , Godfred-Cato Shana , Campbell Angela P , Zambrano Laura D , Kunkel Amber , Miller Allison D , Wu Michael J , Meng Lu , Shah Ami B , Oster Matthew E 
Published: January 2022

Abstract

Background
Multisystem inflammatory syndrome in children (MIS-C) is a novel severe postinfectious condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The purpose of this report is to describe nationwide trends in the evolving clinical management of MIS-C.

Methods
Patients with MIS-C were reported from state and local jurisdictions to the Centers for Disease Control and Prevention’s (CDC’s) MIS-C national surveillance system. Patients’ case reports were reviewed to ensure that they met the CDC MIS-C case definition and had sufficient data for analysis. The prevalence of use of treatments for MIS-C, temporal trends in use of these treatments, and frequency of administration of different treatment combinations were analyzed.

Results
There were 4470 patients meeting the MIS-C case definition with onset dates from 19 February 2020 to 31 July 2021. The proportion of patients admitted to an intensive care unit (ICU) has declined over time, from 78.7% in April 2020 to 57.5% in June 2021 (P = .001). The most common treatments were intravenous immunoglobulin (IVIG), given to 85.6% of patients; steroids (77.7%), and antiplatelet medications (73.7%); use of each of these treatments has increased over time, particularly in patients not requiring admission to an ICU (all P &lt; .001). Older patients and non-Hispanic Black patients were more likely to receive additional modes of therapy including vasoactive medication, noninvasive respiratory support, anticoagulation medication, and intubation/mechanical ventilation.

Conclusions
IVIG, steroids, and antiplatelet medication have become increasingly utilized as standard treatment for MIS-C patients, while the use of other treatments may be contingent on the type and severity of clinical findings.
Impact of Education and Data Feedback on Antibiotic Prescribing for Urinary Tract Infections in the Emergency Department: An Interrupted Time-Series Analysis
Authors: Nys Cara L , Fischer Kristen , Funaro Jason , Shoff Christopher J , Theophanous Rebecca G , Staton Catherine A , Mando-Vandrick Jennifer , Toler Rachel , Shroba Jenny , Turner Nicholas A , Liu Beiyu , Lee Hui Jie , Moehring Rebekah W , Wrenn Rebekah H 
Published: January 2022

Abstract

Background
Urinary tract infections (UTIs) are often misdiagnosed or treated with exceedingly broad-spectrum antibiotics, leading to negative downstream effects. We aimed to implement antimicrobial stewardship (AS) strategies targeting UTI prescribing in the emergency department (ED).

Methods
We conducted a quasi-experimental prospective AS intervention outlining appropriate UTI diagnosis and management across 3 EDs, within an academic and 2 community hospitals, in North Carolina, United States. The study was divided into 3 phases: a baseline period and 2 intervention phases. Phase 1 included introduction of an ED-specific urine antibiogram and UTI guideline, education, and department-specific feedback on UTI diagnosis and antibiotic prescribing. Phase 2 included re-education and provider-specific feedback. Eligible patients included adults with an antibiotic prescription for UTI diagnosed in the ED from 13 November 2018 to 1 March 2021. Admitted patients were excluded. The primary outcome was guideline-concordant antibiotic use, assessed using an interrupted time-series regression analysis with 2-week intervals.

Results
Overall, 8742 distinct patients with 10 426 patient encounters were included. Ninety-two percent of all encounters (n = 9583) were diagnosed with cystitis and 8.1% with pyelonephritis (n = 843). There was an initial 15% increase in guideline-concordant antibiotic prescribing in phase 1 compared with the preintervention period (incidence rate ratio [IRR], 1.15; 95% confidence interval [CI], 1.03–1.29). A significant increase in guideline-concordant prescriptions was seen with every 2-week interval during phase 2 (IRR, 1.03; 95% CI, 1.01–1.04).

Conclusions
This multifaceted AS intervention involving a guideline, education, and provider-specific feedback increased guideline-concordant antibiotic choices for treat-and-release patients in the ED.
Lack of Access to Coronavirus Disease 2019 Vaccines Could Be a Greater Threat than Vaccine Hesitancy in Low-Income and Conflict Nations: The Case of Yemen
Authors: Noushad Mohammed , Al-Awar Mohammed Sadeg , Al-Saqqaf Inas Shakeeb , Nassani Mohammad Zakaria , Alrubaiee Gamil Ghaleb , Rastam Samer 
Published: January 2022

Abstract

Background
Vaccine hesitancy and vaccine inequity are 2 major hurdles toward achieving population immunity to coronavirus disease 2019 (COVID-19). Although several studies have been published on vaccine hesitancy among numerous populations, there is inadequate information on any potential correlation between vaccine acceptance and lack of access to vaccines. Our cross-sectional study in a low-income country aimed to fill this gap.

Methods
We conducted a nation-wide cross-sectional survey among the general population in Yemen, a low-income conflict country. Participants from all provinces in Yemen were included in the study. We evaluated factors that influence agreement to accept a COVID-19 vaccine and any potential correlation between vaccine hesitancy and lack of access to vaccines.

Results
Overall, 50.1% of the 5329 respondents agreed to accept a COVID-19 vaccine. Only 39.9% of participants agreed that they had access to a COVID-19 vaccine, with females indicating lower access than males. Potential determinants of vaccine acceptance included being male, updating self on the development of vaccines against COVID-19, opinion about severity of COVID-19, anxiety about contracting COVID-19, concerns about the safety of COVID-19 vaccines, and lack of access to vaccines.

Conclusions
Our results indicate that the immediate threat in Yemen toward achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy.
Omicron Outbreak at a Private Gathering in the Faroe Islands, Infecting 21 of 33 Triple-Vaccinated Healthcare Workers
Authors: Helmsdal Gunnhild , Hansen Olga Kristina , Møller Lars Fodgaard , Christiansen Debes Hammershaimb , Petersen Maria Skaalum , Kristiansen Marnar Fríðheim 
Published: January 2022

Abstract
There are concerns that the severe acute respiratory syndrome coronavirus 2 Omicron variant evades immune responses due to an unusually high number of mutations on the spike protein. Here, we report a superspreading event of Omicron infections among 21 of 33 triple-vaccinated healthcare workers who attended a private gathering.
China’s Emerging Unilateral Sanctions: Heading towards the Rule of Law?
Authors: Yu Wenjie 
Published: January 2022

Abstract
Although China remains consistent in its stance and practice in unilateral sanctions episodes, its ‘decade of sanctions’ has witnessed some subtle changes—in particular, its endeavour to build a rule-of-law-based unilateral sanctions regime. Both international law and the domestic law of China provide for its unilateral sanctions. It is within the discretion of China to take unilateral sanctions as long as it is not against its obligation under the applicable international law, but its domestic law shows a certain level of insufficiency. The administrative nature of unilateral sanctions decides the core parameter of due process for a rule-of-law-based unilateral sanctions regime, which has its boundaries: the limit of law as a regulatory regime for unilateral sanctions as political instrument and the limit of domestic jurisdiction in terms of extraterritorial application. To upgrade the unilateral sanctions regime according to its own concept of rule of law in foreign relations, China needs to improve the compatibility among current laws and to provide proper remedies.
Ethnicity-dependent performance of the Global Registry of Acute Coronary Events risk score for prediction of non-ST-segment elevation myocardial infarction in-hospital mortality: nationwide cohort study
Authors: Moledina Saadiq M , Kontopantelis Evangelos , Wijeysundera Harindra C , Banerjee Shrilla , Van Spall Harriette G C , Gale Chris P , Shah Benoy N , Mohamed Mohamed O , Weston Clive , Shoaib Ahmad , Mamas Mamas A 
Published: January 2022

Abstract

Aims
The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with the acute coronary syndrome with or without ST-segment elevation. Little is known about its performance at predicting in-hospital mortality for ethnic minority patients.

Methods and results
We identified 326 160 admissions with non-ST-segment elevation myocardial infarction (NSTEMI) in the Myocardial Infarction National Audit Project (MINAP), 2010–17, including White (n = 299 184) and ethnic minorities (excluding White minorities) (n = 26 976). We calculated the GRACE score for in-hospital mortality and assessed ethnic group baseline characteristics by low, intermediate and high risk. The performance of the GRACE risk score was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration (calibration plots). Ethnic minorities presented younger and had increased prevalence of cardiometabolic risk factors in all GRACE risk groups. The GRACE risk score for White [AUC 0.87, 95% confidence interval (CI) 0.86–0.87] and ethnic minority (AUC 0.87, 95% CI 0.86–0.88) patients had good discrimination. However, whilst the GRACE risk model was well calibrated in White patients (expected to observed (E : O) in-hospital death rate ratio 0.99; slope 1.00), it overestimated risk in ethnic minority patients (E : O ratio 1.29; slope: 0.94).

Conclusion
The GRACE risk score provided good discrimination overall for in-hospital mortality, but was not well calibrated and overestimated risk for ethnic minorities with NSTEMI.

Key question
Does the performance of the Global Registry of Acute Coronary Events (GRACE) (v2.0) score in predicting in-hospital mortality for non-ST-segment elevation myocardial infarction (NSTEMI) differ by ethnicity?

Key finding
The GRACE risk score provided good discrimination overall for in-hospital mortality but was not well calibrated and overestimated risk for ethnic minority patients with NSTEMI.

Take-home message
Ethnicity or race should be considered during the development of risk scoring systems. Existing systems can be recalibrated in the population they serve to better address risk.
Targeted proteomics improves cardiovascular risk prediction in secondary prevention
Authors: Nurmohamed Nick S. , Belo Pereira João P. , Hoogeveen Renate M. , Kroon Jeffrey , Kraaijenhof Jordan M. , Waissi Farahnaz , Timmerman Nathalie , Bom Michiel J. , Hoefer Imo E. , Knaapen Paul , Catapano Alberico L. , Koenig Wolfgang , de Kleijn Dominique , Visseren Frank L.J. , Levin Evgeni , Stroes Erik S.G. 
Published: January 2022

Abstract

Aims
Current risk scores do not accurately identify patients at highest risk of recurrent atherosclerotic cardiovascular disease (ASCVD) in need of more intensive therapeutic interventions. Advances in high-throughput plasma proteomics, analysed with machine learning techniques, may offer new opportunities to further improve risk stratification in these patients.

Methods and results
Targeted plasma proteomics was performed in two secondary prevention cohorts: the Second Manifestations of ARTerial disease (SMART) cohort (n = 870) and the Athero-Express cohort (n = 700). The primary outcome was recurrent ASCVD (acute myocardial infarction, ischaemic stroke, and cardiovascular death). Machine learning techniques with extreme gradient boosting were used to construct a protein model in the derivation cohort (SMART), which was validated in the Athero-Express cohort and compared with a clinical risk model. Pathway analysis was performed to identify specific pathways in high and low C-reactive protein (CRP) patient subsets. The protein model outperformed the clinical model in both the derivation cohort [area under the curve (AUC): 0.810 vs. 0.750; P &lt; 0.001] and validation cohort (AUC: 0.801 vs. 0.765; P &lt; 0.001), provided significant net reclassification improvement (0.173 in validation cohort) and was well calibrated. In contrast to a clear interleukin-6 signal in high CRP patients, neutrophil-signalling-related proteins were associated with recurrent ASCVD in low CRP patients.

Conclusion
A proteome-based risk model is superior to a clinical risk model in predicting recurrent ASCVD events. Neutrophil-related pathways were found in low CRP patients, implying the presence of a residual inflammatory risk beyond traditional NLRP3 pathways. The observed net reclassification improvement illustrates the potential of proteomics when incorporated in a tailored therapeutic approach in secondary prevention patients.
Solving the eikonal equation for compressional and shear waves in anisotropic media using peridynamic differential operator
Authors: Bekar Ali Can , Madenci Erdogan , Haghighat Ehsan , Waheed Umair bin , Alkhalifah Tariq 
Published: January 2022

SUMMARY
Traveltimes of compressional (P) and shear (S) waves have proven essential in many earthquake and exploration seismology applications. An accurate and efficient traveltime computation for P and S waves is crucial for the success of these applications. However, solving the eikonal equation with a complex phase velocity field in anisotropic media is challenging. The eikonal equation is a first-order nonlinear hyperbolic partial differential equation. It represents the high-frequency asymptotic approximation of the wave equation. The fast marching and sweeping methods are commonly used due to their efficiency in numerically solving the eikonal equation. However, these methods suffer from numerical inaccuracy in anisotropic media with sharp heterogeneity, irregular surface topography and complex phase velocity fields. This study presents a new method for the solution of the eikonal equation by employing the peridynamic differential operator (PDDO). The PDDO provides the non-local form of the eikonal equation by introducing an internal length parameter (horizon) and a weight function with directional non-locality. The operator is immune to discontinuities in the form of sharp changes in field or model variables and invokes the direction of traveltime in a consistent manner. The weight function controls the strength of association among points within the horizon. Solutions are constructed in a consistent manner without upwind assumptions through simple discretization. The robustness of this approach is established by considering different types of eikonal equations on complex velocity models in anisotropic media. The examples demonstrate its unconditional numerical stability and results compare well with the reference solutions.
Who is paid in pay-for-performance? Inequalities in the distribution of financial bonuses amongst health centres in Zimbabwe
Authors: Kovacs Roxanne , Brown Garrett W , Kadungure Artwell , Kristensen Søren R , Gwati Gwati , Anselmi Laura , Midzi Nicholas , Borghi Josephine 
Published: January 2022

Abstract
Although pay-for-performance (P4P) schemes have been implemented across low- and middle-income countries (LMICs), little is known about their distributional consequences. A key concern is that financial bonuses are primarily captured by providers who are already better able to perform (for example, those in wealthier areas), P4P could exacerbate existing inequalities within the health system. We examine inequalities in the distribution of pay-outs in Zimbabwe’s national P4P scheme (2014–2016) using quantitative data on bonus payments and facility characteristics and findings from a thematic policy review and 28 semi-structured interviews with stakeholders at all system levels. We found that in Zimbabwe, facilities with better baseline access to guidelines, more staff, higher consultation volumes and wealthier and less remote target populations earned significantly higher P4P bonuses throughout the programme. For instance, facilities that were 1 SD above the mean in terms of access to guidelines, earned 90 USD more per quarter than those that were 1 SD below the mean. Differences in bonus pay-outs for facilities that were 1 SD above and below the mean in terms of the number of staff and consultation volumes are even more pronounced at 348 USD and 445 USD per quarter. Similarly, facilities with villages in the poorest wealth quintile in their vicinity earned less than all others—and 752 USD less per quarter than those serving villages in the richest quintile. Qualitative data confirm these findings. Respondents identified facility baseline structural quality, leadership, catchment population size and remoteness as affecting performance in the scheme. Unequal distribution of P4P pay-outs was identified as having negative consequences on staff retention, absenteeism and motivation. Based on our findings and previous work, we provide some guidance to policymakers on how to design more equitable P4P schemes.
Narrowing the gap between marine spatial planning aspirations and realities
Authors: Zuercher Rachel , Motzer Nicole , Magris Rafael A , Flannery Wesley 
Published: January 2022

AbstractMany coastal nations have embraced marine spatial planning (MSP) as a solution to maintaining ecological integrity of marine environments, while ensuring continued provisioning of economic, social, and cultural benefits. However, evidence supporting the idea that plans achieve—or are likely to achieve—these goals is limited. One gap in our understanding stems from questions surrounding the metrics against which MSP success is measured. Evaluation can be based on explicitly stated objectives, or might include metrics corresponding to broad social–ecological goals. This paper compares aspirational MSP goals gleaned from a literature review to the objectives extracted from 50+ finalized and implemented plans to better understand: (1) how well these two groupings align, and (2) in what ways any misalignment may shape MSP evaluation. Findings show that plans prioritize the environment, economy, and governance, while often excluding objectives related to cultural heritage, human well-being, Indigenous rights, human safety, and climate change. Social and cultural objectives have become more prevalent over time, yet overall stated objectives remain distinct from theorized MSP goals. As international efforts aim to expand MSP, narrowing the gap between how it is perceived and how its outcomes are evaluated is critical to better understanding what it is likely to achieve.
Copepod habitat suitability estimates vary among oxygen metrics in Chesapeake Bay
Authors: Pierson James J , Testa Jeremy M , Roman Michael R 
Published: January 2022

AbstractSeasonal deoxygenation in coastal and estuarine systems leads to decreased available habitat for many planktonic organisms. However, the volume of available habitat can be defined in different ways, depending on the oxygen metrics employed. Here, we used monitoring data for water quality to estimate the seasonal and inter-annual variability in habitat for the copepod Acartia tonsa in Chesapeake Bay, defined using three different oxygen metrics: a concentration-based (2 mg l−1) definition of hypoxia, and two partial pressure-based definitions corresponding to limiting oxygen demand (Pcrit), and the minimum requirement for respiration (Pleth). We examined spatial and temporal trends in the oxygen habitat, and compared habitat estimates to zooplankton abundance and distribution and in relation to hydrologically wet, average, and dry years. Pcrit predicted the largest volume of unsuitable deoxygenated habitat over space and time, and dry conditions were associated with a decreased extent of deoxygenated habitat compared to average and wet conditions. No clear relationship between copepod abundance and habitat availability was observed, but the position of peak abundance of A. tonsa correlated to the extent of deoxygenated habitat using Pcrit. Species-specific metrics to describe oxygen habitat may be more useful in understanding the non-lethal impacts of deoxygenation.