bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends in heart failure medication prescription in a population-based cohort study
Authors: Uijl Alicia , Vaartjes Ilonca , Denaxas S , Hemingway Harry , Shah Anoop , Cleland J , Grobbee Diederick , Hoes Arno , Asselbergs Folkert W , Koudstaal Stefan 
Published: March 2021

ObjectiveWe examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).MethodsFrom primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2–85.7) years, with age at diagnosis increasing over time.ResultsWe found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002–2005 and 54% in 2013–2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002–2005 and 18% in 2013–2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.ConclusionIn the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.
Personal protective equipment for reducing the risk of COVID-19 infection among healthcare workers involved in emergency trauma surgery during the pandemic: an umbrella review protocol
Authors: Griswold Dylan P , Gempeler Andres , Kolias Angelos G , Hutchinson Peter J , Rubiano Andres M 
Published: March 2021

IntroductionMany healthcare facilities in low-income and middle-income countries are inadequately resourced and may lack optimal organisation and governance, especially concerning surgical health systems. COVID-19 has the potential to decimate these already strained surgical healthcare services unless health systems take stringent measures to protect healthcare workers (HCWs) from viral exposure and ensure the continuity of specialised care for patients. The objective of this broad evidence synthesis is to identify and summarise the available literature regarding the efficacy of different personal protective equipment (PPE) in reducing the risk of COVID-19 infection in health personnel caring for patients undergoing trauma surgery in low-resource environments.MethodsWe will conduct several searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs automated regular searches in PubMed, Embase, Cochrane Central Register of Controlled Trials and over 30 other sources. The search results will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. This review will preferentially consider systematic reviews of experimental and quasi-experimental studies, as well as individual studies of such designs, evaluating the effect of different PPE on the risk of COVID-19 infection in HCWs involved in emergency trauma surgery. Critical appraisal of eligible studies for methodological quality will be conducted. Data will be extracted using the standardised data extraction tool in Covidence. Studies will, when possible, be pooled in a statistical meta-analysis using JBI SUMARI. The Grading of Recommendations, Assessment, Development and Evaluation approach for grading the certainty of evidence will be followed and a summary of findings will be created.Ethics and disseminationEthical approval is not required for this review. The plan for dissemination is to publish review findings in a peer-reviewed journal and present findings at high-level conferences that engage the most pertinent stakeholders.PROSPERO registration numberCRD42020198267.
Changes in gastric mucosal microbiota in gastric carcinogenesis: a systematic review protocol
Authors: Ji Ruoyu , Zhao Xinyu , Cao Xinyuan , Zhang Yizhen , Yang Yingyun 
Published: March 2021

IntroductionThe human stomach is a complex and diverse microbial ecosystem. Consecutive alternations of gastric microbiota occur in gastric carcinogenesis, while the changing pattern during this process remains controversial across studies. We aim to identify the changes in the diversity and composition of gastric mucosal microbiota in gastric tumorigenesis.Methods and analysisWe will search through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles for observational articles reporting either the relative abundance of bacteria at the phylum or genus level or at least one of the alpha diversity indexes respectively and clearly in both gastric cancer and non-cancer groups. Selection of studies and data extraction will be performed independently by two researchers. Disagreements will be resolved through discussion. Risk of bias will be assessed using the modified Newcastle-Ottawa Scale. Quantitative analyses will be performed using a random effects model, where the effect measurement will be expressed as the MD.Ethics and disseminationEthical approval for this systematic review is not required, as the study is based exclusively on published documents and will not include any individual data. Findings of this study are expected to be disseminated through peer-reviewed journals or conference proceedings.PROSPERO registration numberCRD42020206973.
Multicentre stepped-wedge cluster randomised controlled trial of an antimicrobial stewardship programme in residential aged care: protocol for the START trial
Authors: Jokanovic Natali , Haines Terry , Cheng Allen C , Holt Kathryn E , Hilmer Sarah N , Jeon Yun-Hee , Stewardson Andrew J , Stuart Rhonda L , Spelman Tim , Peel Trisha N , Peleg Anton Y 
Published: March 2021

IntroductionAntimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs.Methods and analysisThe START trial will implement and evaluate a nurse-led AMS programme via a stepped-wedge cluster randomised controlled trial design in 12 RACFs over 16 months. The AMS programme will incorporate education, aged care-specific treatment guidelines, documentation forms, and audit and feedback strategies that will target aged care staff, general practitioners, pharmacists, and residents and their families. The intervention will primarily focus on urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections. RACFs will transition from control to intervention phases in random order, two at a time, every 2 months, with a 2-month transition, wash-in period. The primary outcome is the cumulative proportion of residents within each facility prescribed an antibiotic during each month and total days of antibiotic use per 1000 occupied bed days. Secondary outcomes include the number of courses of systemic antimicrobial therapy, antimicrobial appropriateness, antimicrobial resistant organisms,Clostridioides difficileinfection, change in antimicrobial susceptibility profiles, hospitalisations and all-cause mortality. Analyses will be conducted according to the intention-to-treat principle.Ethics and disseminationEthics approval has been granted by the Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/591). Research findings will be disseminated through peer-reviewed publications, conferences and summarised reports provided to participating RACFs.Trial registration numberNCT03941509.
Tumor-derived ILT4 induces T cell senescence and suppresses tumor immunity
Authors: Gao Aiqin , Liu Xia , Lin Wenli , Wang Jingnan , Wang Shuyun , Si Fusheng , Huang Lan , Zhao Yangjing , Sun Yuping , Peng Guangyong 
Published: March 2021

BackgroundCurrent immunotherapies including checkpoint blockade therapy have limited success rates in certain types of cancers. Identification of alternative checkpoint molecules for the development of effective strategies for tumor immunotherapy is urgently needed. Immunoglobulin-like transcript 4 (ILT4) is an immunosuppressive molecule expressed in both myeloid innate cells and malignant tumor cells. However, the role of tumor-derived ILT4 in regulating cancer biology and tumor immunity remains unclear.MethodsILT4 expression in tumor cells and patient samples was determined by real-time PCR, flow cytometry, and immunohistochemistry. T cell senescence induced by tumor was evaluated using multiple markers and assays. Moreover, metabolic enzyme and signaling molecule expression and lipid droplets in tumor cells were determined using real-time PCR, western blot and oil red O staining, respectively. Loss-of-function and gain-of-function strategies were used to identify the causative role of ILT4 in tumor-induced T cell senescence. In addition, breast cancer and melanoma mouse tumor models were performed to demonstrate the role of ILT4 as a checkpoint molecule for tumor immunotherapy.ResultsWe reported that ILT4 is highly expressed in human tumor cells and tissues, which is negatively associated with clinical outcomes. Furthermore, tumor-derived ILT4/PIR-B (ILT4 ortholog in mouse) is directly involved in induction of cell senescence in naïve/effector T cells mediated by tumor cells in vitro and in vivo. Mechanistically, ILT4/PIR-B increases fatty acid synthesis and lipid accumulation in tumor cellsviaactivation of MAPK ERK1/2 signaling, resulting in promotion of tumor growth and progression, and induction of effector T cell senescence. In addition, blocking tumor-derived PIR-B can reprogram tumor metabolism, prevent senescence development in tumor-specific T cells, and enhance antitumor immunity in both breast cancer and melanoma mouse models.ConclusionsThese studies identify a novel mechanism responsible for ILT4-mediated immune suppression in the tumor microenvironment, and prove a novel concept of ILT4 as a critical checkpoint molecule for tumor immunotherapy.
CD4 T Cell–Dependent Rejection of Beta-2 Microglobulin Null Mismatch Repair–Deficient Tumors
Authors: Germano Giovanni , Lu Steve , Rospo Giuseppe , Lamba Simona , Rousseau Benoit , Fanelli Sonia , Stenech Denise , Le Dung T. , Hays John , Totaro Maria Grazia , Amodio Vito , Chilà Rosaria , Mondino Anna , Diaz Luis A. , Di Nicolantonio Federica , Bardelli Alberto 
Published: March 2021

AbstractInactivation of beta-2 microglobulin (B2M) is considered a determinant of resistance to immune checkpoint inhibitors (ICPi) in melanoma and lung cancers. In contrast, B2M loss does not appear to affect response to ICPis in mismatch repair–deficient (MMRd) colorectal tumors where biallelic inactivation of B2M is frequently observed. We inactivated B2m in multiple murine MMRd cancer models. Although MMRd cells would not readily grow in immunocompetent mice, MMRd B2m null cells were tumorigenic and regressed when treated with anti–PD-1 and anti-CTLA4. The efficacy of ICPis against MMRd B2m null tumors did not require CD8+ T cells but relied on the presence of CD4+ T cells. Human tumors expressing low levels of B2M display increased intratumoral CD4+ T cells. We conclude that B2M inactivation does not blunt the efficacy of ICPi in MMRd tumors, and we identify a unique role for CD4+ T cells in tumor rejection.Significance:B2M alterations, which impair antigen presentation, occur frequently in microsatellite-unstable colorectal cancers. Although in melanoma and lung cancers B2M loss is a mechanism of resistance to immune checkpoint blockade, we show that MMRd tumors respond to ICPis through CD4+ T-cell activation.This article is highlighted in the In This Issue feature, p. 1601
A Jesuit Utopian Project on Behalf of the Conversos: Fernando de Valdés and the Statutes of Purity of Blood (1632)
Authors: Franco Juan Hernández , Ortega-del-Cerro Pablo 
Published: March 2021

Abstract
In 1632, the Jesuit Father Fernando de Valdés (1584–1642) completed his Memorial para quitar o limitar Estatutos de limpieza. In this treatise, Valdés sought to abolish the statutes of purity of blood and reassess the longstanding division between New and Old Christians. Additionally, the Memorial offers a novel portrait of Castilian conversos. According to Valdés, New Christians were singled out for discrimination, despite their evident virtues as sincere Catholics and faithful subjects. He did not seek to break the existing social order, but rather to offer a profound critique of the Old Christian hegemony. Ultimately, Valdés proposed an essentially utopian model of society built on personal merits and behavior, rather than blood-based and inherited privileges. This article seeks to study this Memorial in the context of the debate about the statutes of purity of blood and as an important element of that debate within the Society of Jesus.
The Jesuit António Vieira on Paul’s Judeo-Gentile Universalism and Jewish Resiliency
Authors: Stuczynski Claude B. 
Published: March 2021

Abstract
This article reassesses António Vieira’s views on New Christians and Jews. Rather than presenting a reductive portrait of Vieira’s philosemitism as merely empathic, positive, and tolerant, I argue that his supportive attitudes included some enduring negative ideas of Jewishness. An analysis of Vieira’s pro-converso and prophetic writings (including his Inquisition trial) show that his more ambivalent and dialectical perceptions were ultimately grounded on a theological-political interpretation of Paul’s Judeo-Gentile universalism.
“Great Respect for Texts”: A Conversation with Joseph A. Munitiz
Authors: Colombo Emanuele 
Published: March 2021

Abstract
Father Joseph A. Munitiz, S.J. is one of the founders of the Series Graeca of the Corpus Christianorum and its sister series, Corpus Christianorum in Translation. Throughout his long career, Munitiz has published extensively on Byzantine literature, and his work had a lasting impact on the development of Byzantine studies. He likes to define himself as an “amateur” of Ignatian studies; however, a substantial part of his work has focused on Ignatius and the Society of Jesus, providing an extraordinary contribution in translating and editing early Jesuit sources. This interview is an outcome of the long-distance conversations Emanuele Colombo had with Father Munitiz in 2020.
Westward-Propagating Rossby Modes in Idealized GCMs
Authors: Zurita-Gotor Pablo , Held Isaac M. 
Published: March 2021

AbstractThis work investigates the characteristics of westward-propagating Rossby modes in idealized global general circulation models. Using a nonlinear smoothing algorithm to estimate the background spectrum and an objective method to extract the spectral peaks, the four leading meridional modes can be identified for each of the first three zonal wavenumbers, with frequencies close to the predictions from the Hough modes obtained by linearizing about a state of rest. Variations in peak amplitude for different modes, both within a simulation and across simulations, may be understood under the assumption that the forcing of the modes scales with the background spectrum. Surface friction affects the amplitude and width of the peaks but both remain finite as friction goes to zero, which implies that some other mechanism, arguably nonlinear, must also contribute to the damping of the modes. Although spectral peaks are also observed for the precipitation field with idealized moist physics, there is no evidence of mode enhancement by the convective heating. Subject to the same friction, the amplitude of the peaks are very similar in the dry and moist models when both are normalized by the background spectra.
Albumin Utilization in Spontaneous Bacterial Peritonitis
Authors: Ebied Alex M. , Rattanasuwan Thakul , Chen Yiqing , Khoury Adonice P. 
Published: March 2021

Background: Albumin has been shown to decrease the incidence of mortality and acute kidney injury (AKI) in patients with spontaneous bacterial peritonitis (SBP). Albumin administration in SBP is recommended within 6 hours of diagnosis and for reserved use in high-risk patients with the following baseline laboratory tests: serum creatinine >1 mg/dL, blood urea nitrogen >30 mg/dL or total bilirubin >4 mg/dL. Objective: We aimed to assess the impact of an albumin order set restricted to high-risk SBP. Methods: A retrospective cohort study was conducted between Jan 1, 2013 to Feb 28, 2018. The albumin order set was implemented on Sep 20, 2016. Patients were included if they were diagnosed with SBP and had an ascitic fluid polymorphonuclear count ≥ 250 cells/mm3. Results: Out of a total of 137 patients reviewed, 88 met the inclusion criteria. The incidence of AKI in the pre-order set and post-order set were 63.93% and 33.33% (p = 0.01), respectively. The incidence of mortality in the pre-order set and post-order set were 36.07% and 7.41% (p = 0.005), respectively. The percentage of patients administered albumin within 6 hours were 24.59% to 40.74% (p = 0.14) in the pre-order set and post-order set, respectively. The percentage of patients who received the recommended albumin dosing regimen ordered was 42.62% vs 96.30% (p < 0.001), in the pre-order set and post-order set, respectively. Conclusion: The albumin order set restricted to high-risk SBP patients significantly reduced the incidence of AKI and mortality, and improved the appropriateness of albumin regimen ordered.
Utility of venous‐to‐arterial carbon dioxide changes to arteriovenous oxygen content ratios in the prognosis of severe sepsis and septic shock: A systematic review and meta‐analysis
Authors: Wang Min , Liu Tianyu , Niu Zheng , Zuo Jingzhi , Qi Dunyi 
Published: March 2021

Background:Sepsis patients with insufficient tissue perfusion and hypoxia should be identified and resuscitated immediately. Recently, venous‐to‐arterial carbon dioxide pressure changes and the arteriovenous oxygen content difference ratio (Pcv‐aCO2/Ca‐vO2) as a predictor of tissue perfusion recovery and poor prognosis.Objectives:Pcv‐aCO2/Ca‐vO2 is a substitute for respiratory entropy, the elevation of which indicates a lack of tissue perfusion. Pcv‐aCO2/Ca‐vO2 can be used as an indicator to predict the prognosis of patients with sepsis or septic shock, but its prognostic value has not been fully evaluated. Here, we have performed a meta‐analysis to assess its predictive value for mortality.Methods:Meta‐analysis of Observational Studies in Epidemiology group guidelines were followed for this meta‐analysis. We searched the comprehensive electronic databases of PubMed, EMBASE, Web of Science, and Cochrane libraries from inception to March 2019, using the terms including “venous‐arterial,” “carbon dioxide,” “Shock, Septic,” and related keywords. The Newcastle‐Ottawa scale was used for quality evaluation of the literature. A meta‐analysis was performed using RevMan 5.3 and Stata 14.0 software to evaluate the effects of Pcv‐aCO2/Ca‐vO2 on short‐term mortality, sequential organ failure assessment, and acute physiology and chronic health evaluation scores in patients with sepsis or septic shock.Results:The final analysis included 13 clinical studies involving a total of 940 subjects. The results of the meta‐analysis showed that non‐surviving patients had higher Pcv‐aCO2/Ca‐vO2 than survivors after fluid resuscitation (standardized mean difference = 0.68, 95% confidence interval = 0.24–1.12) and blood samples taken 6 h after resuscitation showed a greater risk of mortality (risk ratio = 1.89, 95% confidence interval = 1.48–2.41) and sequential organ failure assessment scores (mean difference = 1.58, 95% confidence interval = 0.88–2.28, P < 0.01) in patients with high Pcv‐aCO2/Ca‐vO2. These differences were statistically significant.Conclusion:This meta‐analysis indicates that Pcv‐aCO2/Ca‐vO2 has predictive value for mortality in patients with sepsis or septic shock. Further studies are now required to determine the optimal threshold for predicting sepsis mortality.Prospero Registration:The protocol for this systematic review was registered on PROSPERO (CRD 42019128134).
Factors Associated With Delay in Cleft Surgery at a Tertiary Children’s Hospital in a Major US Metropolitan City
Authors: Stoneburner Jacqueline , Munabi Naikhoba C. O. , Nagengast Eric S. , Williams Madeleine S. , Goel Pedram , Auslander Allyn , Howell Lori K. , Hammoudeh Jeffrey A. , Urata Mark M. , Magee William P. 
Published: March 2021

Objective: To identify factors associated with late cleft repair at a US tertiary children’s hospital. Design: Retrospective study of children with CL/P using Children’s Hospital Los Angeles (CHLA) records. Setting: US tertiary children’s hospital. Patients/Participants: Patients undergoing primary CL or CP repair at CHLA from 2009 to 2018. Main Outcome Measures: Proportion of children who had delayed primary CL repair or CP repair using CHLA and American Cleft Palate-Craniofacial Association (ACPA) guidelines and factors associated with late surgery. Results: In total, 805 patients—503 (62.5%) who had CL repair, 302 (37.5%) CP repair—were included. Using CHLA protocol, 14.3% of patients seeking CL repair had delayed surgery. Delay was significantly associated with female gender, non-Hispanic ethnicity, Spanish primary language, government insurance, bilateral cleft, cleft lip and palate (CLP), and syndromic diagnosis. Using ACPA guidelines, 5.4% had delayed surgery. Female gender and syndromic diagnosis were significantly associated with delay and remained significant after adjustment for confounders in multivariate models. For CP repair, 60.3% of patients had delayed surgery using CHLA protocol. Cleft lip and palate diagnosis, complete cleft, syndromic diagnosis, and longer travel distance were significantly associated with delay. Using ACPA guidelines, 28.5% had delayed surgery; however, significant association with patient variables was not consistently observed. Conclusions: Delay in cleft surgery occurs most often for patients seeking CP repair and is associated with female gender, non-Hispanic ethnicity, Spanish language, government insurance, and bilateral CL, CLP, or syndromic diagnoses. Initiatives should aim to optimize cleft surgery delivery for these subpopulations.