bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent effects of 15 commonly prescribed drugs on all-cause mortality among US elderly patients with type 2 diabetes mellitus
Authors: Baik Seo H , McDonald Clement J 
Published: April 2020

ObjectiveMost patients with type 2 diabetes mellitus (T2DM) also have hypertension and hyperlipidemia. Consequently, they are taking medications for all three conditions concurrently and the effect of one drug could be confounded with that of another. This study aimed to determine the independent effects of 15 commonly prescribed medications for three conditions on the risk of all-cause mortality among elderly patients with T2DM.Research design and methodsA cohort of 360 437 elderly patients with T2DM from 2007 to 2016 US Medicare data was traced along with cumulative uses of 8 diabetes, 6 hypertension and 1 hyperlipidemia drugs. The relative risk of all-cause mortality for each study drug was estimated using an extended Cox regression analysis adjusting for the concurrent use of other study drugs.ResultsCompared with the no use of each study medication, mortality risk declined with use of 3 diabetes drugs, sodium-glucose cotransporter-2 inhibitors (HR=0.73; 95% CI 0.64 to 0.84), glucagon-like peptide-1 receptor agonists (HR=0.75; 95% CI 0.70 to 0.80) and dipeptidyl peptidase-4 inhibitors (HR=0.94; 95% CI 0.91 to 0.98), the use of 3 blood pressure medications, diuretics (HR=0.89; 95% CI 0.87 to 0.92), angiotensin receptor blockers (HR=0.86; 95% CI 0.84 to 0.89), ACE inhibitors (HR=0.98; 95% CI 0.95 to 1.01) as well as statins (HR=0.83; 95% CI 0.80 to 0.85). It increased moderately with insulin (HR=1.55; 95% CI 1.51 to 1.59), sulfonylureas (HR=1.16; 95% CI 1.13 to 1.20), a smallinconsistentamount with metformin (HR=1.05), beta-blockers (HR=1.07), dihydropyridine calcium-channel blockers (HR=0.99) and non-dihydropyridine calcium-channel blockers (HR=1.05). The use of thiazolidinedione had no effect.ConclusionAmong older patients with diabetes, mortality riskdecreasedimportantly with three new diabetes drugs, 3 blood pressure drugs and statins. Itincreasedmoderately with sulfonylurea and insulin. Studies of aggressive use of new T2DM drugs instead of sulfonylureas and insulin are needed. Our statin results empirically validate two national guidelines for using statins in older patients with diabetes. However, 23% of study patients never took a statin, suggesting missed opportunities for prevention.
Delivering non-communicable disease interventions to women and children in conflict settings: a systematic review
Authors: Shah Shailja , Munyuzangabo Mariella , Gaffey Michelle F , Kamali Mahdis , Jain Reena P , Als Daina , Meteke Sarah , Radhakrishnan Amruta , Siddiqui Fahad J , Ataullahjan Anushka , Bhutta Zulfiqar A 
Published: April 2020

BackgroundNon-communicable diseases (NCDs) are the leading cause of death worldwide. In the context of conflict settings, population displacement, disrupted treatment, infrastructure damage and other factors impose serious NCD intervention delivery challenges, but relatively little attention has been paid to addressing these challenges. Here we synthesise the available indexed and grey literature reporting on the delivery of NCD interventions to conflict-affected women and children in low- and middle-income countries (LMICs).MethodsA systematic search in MEDLINE, Embase, CINAHL and PsycINFO databases for indexed articles published between 1 January 1990 and 31 March 2018 was conducted, and publications reporting on NCD intervention delivery to conflict-affected women or children in LMICs were included. A grey literature search of 10 major humanitarian organisation websites for publications dated between 1 January 2013 and 30 November 2018 was also conducted. We extracted and synthesised information on intervention delivery characteristics and delivery barriers and facilitators.ResultsOf 27 included publications, most reported on observational research studies, half reported on studies in the Middle East and North Africa region and 80% reported on interventions targeted to refugees. Screening and medication for cardiovascular disease and diabetes were the most commonly reported interventions, with most publications reporting facility-based delivery and very few reporting outreach or community approaches. Doctors were the most frequently reported delivery personnel. No publications reported on intervention coverage or on the effectiveness of interventions among women or children. Limited population access and logistical constraints were key delivery barriers reported, while innovative technology use, training of workforce and multidisciplinary care were reported to have facilitated NCD intervention delivery.ConclusionLarge and persistent gaps in information and evidence make it difficult to recommend effective strategies for improving the reach of quality NCD care among conflict-affected women and children. More rigorous research and reporting on effective strategies for delivering NCD care in conflict contexts is urgently needed.PROSPERO registration numberCRD42019125221
End-of-life communication in advanced cancer: international trends (2009–2014)
Authors: Verkissen Mariëtte N , Penders Yolanda W H , Onwuteaka-Philipsen Bregje D , Moreels Sarah , Donker Gé A , Vega Alonso Tomás , Van den Block Lieve , Deliens Luc 
Published: April 2020

ObjectiveTo examine trends in end-of-life communication with people with cancer in general practice.MethodsMortality follow-back survey among general practitioners (GPs) in representative epidemiological surveillance networks in Belgium (BE), the Netherlands (NL) and Spain (ES) in 2009–2010 (ES: 2010–2011) and 2013–2014. Using a standardised form, GPs registered all deceased adult patients in their practice and reported for five end-of-life care topics whether they had been discussed with the patient. Non-sudden cancer deaths were included (n=2306; BE: 1233; NL: 729; ES: 344).ResultsA statistically significant increase was found between 2009/2010 and 2014 in the prevalence of communication about diagnosis (from 84% to 94%) and options for end-of-life care (from 73% to 90%) in BE, and in GPs’ awareness of patients’ preferences for medical treatment and a proxy decision-maker in BE (from 41% and 20% up to 53% and 28%) and the NL (from 62% and 32% up to 70% and 52%). Communication about options for end-of-life care and psychosocial problems decreased in the NL (from 88% and 91% down to 73%) and ES (from 76% and 77% down to 26% and 39%).ConclusionConsiderable change in GP–patient communication seems possible in a relatively short time span, but communication cannot be assumed to increase over time. Increasing specialisation of care and task differentiation may lead to new roles in communication for healthcare providers in primary and secondary care. Improved information sharing between GPs and other healthcare providers may be necessary to ensure that patients have the chance to discuss important end-of-life topics.
Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction
Authors: Son Mi Kyoung , Park Jin Joo , Lim Nam-Kyoo , Kim Won-Ho , Choi Dong-Ju 
Published: April 2020

ObjectiveTo determine the prognostic value of atrial fibrillation (AF) in patients with heart failure (HF) and preserved, mid-range or reduced ejection fraction (EF).MethodsPatients hospitalised for acute HF were enrolled in the Korean Acute Heart Failure registry, a prospective, observational, multicentre cohort study, between March 2011 and February 2014. HF types were defined as reduced EF (HFrEF, LVEF <40%), mid-range EF (HFmrEF, LVEF 40%–49%) or preserved EF (HFpEF, LVEF ≥50%).ResultsOf 5414 patients enrolled, HFrEF, HFmrEF and HFpEF were seen in 3182 (58.8%), 875 (16.2%) and 1357 (25.1%) patients, respectively. The prevalence of AF significantly increased with increasing EF (HFrEF 28.9%, HFmrEF 39.8%, HFpEF 45.2%; p for trend <0.001). During follow-up (median, 4.03 years; IQR, 1.39–5.58 years), 2806 (51.8%) patients died. The adjusted HR of AF for all-cause death was 1.06 (0.93–1.21) in the HFrEF, 1.10 (0.87–1.39) in the HFmrEF and 1.22 (1.02–1.46) in the HFpEF groups. The HR for the composite of all-cause death or readmission was 0.97 (0.87–1.07), 1.14 (0.93–1.38) and 1.03 (0.88–1.19) in the HFrEF, HFmrEF and HFpEF groups, respectively, and the HR for stroke was 1.53 (1.03–2.29), 1.04 (0.57–1.91) and 1.90 (1.13–3.20), respectively. Similar results were observed after propensity score matching analysis.ConclusionsAF was more common with increasing EF. AF was seen to be associated with increased mortality only in patients with HFpEF and was associated with an increased risk of stroke in patients with HFrEF or HFpEF.Trial registration numberNCT01389843
Effect of meteorological factors and air pollutants on out-of-hospital cardiac arrests: a time series analysis
Authors: Kim Jin-Ho , Hong Jinwook , Jung Jaehun , Im Jeong-Soo 
Published: April 2020

ObjectivesWe aimed to investigate the effects of meteorological factors and air pollutants on out-of-hospital cardiac arrest (OHCA) according to seasonal variations because the roles of these factors remain controversial to date.MethodsA total of 38 928 OHCAs of cardiac origin that occurred within eight metropolitan areas between 2012 and 2016 were identified from the Korean nationwide emergency medical service database. A time series multilevel approach based on Poisson analysis following a Granger causality test was used to analyse the influence of air pollution and 13 meteorological variables on OHCA occurrence.ResultsParticulate matter (PM) ≤2.5 µm (PM2.5), average temperature, daily temperature range and humidity were significantly associated with a higher daily OHCA risk (PM2.5: 1.59%; 95% CI: 1.51% to 1.66% per 10µg/m3, average temperature 0.73%, 95% CI: 0.63% to 0.84% per 1°C, daily temperature range: 1.05%, 95% CI: 0.63% to 1.48% per 1°C, humidity −0.48, 95% CI: −0.40 to −0.56 per 1%) on lag day 1. In terms of the impact of these four risk factors in different seasons, average temperature and daily temperature range were highly associated with OHCA in the summer and winter, respectively. However, only PM2.5elevation (to varying extents) was an independent and consistent OHCA risk factor irrespective of the season.ConclusionsPM2.5, average temperature, daily temperature range and humidity were independently associated with OHCA occurrence in a season-dependent manner. Importantly, PM2.5was the only independent risk factor for OHCA occurrence irrespective of seasonal changes.
Ethics of resuscitation for extremely premature infants: a systematic review of argument-based literature
Authors: Cavolo Alice , Dierckx de Casterlé Bernadette , Naulaers Gunnar , Gastmans Chris 
Published: April 2020

ObjectiveTo present (1) the ethical concepts related to the debate on resuscitation of extremely premature infants (EPIs) as they are described in the ethical literature; and (2) the ethical arguments based on these concepts.DesignWe conducted a systematic review of the ethical literature. We selected articles based on the following predefined inclusion/exclusion criteria: (1) English language articles (2) presenting fully elaborated ethical arguments (3) on resuscitation (4) of EPIs, that is, infants born before 28 weeks of gestation.AnalysisAfter repeated reading of articles, we developed individual summaries, conceptual schemes and an overall conceptual scheme. Ethical arguments and concepts were identified and analysed.ResultsForty articles were included out of 4709 screened. Personhood, best interest, autonomy and justice were concepts grounding the various arguments. Regarding these concepts, included authors agreed that the best interest principle should guide resuscitation decisions, whereas justice seemed the least important concept. The arguments addressed two questions: Should we resuscitate EPIs? Who should decide? Included authors agreed that not all EPIs should be resuscitated but disagreed on what criteria should ground this decision. Overall, included authors agreed that both parents and physicians should contribute to the decision.ConclusionsThe included publications suggest that while the best interest is the main concept guiding resuscitation decisions, justice is the least important. The included authors also agree that both parents and physicians should be actively involved in resuscitation decisions for EPIs. However, our results suggest that parents’ decision should be over-ridden when in contrast with the EPI’s best interest.
Effective interactions in Ricci-Based Gravity below the non-metricity scale
Authors: Delhom Adrià , Miralles Victor , Peñuelas Ana 
Published: April 2020

AbstractWe show how minimally-coupled matter fields of arbitrary spin, when coupled to Ricci-based gravity theories, develop non-trivial effective interactions that can be treated perturbatively only below a characteristic high-energy scale $$\Lambda _{Q}$$ΛQ. We then use this interactions to set bounds on the high-energy scale $$\Lambda _{Q}$$ΛQ that controls departures of Ricci-Based Gravity theories from General Relativity. Particularly, for Eddington-inspired Born-Infeld gravity we obtain the strong bound $$ |\kappa |<10^{-26} \text {m}^5 \text {kg}^{-1}\text {s}^{-2} $$|κ|<10-26m5kg-1s-2.
Loss of a Negative Feedback Loop between IRF8 and AR Promotes Prostate Cancer Growth and Enzalutamide Resistance
Authors: Wu Hongxi , You Linjun , Li Yan , Zhao Zhili , Shi Guangjiang , Chen Zhen , Wang Zhuo , Li Xianjing , Du Shijia , Ye Wanli , Gao Xiaofang , Duan Jingjing , Cheng Yan , Tao Weiyan , Bian Jinsong , Zhou Jin-Rong , Zhu Qingyi , Yang Yong 
Published: April 2020

Abstract

In incurable castration-resistant prostate cancer (CRPC), resistance to the novel androgen receptor (AR) antagonist enzalutamide is driven mainly by AR overexpression. Here we report that the expression of interferon regulatory factor 8 (IRF8) is increased in primary prostate cancer but decreased in CRPC compared with normal prostate tissue. Decreased expression of IRF8 positively associated with CRPC progression and enzalutamide resistance. IRF8 interacted with AR and promoted its degradation via activation of the ubiquitin/proteasome systems. Epigenetic knockdown of IRF8 promoted AR-mediated prostate cancer progression and enzalutamide resistance in vitro and in vivo. Furthermore, IFNα increased expression of IRF8 and improved the efficacy of enzalutamide in CRPC by targeting the IRF8–AR axis. We also provide preliminary evidence for the efficacy of IFNα with hormonotherapy in a clinical study. Collectively, this study identifies IRF8 both as a tumor suppressor in prostate cancer pathogenesis and a potential alternative therapeutic option to overcome enzalutamide resistance.

Significance:
These findings identify IRF8-mediated AR degradation as a mechanism of resistance to AR-targeted therapy, highlighting the therapeutic potential of IFNα in targeting IRF8–AR axis in CRPC.
Theranostic Targeting of CUB Domain Containing Protein 1 (CDCP1) in Pancreatic Cancer
Authors: Moroz Anna , Wang Yung-Hua , Sharib Jeremy M. , Wei Junnian , Zhao Ning , Huang Yangjie , Chen Zhuo , Martinko Alexander J. , Zhuo Jie , Lim Shion A. , Zhang Lydia H. , Seo Youngho , Carlin Sean , Leung Kevin K. , Collisson Eric A. , Kirkwood Kimberly S. , Wells James A. , Evans Michael J. 
Published: April 2020

Abstract

Purpose:
The recent emergence of radioligand therapies for cancer treatment has increased enthusiasm for developing new theranostic strategies coupling both imaging and cytotoxicity in the same entity. In this study, we evaluated whether CUB domain containing protein 1 (CDCP1), a single-pass transmembrane protein highly overexpressed in diverse human cancers, might be a target for cancer theranostics.

Experimental Design:
The ectodomain of CDCP1 was targeted using radiolabeled forms of 4A06, a potent and specific recombinant human antibody that we developed. Imaging and antitumor assessment studies were performed in animal models of pancreatic cancer, including two patient-derived xenograft models we developed for this study. For antitumor assessment studies, the endpoints were death due to tumor volume &gt;3,000 mm3 or ≥20% loss in body weight. Specific tracer binding or antitumor effects were assessed with an unpaired, two-tailed Student t test and survival advantages were assessed with a log rank (Mantel–Cox) test. Differences at the 95% confidence level were interpreted to be significant.

Results:
89Zr-4A06 detected a broad dynamic range of full length or cleaved CDCP1 expression on seven human pancreatic cancer tumors (n = 4/tumor). Treating mice with single or fractionated doses of 177Lu-4A06 significantly reduced pancreatic cancer tumor volume compared with mice receiving vehicle or unlabeled 4A06 (n = 8; P &lt; 0.01). A single dose of 225Ac-4A06 also inhibited tumor growth, although the effect was less profound compared with 177Lu-4A06 (n = 8; P &lt; 0.01). A significant survival advantage was imparted by 225Ac-4A06 (HR = 2.56; P &lt; 0.05).

Conclusions:
These data establish that CDCP1 can be exploited for theranostics, a finding with widespread implications given its breadth of overexpression in cancer.
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer
Authors: Parker Seth J. , Amendola Caroline R. , Hollinshead Kate E.R. , Yu Qijia , Yamamoto Keisuke , Encarnación-Rosado Joel , Rose Rebecca E. , LaRue Madeleine M. , Sohn Albert S.W. , Biancur Doug E. , Paulo Joao A. , Gygi Steven P. , Jones Drew R. , Wang Huamin , Philips Mark R. , Bar-Sagi Dafna , Mancias Joseph D. , Kimmelman Alec C. 
Published: April 2020

Abstract

Pancreatic ductal adenocarcinoma (PDAC) evolves a complex microenvironment comprised of multiple cell types, including pancreatic stellate cells (PSC). Previous studies have demonstrated that stromal supply of alanine, lipids, and nucleotides supports the metabolism, growth, and therapeutic resistance of PDAC. Here we demonstrate that alanine cross-talk between PSCs and PDAC is orchestrated by the utilization of specific transporters. PSCs utilize SLC1A4 and other transporters to rapidly exchange and maintain environmental alanine concentrations. Moreover, PDAC cells upregulate SLC38A2 to supply their increased alanine demand. Cells lacking SLC38A2 fail to concentrate intracellular alanine and undergo a profound metabolic crisis resulting in markedly impaired tumor growth. Our results demonstrate that stromal–cancer metabolic niches can form through differential transporter expression, creating unique therapeutic opportunities to target metabolic demands of cancer.

Significance:
This work identifies critical neutral amino acid transporters involved in channeling alanine between pancreatic stellate and PDAC cells. Targeting PDAC-specific alanine uptake results in a metabolic crisis impairing metabolism, proliferation, and tumor growth. PDAC cells specifically activate and require SLC38A2 to fuel their alanine demands that may be exploited therapeutically.
This article is highlighted in the In This Issue feature, p. 890
Coronavirus Disease 2019 in a Hemodialysis Patient
Authors: Yuan Hai , Guo E. , Gao Zhao , Hu Fengqi , Lu Li 
Published: April 2020

There has been a global outbreak of the coronavirus disease 2019 (COVID-19) since December 2019. Here, we describe the case of a 49-year-old male undergoing maintenance hemodialysis (HD) who got infected with COVID-19 and our experience in performing HD for him. The patient’s symptoms and lung imaging changes were atypical. However, his lymphocyte range decreased upon admission and the polymerase chain reaction of the pharyngeal swab for the ­COVID-19 nucleic acid was positive. The patient developed respiratory failure and required mechanical ventilation 8 days after admission. In the end, he died from multiple organ dysfunction syndrome. The difficulties in diagnosis, infection control, and treatment of COVID-19 in maintenance HD patients are discussed in this report.
Marcelo Neves. Constituição e direito na modernidade periférica: uma abordagem teórica e uma interpretação do caso brasileiro
Authors: Carvalho Alexandre Douglas Zaidan de 
Published: April 2020

Resenha do livro de Marcelo Neves. Constituição e direito na modernidade periférica: uma abordagem teórica e uma interpretação do caso brasileiro, São Paulo, Martins Fontes, 2018.
El movimiento obrero organizado ante la ofensiva de la oligarquía financiera
Authors: Carrera Nicolás Iñigo , Fernandez Fabián , Cotarelo María Celia 
Published: April 2020

En diciembre de 2015 retornó al gobierno la fuerza social acaudillada por la oligarquía financiera dando continuidad al período contrarrevolucionario iniciado a mediados de la década de 1970 que acompaña el desarrollo del capitalismo predominantemente en profundidad y genera una creciente masa de población sobrante para las necesidades del capital. Ese retorno, en un momento descendente de la lucha de la clase obrera, fue posible por la fractura del movimiento sindical y de la alianza social popular. Los resultados de la política económica del nuevo gobierno fueron una fuerte caída de la actividad productiva, aumento de la desocupación, fuerte inflación con deterioro del salario real e importante crecimiento de la pobreza. Pronto comenzaron las protestas, tanto de la capa más acomodada de la clase obrera como de la más pobre, que en general, y a diferencia de las décadas anteriores, no sólo se movilizaron conjuntamente sino establecieron relaciones orgánicas, a pesar de las numerosas fracciones político-sindicales en que estaban divididas. La resistencia se manifestó en seis huelgas generales y numerosas protestas callejeras entre las que se destaca la de diciembre de 2017, que desbordó el sistema institucional. Las demandas sindicales planteadas apuntaron a reivindicaciones económicas inmediatas (paritarias libres, contra despidos) y contra la política económica del gobierno en general, especialmente contra la implementación de las reformas laboral, jubilatoria y tributaria y el acuerdo con el FMI.