bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of armed conflict on cardiovascular disease risk: a systematic review
Authors: Jawad Mohammed , Vamos Eszter P , Najim Muhammad , Roberts Bayard , Millett Christopher 
Published: May 2019

ObjectivesProlonged armed conflict may constrain efforts to address non-communicable disease in some settings. We assessed the impact of armed conflict on cardiovascular disease (CVD) risk among civilians in low/middle-income countries (LMICs).MethodsIn February 2019, we performed a systematic review searching Medline, Embase, PsychINFO, Global Health and Web of Science without language or date restrictions. We included adult, civilian populations in LMICs. Outcomes included CVDs and diabetes, and eight clinical and behavioural factors (blood pressure, blood glucose, lipids, tobacco, alcohol, body mass index, nutrition, physical activity). We systematically reanalysed data from original papers and presented them descriptively.ResultsSixty-five studies analysed 23 conflicts, and 66% were of low quality. We found some evidence that armed conflict is associated with an increased coronary heart disease, cerebrovascular and endocrine diseases, in addition to increased blood pressure, lipids, alcohol and tobacco use. These associations were more consistent for mortality from chronic ischaemic heart disease or unspecified heart disease, systolic blood pressure and tobacco use. Associations between armed conflict and other outcomes showed no change, or had mixed or uncertain evidence. We found no clear patterning by conflict type, length of follow-up and study quality, nor strong evidence for publication bias.ConclusionsArmed conflict may exacerbate CVDs and their risk factors, but the current literature is somewhat inconsistent. Postconflict reconstruction efforts should deliver low-resource preventative interventions through primary care to prevent excess CVD-related morbidity and mortality.PROSPERO registration numberCRD42017065722
Diagnosis of acute myocardial infarction in the presence of left bundle branch block
Authors: Nestelberger Thomas , Cullen Louise , Lindahl Bertil , Reichlin Tobias , Greenslade Jaimi H , Giannitsis Evangelos , Christ Michael , Morawiec Beata , Miro Oscar , Martín-Sánchez Francisco Javier , Wussler Desiree Nadine , Koechlin Luca , Twerenbold Raphael , Parsonage William , Boeddinghaus Jasper , Rubini Gimenez Maria , Puelacher Christian , Wildi Karin , Buerge Tobias , Badertscher Patrick , DuFaydeLavallaz Jeanne , Strebel Ivo , Croton Lukas , Bendig Garnet , Osswald Stefan , Pickering John William , Than Martin , Mueller Christian 
Published: May 2019

ObjectivePatients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician.MethodsWe prospectively evaluated the incidence of AMI and diagnostic performance of specific ECG and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. The final diagnosis of AMI was centrally adjudicated by two independent cardiologists according to the universal definition of myocardial infarction.ResultsAmong 8830 patients, LBBB was present in 247 (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1%–12%) but high specificity (95%–100%) for AMI. The diagnostic accuracy as quantified by the receiver operating characteristics (ROC) curve of hs-cTnT and hs-cTnI concentrations at presentation (area under the ROC curve (AUC) 0.91, 95% CI 0.85 to 0.96 and AUC 0.89, 95% CI 0.83 to 0.95), as well as that of their 0/1-hour and 0/2-hour changes, was very high. A diagnostic algorithm combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1 hour or 2 hours derived in cohort 1 (45 of 45(100%) patients with AMI correctly identified) showed high efficacy and accuracy when externally validated in cohorts 2 and 3 (28 of 29 patients, 97%).ConclusionMost patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with hs-cTnT/I testing at 0/1 hour or 0/2 hours allows early and accurate diagnosis of AMI in LBBB.Trial registration numberAPACE:NCT00470587; ADAPT: ACTRN12611001069943; TRAPID-AMI: RD001107;Results.
From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials
Authors: Hovland-Tånneryd Ann , Melin Michael , Hägglund Ewa , Hagerman Inger , Persson Hans E 
Published: May 2019

ObjectivesA home-based tool for heart failure (HF) patients, was evaluated in a specialist setting as a randomised controlled trial (RCT) and also in a validation cohort in a primary care setting in a clinical controlled trial (CCT). The tool provides education, symptom monitoring and titration of diuretics. The aim of this study was thus to extend validity of the previous RCT findings in order to describe applicability of the tool in clinical practice.MethodsData from both trials were analysed separately, as well as a pooled data set (n=172). Data were analysed with respect to HF related in-hospital days, self-care behaviour and system adherence, during a 6-month intervention. The analysis of in-hospital days for the pooled data was adjusted for baseline differences between the two study cohorts, relating to disease state.ResultsIn the RCT (n=72) the intervention group (IG) consisted of 32 patients and the control group (CG) of 40 patients. The risk ratio (RR) for in-hospital days was RR: 0.72, 95% CI 0.61 to 0.84, p<0.05 in favour of the IG. In the CCT (n=100) both the IG and the CG consisted of 50 patients and the IG had fewer in-hospitals days, comparable to the RCT findings with RR: 0.67; 95% CI 0.45 to 0.99; p<0.05. For the pooled data set made up of 172 patients, the groups were well balanced but with a higher prevalence of hypertension in the CG. The RR relating to in-hospital days for the pooled data set was 0.71; 95% CI 0.61 to 0.82; p<0.05 in favour of the IG. There was a statistically significant improvement in self-care by 27% and the median system adherence was 94%.ConclusionsThese analyses suggest that the evaluated tool might reduce HF related in-hospital days in the general HF population, which adds to the external validity of previous findings.Clinical Trial RegistrationNCT03655496.
Evaluation of the performances of ‘typical’ imaging abnormalities of axial spondyloarthritis: results of the cross-sectional ILOS-DESIR study
Authors: Molto Anna , Gossec Laure , Lefèvre-Colau Marie-Martine , Foltz Violaine , Beaufort Romain , Laredo Jean-Denis , Richette Pascal , Dieude Philippe , Goupille Philippe , Feydy Antoine , Dougados Maxime 
Published: May 2019

ObjectiveTo evaluate the prevalence and performance as axial Spondyloarthritis (axSpA) diagnostic feature of radiographic and MRI lesions ‘typical’ of axSpA of the sacroiliac joint (SIJ) and spine in a mechanical chronic back pain (CBP) population and in an axSpA cohort.MethodsCross-sectional multicentre study. Patients: (1) recent onset axSpA (DESIR cohort) and (2) mechanical non-axSpA CBP matched for age and gender (ILOS study). Imaging: radiographs and MR scans were performed identically in both groups. All images were centrally read, blinded for diagnosis and for other imaging findings in the same patient. Statistical analysis: prevalence of lesions ‘typical of axSpA’ were compared in both groups. Sensitivity, specificity and positive likelihood ratios (LR+) of each lesion (and combination of lesions) were calculated.ResultsA total of 98 patients with CBP were included, and compared with 100 patients with recent onset axSpA. SIJ lesions were consistently more frequent in the axSpA group (35.0% vs 11.8% p<0.001, 35.0% vs 8.4% p<0.001% and 32.0% vs 10.0%. p<0.001 for modified New York criteria, MRI sacroiliitis and ≥3 erosions of the SIJ on MRI, respectively), and performed well (LR+ for ≥3 erosions 3.0 (95% CI 1.6 to 5.8)). Spine lesions were comparable across groups: radiographic lesions were rare, while all MRI lesions were frequent.ConclusionOur study confirms that ‘typical’ lesions can also be observed in patients with non-axSpA CBP but that SIJ lesions by all modalities remain the most valuable for diagnosis, including structural lesions of the SIJ. This suggests the potential interest of adding MRI SIJ structural lesions in the definition of MRI abnormalities for axSpA classification.
Immediate effects of a novel walking assist device with auxiliary illuminator on patients after acute strokes
Authors: Huang Wan-Yun , Tuan Sheng-Hui , Li Min-Hui , Liu Xin-Yu , Hsu Pei-Te 
Published: May 2019

Background: Many patients after acute stage of stroke are present with abnormal gait pattern due to weakness or hypertonicity of the affected limbs. Facilitation of normal gait is a primary goal of rehabilitation on these patients. Objective: We aimed to investigate whether walking assist device with auxiliary illuminator (quad-cane with laser) providing visual feedback during ambulation could improve parameters of gait cycle immediately among patients with subacute and chronic stroke. Methods: This was a cross-sectional study and 30 participants (male 23, female 7, group 1) with mean age [Formula: see text] years were recruited. Among them, 22 used ankle-foot orthosis [(AFO), group 2] and 8 did not use AFO (group 3) at usual walking. All the participants walked along a strait corridor with even surface for 20[Formula: see text]m without and with using a quad-cane with laser, respectively. A gait analyzer (Reha-Watch1 system) was used to measure the changes of the parameters of gait cycle, including stride length, cadence, gait speed, stance phase, swing phase, duration of single support and double support, the angle between toes and the ground at the time of toe-off (the toe-off angle) and the angle between calcaneus and the ground at the time of heel-strike (the heel-strike angle), before and with the use of a quad-cane with laser. Results: The increase in the heel-strike angle reached a significant difference in groups 1 2, and 3 ([Formula: see text], and [Formula: see text], respectively). However, the stride length, the gait speed, the cadence, percentage of the stance phase, swing phase, single-support phase, and double-support phase in a gait cycle, and the toe-off angle showed no significant change with the use of quad-cane with laser. Conclusion: Patients after acute stroke had an immediate and significant increase in the heel-stroke angle by using a quad-cane with laser during ambulation, which might help the patients to reduce knee hyperextension moment and lessen the pressure of heel at loading phase.
Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes
Authors: Ganesan Murali , Krutik Vjaceslav M. , Makarov Edward , Mathews Saumi , Kharbanda Kusum K. , Poluektova Larisa Y. , Casey Carol A , Osna Natalia A. 
Published: May 2019

Hepatitis B virus (HBV) infection and alcoholism are major public health problems worldwide, contributing to the development of end-stage liver disease. Alcohol intake affects HBV infection pathogenesis and treatment outcomes. HBV-specific cytotoxic T lymphocytes (CTLs) play an important role in HBV clearance. Many previous studies have focused on alcohol-induced impairments of the immune response. However, it is not clear whether alcohol alters the presentation of HBV peptide-major histocompatibility complex (MHC) class I complexes on infected hepatocytes resulting in escape of its recognition by CTLs. Hence, the focus of this study was to investigate the mechanisms by which ethanol metabolism affects the presentation of CTL epitope on HBV-infected hepatocytes. As demonstrated here, although continuous cell exposure to acetaldehyde-generating system (AGS) increased HBV load in HepG2.2.15 cells, it decreased the expression of HBV core peptide 18–27-human leukocyte antigen-A2complex (CTL epitope) on the cell surface. Moreover, we observed AGS-induced suppression of chymotrypsin- and trypsin-like proteasome activities necessary for peptide processing by proteasome as well as a decline in IFNγ-stimulated immunoproteasome (IPR) function and expression of PA28 activator and immunoproteasome subunits LMP7 and LMP2. Furthermore, IFNγ-induced activation of peptide-loading complex (PLC) components, such as transporter associated with antigen processing (TAP1) and tapasin, were suppressed by AGS. The attenuation of IPR and PLC activation was attributed to AGS-triggered impairment of IFNγ signaling in HepG2.2.15 cells. Collectively, all these downstream events reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, which may suppress CTL activation and the recognition of CTL epitopes on HBV-expressing hepatocytes by immune cells, thereby leading to persistence of liver inflammation.NEW & NOTEWORTHY Our study shows that in HBV-expressing HepG2.2.15 cells, acetaldehyde alters HBV peptide processing by suppressing chymotrypsin- and trypsin-like proteasome activities and decreases IFNγ-stimulated immunoproteasome function and expression of PA28 activator and immunoproteasome subunits. It also suppresses IFNγ-induced activation of peptide-loading complex (PLC) components due to impairment of IFNγ signaling via the JAK-STAT1 pathway. These acetaldehyde-induced dysfunctions reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, thereby leading to persistence of HBV infection.
A critical time window for recovery extends beyond one-year post-stroke
Authors: Ballester Belén Rubio , Maier Martina , Duff Armin , Cameirão Mónica , Bermúdez Sergi , Duarte Esther , Cuxart Ampar , Rodríguez Susana , San Segundo Mozo Rosa María , Verschure Paul F. M. J. 
Published: May 2019

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patient’s chronicity remain unclear. The field has widely accepted the notion of a proportional recovery rule with a “critical window for recovery” within the first 3–6 mo poststroke. This hypothesis justifies the general cessation of physical therapy at chronic stages. However, the limits of this critical window have, so far, been poorly defined. In this analysis, we address this question, and we further explore the temporal structure of motor recovery using individual patient data from a homogeneous sample of 219 individuals with mild to moderate upper-limb hemiparesis. We observed that improvement in body function and structure was possible even at late chronic stages. A bootstrapping analysis revealed a gradient of enhanced sensitivity to treatment that extended beyond 12 mo poststroke. Clinical guidelines for rehabilitation should be revised in the context of this temporal structure. NEW & NOTEWORTHY Previous studies in humans suggest that there is a 3- to 6-mo “critical window” of heightened neuroplasticity poststroke. We analyze the temporal structure of recovery in patients with hemiparesis and uncover a precise gradient of enhanced sensitivity to treatment that expands far beyond the limits of the so-called critical window. These findings highlight the need for providing therapy to patients at the chronic and late chronic stages.
IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion
Authors: Conlon Kevin C. , Potter E. Lake , Pittaluga Stefania , Lee Chyi-Chia Richard , Miljkovic Milos D. , Fleisher Thomas A. , Dubois Sigrid , Bryant Bonita R. , Petrus Michael , Perera Liyanage P. , Hsu Jennifer , Figg William D. , Peer Cody J. , Shih Joanna H. , Yovandich Jason L. , Creekmore Stephen P. , Roederer Mario , Waldmann Thomas A. 
Published: May 2019

Abstract

Purpose:
The first-in-human clinical trial with human bolus intravenous infusion IL15 (rhIL15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and clinical activity of rhIL15 administered as a 10-day continuous intravenous infusion (CIV) to patients with cancers in a phase I trial.

Patients and Methods:
Patients received treatment for 10 days with CIV rhIL15 in doses of 0.125, 0.25, 0.5, 1, 2, or 4 μg/kg/day. Correlative laboratory tests included IL15 pharmacokinetic (PK) analyses, and assessment of changes in lymphocyte subset numbers.

Results:
Twenty-seven patients were treated with rhIL15; 2 μg/kg/day was identified as the MTD. There were eight serious adverse events including two bleeding events, papilledema, uveitis, pneumonitis, duodenal erosions, and two deaths (one due to likely drug-related gastrointestinal ischemia). Evidence of antitumor effects was observed in several patients, but stable disease was the best response noted. Patients in the 2 μg/kg/day group had a 5.8-fold increase in number of circulating CD8+ T cells, 38-fold increase in total NK cells, and 358-fold increase in CD56bright NK cells. Serum IL15 concentrations were markedly lower during the last 3 days of infusion.

Conclusions:
This phase I trial identified the MTD for CIV rhIL15 and defined a treatment regimen that produced significant expansions of CD8+ T and NK effector cells in circulation and tumor deposits. This regimen has identified several biological features, including dramatic increases in numbers of NK cells, supporting trials of IL15 with anticancer mAbs to increase antibody-dependent cell-mediated cytotoxicity and anticancer efficacy.
Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer
Authors: Magbanua Mark Jesus M. , Yau Christina , Wolf Denise M. , Lee Jin Sun , Chattopadhyay Aheli , Scott Janet H. , Bowlby-Yoder Erin , Hwang E. Shelley , Alvarado Michael , Ewing Cheryl A. , Delson Amy L. , van't Veer Laura J. , Esserman Laura , Park John W. 
Published: May 2019

Abstract

Purpose:
We examined the prognostic impact of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) detected at the time of surgery in 742 untreated patients with early breast cancer.

Experimental Design:
DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) assay. CTCs in blood were enumerated either by IE/FC or CellSearch. Median follow-up was 7.1 years for distant recurrence-free survival (DRFS) and 9.1 years for breast cancer–specific survival (BCSS) and overall survival (OS). Cox regressions were used to estimate hazard ratios for DRFS, BCSS, and OS in all patients, as well as in hormone receptor–positive (HR-positive, 87%) and HR-negative (13%) subsets.

Results:
In multivariate models, CTC positivity by IE/FC was significantly associated with reduced BCSS in both all (n = 288; P = 0.0138) and HR-positive patients (n = 249; P = 0.0454). CTC positivity by CellSearch was significantly associated with reduced DRFS in both all (n = 380; P = 0.0067) and HR-positive patients (n = 328; P = 0.0002). DTC status, by itself, was not prognostic; however, when combined with CTC status by IE/FC (n = 273), double positivity (CTC+/DTC+, 8%) was significantly associated with reduced DRFS (P = 0.0270), BCSS (P = 0.0205), and OS (P = 0.0168). In HR-positive patients, double positivity (9% of 235) was significantly associated with reduced DRFS (P = 0.0285), BCSS (P = 0.0357), and OS (P = 0.0092).

Conclusions:
Detection of CTCs in patients with HR-positive early breast cancer was an independent prognostic factor for DRFS (using CellSearch) and BCSS (using IE/FC). Simultaneous detection of DTCs provided additional prognostic power for outcome, including OS.
EC359: A First-in-Class Small-Molecule Inhibitor for Targeting Oncogenic LIFR Signaling in Triple-Negative Breast Cancer
Authors: Viswanadhapalli Suryavathi , Luo Yiliao , Sareddy Gangadhara R. , Santhamma Bindu , Zhou Mei , Li Mengxing , Ma Shihong , Sonavane Rajni , Pratap Uday P. , Altwegg Kristin A. , Li Xiaonan , Chang Annabel , Chávez-Riveros Alejandra , Dileep Kalarickal V. , Zhang Kam Y.J. , Pan Xinlei , Murali Ramachandran , Bajda Marek , Raj Ganesh V. , Brenner Andrew J. , Manthati Vijaya , Rao Manjeet K. , Tekmal Rajeshwar R. , Nair Hareesh B. , Nickisch Klaus J. , Vadlamudi Ratna K. 
Published: May 2019

Abstract
Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a critical role in cancer progression, metastasis, stem cell maintenance, and therapy resistance. Here, we describe a rationally designed first-in-class inhibitor of LIFR, EC359, which directly interacts with LIFR to effectively block LIF/LIFR interactions. EC359 treatment exhibits antiproliferative effects, reduces invasiveness and stemness, and promotes apoptosis in triple-negative breast cancer (TNBC) cell lines. The activity of EC359 is dependent on LIF and LIFR expression, and treatment with EC359 attenuated the activation of LIF/LIFR-driven pathways, including STAT3, mTOR, and AKT. Concomitantly, EC359 was also effective in blocking signaling by other LIFR ligands (CTF1, CNTF, and OSM) that interact at LIF/LIFR interface. EC359 significantly reduced tumor progression in TNBC xenografts and patient-derived xenografts (PDX), and reduced proliferation in patient-derived primary TNBC explants. EC359 exhibits distinct pharmacologic advantages, including oral bioavailability, and in vivo stability. Collectively, these data support EC359 as a novel targeted therapeutic that inhibits LIFR oncogenic signaling.
See related commentary by Shi et al., p. 1337
a. d. viiii Kalendas Octobres, dies natalis Augusti. Some Considerations on the Astronomical Orientation of Roman Cologne and the Imperial Cult
Authors: Espinosa-Espinosa David , González-García A. César 
Published: May 2019

Abstract
A key factor in planning and orienting towns in the Roman world, and in particular in Augustan towns, was cosmology. The application of cosmological criteria in these towns, associated with specific political and religious principles of the principate of Augustus, has been already identified in Italia, Gallia, and Hispania. In this article we examine the orientation of the Roman town of Ara Ubiorum (present day Cologne) that could be related with the dies natalis Augusti. Based on these results, such a relation could have been deliberately sought by Roman and Ubian authorities to connect the newly founded town, where there was an ara of the Imperial cult probably consecrated to Rome and Augustus, with Augustus, who was identified with Apollo-Sol.
Occultist Identity Formations Between Theosophy and Socialism in fin-de-siècle France
Authors: Strube Julian 
Published: May 2019

Abstract
Fin-de-siècle occultism is usually regarded within the context of an “occult revival” that implies the modernization of an older esoteric tradition. However, this notion is rooted in esoteric identificatory discourses at the end of the nineteenth century. This article will discuss two major aspects of these discourses. First, French esotericists polemically distanced themselves from the “Eastern” esotericism of the Theosophical Society by constructing an ésotérisme occidental. It will be shown that this separation of “East” and “West” occurred as a reaction to the T.S., and should thus be seen as a “nationalist” response to a global phenomenon. Second, another major aspect of occultist identity formations will be highlighted: socialism. It will be shown that fin-de-siècle occultists were deeply involved with socialist theories in the July Monarchy vein but ambiguously distanced themselves from contemporary “materialist” socialisms. An analysis of this context will further help to understand the construction of an esoteric tradition.