bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia
Authors: Jabbour Elias , Short Nicholas J. , Ravandi Farhad , Huang Xuelin , Xiao Lianchun , Garcia‐Manero Guillermo , Plunkett William , Gandhi Varsha , Sasaki Koji , Pemmaraju Naveen , Daver Naval G. , Borthakur Gautam , Jain Nitin , Konopleva Marina , Estrov Zeev , Kadia Tapan M. , Wierda William G. , DiNardo Courtney D. , Brandt Mark , O'Brien Susan M. , Cortes Jorge E. , Kantarjian Hagop 
Published: July 2017

BACKGROUNDFludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML).METHODSHerein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine.RESULTSThe complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event‐free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60‐day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2‐year event‐free survival rate: 58% vs 30% [P = .05] and 2‐year overall survival rate: 72% vs 36% [P = .009]).CONCLUSIONSCIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430‐9. © 2017 American Cancer Society.
Prevalence, risk factors, and neurobehavioral comorbidities of epilepsy in Kenyan children
Authors: Kind Charles J. , Newton Charles R. J. C. , Kariuki Symon M. ,   the Neurodevelopment Disorders study group
Published: July 2017

SummaryObjectiveTo investigate the prevalence, risk factors, clinical features, and neurobehavioral comorbidities of epilepsy and acute symptomatic seizures in school‐aged children in Kilifi, Kenya.MethodsRandomly selected children (N = 11,223) were screened for epilepsy and other neurodevelopmental disorders. Those who screened positive were invited for further clinical, electroencephalographic (EEG), and neuropsychological evaluations. Prevalence was measured by dividing cases by screened population, providing Agresti–Coull confidence intervals (CIs). Prevalence ratios were computed using log binomial regression, and odds ratios (ORs) were computed using logistic regression; both were implemented with generalized linear models. Attention‐deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental impairments were assessed in cases and controls.ResultsPrevalence of lifetime epilepsy was 20.9 per 1,000 (95% CI = 18.4–23.7), and that of active epilepsy was 11.5 per 1,000 (95% CI = 9.7–13.6). Prevalence of acute symptomatic seizures was 68.8 per 1,000 (95% CI = 64.2–73.6). Acute symptomatic seizures preceded a diagnosis of epilepsy in 8% of children. Of 98 children diagnosed with epilepsy, focal seizures were seen in 79%, abnormal EEG was seen in 39%, and 83% were not receiving antiepileptic drugs. Childhood absence epilepsy and Lennox–Gastaut epilepsy were the most easily identifiable epilepsy syndromes. Perinatal complications, previous hospitalization, geophagia, and snoring were risk factors for epilepsy. Family history of seizures, abnormal pregnancy, previous hospitalization, and snoring were risk factors for acute symptomatic seizures. Neurobehavioral comorbidities were present in 54% of subjects with lifetime epilepsy and in 3% of controls, with associations for individual comorbidities being statistically significant: ADHD (OR = 14.55, 95% CI = 7.54–28.06), ASD (OR = 36.83, 95% CI = 7.97–170.14), and cognitive impairments (OR = 14.55, 95% CI = 3.52–60.14).SignificanceThe burden of seizure disorders in this area is higher than in locations in high‐income countries, and can be reduced by preventing risk factors. A comprehensive management plan for neurobehavioral comorbidities of epilepsy should be incorporated into standard epilepsy care.
The ecotoxicity of zinc and zinc-containing substances in soil with consideration of metal-moiety approaches and organometal complexes
Authors: Ritchie Ellyn , Boyd Patrick , Lawson-Halasz Annamaria , Hawari Jalal , Saucier Stacey , Scroggins Richard , Princz Juliska 
Published: July 2017

Abstract

Within Canada, screening-level assessments for chemical substances are required to determine whether the substances pose a risk to human health and/or the environment, and as appropriate, risk management strategies. In response to the volume of metal and metal-containing substances, process efficiencies were introduced using a metal-moiety approach, whereby substances that contain a common metal moiety are assessed simultaneously as a group, with the moiety of concern consisting of the metal ion. However, for certain subgroups, such as organometals or organic metal salts, the organic moiety or parent substance may be of concern, rather than simply the metal ion. To further investigate the need for such additional consideration, certain substances were evaluated: zinc (Zn)-containing inorganic (Zn chloride [ZnCl2] and Zn oxide) and organic (organometal: Zn diethyldithiocarbamate [Zn(DDC)2] and organic metal salts (Zn stearate [ZnSt] and 4-chloro-2-nitrobenzenediazonium tetrachlorozincate [BCNZ]). The toxicity of the substances were assessed using plant (Trifolium pratense and Elymus lanceolatus) and soil invertebrate (Folsomia candida and Eisenia andrei) tests in a sandy soil. Effect measures were determined based on total metal and total parent analyses (for organic substances). In general, the inorganic Zn substances were less toxic than the organometals and organic metal salts, with 50% effective concentrations ranging from 11 to &gt;5194 mg Zn kg−1 dry soil. The data demonstrate the necessity for alternate approaches in the assessment of organo–metal complexes, with the organic moieties or parent substances warranting consideration rather than the metal ion alone. In this instance, the organometals and organic metal salts were significantly more toxic than other test substances despite their low total Zn content. Environ Toxicol Chem 2017;36:3324–3332. © 2017 Crown in the Right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.
Role of C1q complement fixing antibody assay in therapeutic plasma exchange management of pediatric cardiac antibody mediated rejection
Authors: Onwuemene Oluwatoyosi A. , Heath Deneen M. , Hartman Carol , Wong Edward C.C. 
Published: July 2017

AbstractPediatric cardiac transplant patients with antibody‐mediated rejection (AMR) often undergo therapeutic plasma exchange (TPE) to remove pathologic donor specific antibodies (DSA). In cases where DSA persist, it is unclear how long TPE should be continued. We report a case of a 17‐year‐old cardiac transplant patient with AMR where use of a C1q complement fixing antibody assay helped guide TPE cessation. This report adds to the existing literature that highlights the potential clinical significance of C1q antibodies in AMR management.
Human biliverdin reductase regulates the molecular mechanism underlying cancer development
Authors: Zhang Min , Xin Wei , Yi Zhi , Li Yue , Liu Ying , Zhang Hongyue , Chen He , Chen Xinxin , Tan Shujie , Zhu Daling 
Published: July 2017

AbstractHuman biliverdin reductase (hBVR), is an enzyme, that converts biliverdin to bilirubin, and has been implicated in epithelial‐mesenchymal transition (EMT) in breast cancer. However, few studies have investigated the role of hBVR in cell apoptosis in other cancers. Therefore, the aim of this study was to investigate the effects of hBVR in several lines of cancer cells. The results of this study showed that hBVR expression was up‐regulated in breast, lung, and liver cancers, but not ovarian cancer. Moreover, hBVR inhibition by small interfering RNA (si‐hBVR) attenuated cell survival and increased caspase‐3 protein expression, which was mediated by the ERK1/2 signaling pathway in relative cancer cells. In addition, the mitochondrial membrane potential and mitochondrial membrane proteins Bcl‐2 and BAX were found to be necessary for activation of the mitochondria dependent apoptosis pathway. Collectively, these findings indicated, for the first time, that the anti‐apoptotic effect of hBVR in cancers which portend new strategies for developing novel biomarkers and effective treatment ways for cancer patients.
The mechanism of long non‐coding RNA MEG3 for hepatic ischemia‐reperfusion: Mediated by miR‐34a/Nrf2 signaling pathway
Authors: Huang Xinli , Gao Yun , Qin Jianjie , Lu Sen 
Published: July 2017

AbstractTo investigate the function of MEG3 in hepatic ischemia‐reperfusion (HIR) progress, involving its association with the level of miR‐34a during hypoxia‐induced hypoxia re‐oxygenation (H/R) in vitro. HIR mice model in vivo was established. MEG3, miR‐34a expression, along with Nrf2 mRNA and protein level were detected in tissues and cells. Serum biochemical parameters (ALT and AST) were assessed in vivo. A potential binding region between MEG3 and miR34a was confirmed by luciferase assays. Hepatic cells HL7702 were subjected to hypoxia treatment in vitro for functional studies, including TUNEL‐positive cells detection and ROS analysis. MEG3, Nrf2 expression was significantly down‐regulated in infarction lesion from HIR mice, as opposed to increased miR‐34a production, while similar results were also observed in H/R HL7702 cells, while the above effects were reversed by MEG3 over‐expression. By using bioinformatics study and RNA pull down combined with luciferase assays, we demonstrated that MEG3 functioned as a competing endogenous RNA (ceRNA) for miR‐34a, and there was reciprocal repression between MEG3 and miR‐34a in an Argonaute 2‐dependent manner. Functional studies demonstrated that MEG3 showed positive regulation on TUNEL‐positive cells and ROS level. Further in vivo study confirmed that MEG3 over‐expression could improve hepatic function of HIR mice, and markedly decreased the expression of serum ALT and AST. MEG3 protected hepatocytes from HIR injury through down‐regulating miR‐34a expression, which could add our understanding of the molecular mechanisms in HIR injury.
Evaluation of short‐term effectiveness of eight targeted agents combined with chemotherapy for treating esophageal‐gastric junction adenocarcinoma: A network meta‐analysis
Authors: He Yong‐Ming , Yu Chen , Li Wei‐Bing , Li Zhi‐Peng , Xu Nan 
Published: July 2017

AbstractThis study aimed to evaluate the short‐term effectiveness of eight targeted agents (ramucirumab, bevacizumab, rilotumumab, panitumumab, cetuximab, trebananib, trastuzumab, matuzumab) plus chemotherapy in esophageal‐gastric junction adenocarcinoma (EGJA) by a network meta‐analysis (NMA). PubMed, Embase, and Cochrane Library databases were systematically retrieved for randomized clinical trials (RCTs) concerning targeted agents plus chemotherapy in the treatment of EGJA. This NMA combined both direct and indirect evidence to evaluate odds ratio (OR) and to draw the surface under the cumulative ranking curve (SUCRA). In total 11 RCTs with 3649 EGJA patients (1907 patients treated with targeted agents plus chemotherapy were regarded as the case group, and 1742 patients with placebo plus chemotherapy were assigned into the control group) were enrolled in this study. Targeted agents in terms of stable disease (SD), partial response (PR), disease control rate (DCR), and overall response ratio (ORR) with the SUCRA values of 0.838, 0.807, 0.934, and 0.793, respectively. Cetuximab and trastuzumab, with the SUCRA values of 0.884 and 0.758, came on top as the best outcomes for treating EGJA in terms of progressive disease (PD) and complete response (CR). Cluster analysis results indicated that ramucirumab plus chemotherapy might be the optimal treatment for EGJA. Our findings indicated that ramucirumab plus chemotherapy might be the optimal treatment for EGJA amongst the nine treatment regimens, which provided clinical guidance for clinicians in the treatment of EGJA.
On the anatomy of social engineering attacks—A literature‐based dissection of successful attacks
Authors: Bullée Jan‐Willem Hendrik , Montoya Lorena , Pieters Wolter , Junger Marianne , Hartel Pieter 
Published: July 2017

AbstractThe aim of this study was to explore the extent to which persuasion principles are used in successful social engineering attacks. Seventy‐four scenarios were extracted from 4 books on social engineering (written by social engineers) and analysed. Each scenario was split into attack steps, containing single interactions between offender and target. For each attack step, persuasion principles were identified. The main findings are that (a) persuasion principles are often used in social engineering attacks, (b) authority (1 of the 6 persuasion principles) is used considerably more often than others, and (c) single‐principle attack steps occur more often than multiple‐principle ones. The social engineers identified in the scenarios more often used persuasion principles compared to other social influences. The scenario analysis illustrates how to exploit the human element in security. The findings support the view that security mechanisms should include not only technical but also social countermeasures.
Three‐Dimensional Power Doppler Evaluation of Cerebral Vascular Blood Flow: A Novel Tool in the Assessment of Fetal Growth Restriction
Authors: Goetzinger Katherine R. , Cahill Alison G. , Odibo Linda , Macones George A. , Odibo Anthony O. 
Published: July 2017

ObjectivesTo determine whether fetuses with fetal growth restriction (FGR) are more likely to have abnormal cerebral vascular flow patterns compared to fetuses who are appropriate for gestational age (AGA) when quantified by using 3‐dimensional (3D) power Doppler ultrasound.MethodsWe conducted a prospective cohort study of singleton gestations presenting for growth ultrasound examination between 24 and 36 weeks' gestation. Patients with FGR (estimated fetal weight < 10th percentile) were enrolled and matched 1:1 for gestational age (±7 days) with AGA fetuses. A standardized 3D power Doppler image of the middle cerebral artery territory was obtained from each patient. The vascularization index (VI), flow index (FI), and vascularization‐flow index (VFI) were calculated by the Virtual Organ computer‐aided analysis technique (GE Healthcare, Milwaukee, WI). These indices were compared between FGR and AGA fetuses and correlated with 2‐dimensional Doppler parameters. Neonatal outcomes were also compared with respect to the 3D parameters.ResultsOf 306 patients, there were 151 cases of FGR. There was no difference in the VI (6.0 versus 5.7; P = .65) or VFI (2.0 versus 1.8; P = .31) between the groups; however, the FI was significantly higher in FGR fetuses compared to AGA controls (33.9 versus 32.3; P = .009). There was a weak, but significant, negative correlation between the FI and both the middle cerebral artery pulsatility index (r = −0.34; P < .001) and cerebroplacental ratio (r = −0.29; P < .001). Within the FGR group, there was no difference in any of the 3D vascular indices with regard to neonatal outcomes.ConclusionsThree‐dimensional power Doppler measurement of cerebral blood flow, but not the vascularization pattern, is significantly altered in FGR. This measurement may play a future role in distinguishing pathologic FGR from constitutionally small growth.
Neutron crystallographic studies of T4 lysozyme at cryogenic temperature
Authors: Li Le , Shukla Shantanu , Meilleur Flora , Standaert Robert F. , Pierce Josh , Myles Dean A. A. , Cuneo Matthew J. 
Published: July 2017

AbstractBacteriophage T4 lysozyme (T4L) has been used as a paradigm for seminal biophysical studies on protein structure, dynamics, and stability. Approximately 700 mutants of this protein and their respective complexes have been characterized by X‐ray crystallography; however, despite the high resolution diffraction limits attained in several studies, no hydrogen atoms were reported being visualized in the electron density maps. To address this, a 2.2 Å‐resolution neutron data set was collected at 80 K from a crystal of perdeuterated T4L pseudo‐wild type. We describe a near complete atomic structure of T4L, which includes the positions of 1737 hydrogen atoms determined by neutron crystallography. The cryogenic neutron model reveals explicit detail of the hydrogen bonding interactions in the protein, in addition to the protonation states of several important residues.
Prognostic accuracy of cerebroplacental ratio and middle cerebral artery Doppler for adverse perinatal outcome: systematic review and meta‐analysis
Authors: Vollgraff Heidweiller‐Schreurs C. A. , De Boer M. A. , Heymans M. W. , Schoonmade L. J. , Bossuyt P. M. M. , Mol B. W. J. , De Groot C. J. M. , Bax C. J. 
Published: July 2017

ABSTRACTObjectiveDoppler ultrasonographic assessment of the cerebroplacental ratio (CPR) and middle cerebral artery (MCA) is widely used as an adjunct to umbilical artery (UA) Doppler to identify fetuses at risk of adverse perinatal outcome. However, reported estimates of its accuracy vary considerably. The aim of this study was to review systematically the prognostic accuracies of CPR and MCA Doppler in predicting adverse perinatal outcome, and to compare these with UA Doppler, in order to identify whether CPR and MCA Doppler evaluation are of added value to UA Doppler.MethodsPubMed, EMBASE, the Cochrane Library and
ClinicalTrials.gov were searched, from inception to June 2016, for studies on the prognostic accuracy of UA Doppler compared with CPR and/or MCA Doppler in the prediction of adverse perinatal outcome in women with a singleton pregnancy of any risk profile. Risk of bias and concerns about applicability were assessed using the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies‐2) tool. Meta‐analysis was performed for multiple adverse perinatal outcomes. Using hierarchal summary receiver–operating characteristics meta‐regression models, the prognostic accuracy of CPR vs MCA Doppler was compared indirectly, and CPR and MCA Doppler vs UA Doppler compared directly.ResultsThe search identified 4693 articles, of which 128 studies (involving 47 748 women) were included. Risk of bias or suboptimal reporting was detected in 120/128 studies (94%) and substantial heterogeneity was found, which limited subgroup analyses for fetal growth and gestational age. A large variation was observed in reported sensitivities and specificities, and in thresholds used. CPR outperformed UA Doppler in the prediction of composite adverse outcome (as defined in the included studies) (P < 0.001) and emergency delivery for fetal distress (P = 0.003), but was comparable to UA Doppler for the other outcomes. MCA Doppler performed significantly worse than did UA Doppler in the prediction of low Apgar score (P = 0.017) and emergency delivery for fetal distress (P = 0.034). CPR outperformed MCA Doppler in the prediction of composite adverse outcome (P < 0.001) and emergency delivery for fetal distress (P = 0.013).ConclusionCalculating the CPR with MCA Doppler can add value to UA Doppler assessment in the prediction of adverse perinatal outcome in women with a singleton pregnancy. However, it is unclear to which subgroup of pregnant women this applies. The effectiveness of the CPR in guiding clinical management needs to be evaluated in clinical trials. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Zelltherapie am Augenhintergrund – gestern, heute, morgen
Authors: Brandl Caroline 
Published: July 2017

Zusammenfassung
Der gemeinsame Endpunkt vieler Netzhautdegenerationen ist ein Zelluntergang im retinalen Pigmentepithel und/oder der neurosensorischen Retina und ein damit verbundener irreversibler Visusverlust. Therapieansätze in fortgeschrittenen Erkrankungsstadien müssen folglich ebenfalls den Ersatz dieser verloren gegangenen Zellen und Gewebe adressieren. Hier zeichnen sich in den letzten Jahren vor allem auf dem Gebiet der stammzellbasierten zellulären Transplantationstherapie rasante Fortschritte in Grundlagenforschung und klinischer Anwendung ab. Besonders die induzierten pluripotenten Stammzellen scheinen die personalisierte Medizin signifikant voranbringen zu können, falls es gelingt wesentliche Bedenken und Limitationen zu überwinden. Diese Übersicht benennt retinale Krankheitsbilder, bei denen Zelltherapie eine potenzielle Therapieoption darstellt, und gibt einen kurzen Einblick in bisherige Therapiemöglichkeiten. Darüber hinaus werden insbesondere die potenziellen Anwendungsbereiche induzierter pluripotenter Stammzellen mit ihren Vorteilen, aber auch Problemen beleuchtet. Der Hauptfokus liegt auf dem stammzellbasierten Ersatz des retinalen Pigmentepithels, da dieser im Hinblick auf eine therapeutische Anwendung am Menschen, im Vergleich zu anderen Zellen der neurosensorischen Netzhaut, die größten Fortschritte verzeichnet. Abschließend wird ein Überblick über bereits laufende klinische Studien zur Therapie von Netzhautdegenerationen mittels stammzellbasierter zellulärer Transplantationstherapie gegeben.
Dueling, Conflicting Masculinities, and the Victorian Gentleman
Authors: Masterson Margery 
Published: July 2017

AbstractThis article takes an unexplored popular debate from the 1860s over the role of dueling in regulating gentlemanly conduct as the starting point to examine the relationship between elite Victorian masculinities and interpersonal violence. In the absence of a meaningful replacement for dueling and other ritualized acts meant to defend personal honor, multiple modes of often conflicting masculinities became available to genteel men in the middle of the nineteenth century. Considering the security fears of the period––European and imperial, real and imagined––the article illustrates how pacific and martial masculine identities coexisted in a shifting and uneasy balance. The professional character of the enlarging gentlemanly classes and the increased importance of men's domestic identities––trends often aligned with hegemonic masculinity––played an ambivalent role in popular attitudes to interpersonal violence. The cultural history of dueling can thus inform a multifaceted approach toward gender, class, and violence in modern Britain.