bluuebunny/crossref_metadata_2025_split huggingface dataset:
In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles
Authors: Eitan Erez , Tosti Valeria , Suire Caitlin N. , Cava Edda , Berkowitz Sean , Bertozzi Beatrice , Raefsky Sophia M. , Veronese Nicola , Spangler Ryan , Spelta Francesco , Mustapic Maja , Kapogiannis Dimitrios , Mattson Mark P. , Fontana Luigi 
Published: September 2017

SummaryObesity, metabolic syndrome, and hyperleptinemia are associated with aging and age‐associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans.
Interobserver Agreement in Pediatric Cervical Spine Injury Assessment Between Prehospital and Emergency Department Providers
Authors: Browne Lorin R. , Schwartz Hamilton , Ahmad Fahd A. , Wallendorf Michael , Kuppermann Nathan , Lerner E. Brooke , Leonard Julie C. 
Published: September 2017

AbstractBackgroundInvestigators have derived cervical spine injury (CSI) decision support tools from physician observations. There is a need to demonstrate that prehospital emergency medical services (EMS) providers can use these tools to appropriately determine the need for spinal motion restrictions and make field disposition decisions.ObjectivesThe objective was to determine the interobserver agreement between EMS and emergency department (ED) providers for CSI risk assessment variables and overall gestalt for CSI in children after blunt trauma.MethodsThis was a planned, substudy of a four‐site, prospective cohort of children < 18 years transported by EMS to pediatric EDs for evaluation of CSI after blunt trauma. Inclusion criteria were trauma team activation and/or EMS‐initiated spinal motion restriction. Exclusion criteria were penetrating trauma, transfer to another facility for definitive care, state custody, or substantial language barrier. For each eligible child, the transporting EMS provider and treating ED provider independently recorded their clinical assessment for CSI. This included mechanism of injury and patient history and physical examination findings. We assessed each paired variable for interobserver agreement between EMS and ED provider using kappa (κ) analysis. We considered variables with κ lower confidence interval values ≥0.4 to have moderate or better agreement.ResultsWe obtained 1,372 paired observations for 29 variables. After finding prevalence and observer bias were adjusted for, all variables achieved moderate to better agreement including eight variables previously shown to be independently associated with CSI in children: diving mechanism, high‐risk motor vehicle collision, altered mental status, focal neurologic findings, neck pain, torticollis, substantial torso injury, and predisposing medical condition. EMS and ED providers, however, showed less than moderate agreement for their overall gestalt for CSI in children. Of note, both EMS and ED providers did not assess for neck pain, inability to move the neck, and/or cervical spine tenderness in more than 10% of study patients.ConclusionsEmergency medical services and ED providers achieved at least moderate agreement in the assessment of CSI risk factors in children after blunt trauma. However, EMS and ED providers did not achieve moderate agreement on gestalt for CSI and some risk factors went unassessed by providers. These findings support the development of a pediatric CSI risk assessment tool for EMS and ED providers to reduce interventions for those children at very low risk for CSIs while still identifying all children with injury.
Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog‐Stimulated Stem Cell Antigen‐1 Positive Progenitor Stem Cell Expansion
Authors: Fitzpatrick Emma , Han Xu , Liu Weimin , Corcoran Eoin , Burtenshaw Denise , Morrow David , Helt Jay‐Christian , Cahill Paul A. , Redmond Eileen M. 
Published: September 2017

BackgroundCell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate ethanol (EtOH) on sonic hedgehog (SHh) signaling in regulating possible stem cell antigen‐1 positive (Sca1+) progenitor stem cell involvement during pathologic arterial remodeling.MethodsPartial ligation or sham operation of the left carotid artery was performed in transgenic Sca1‐enhanced green fluorescent protein (eGFP) mice gavaged with or without “daily moderate” EtOH.ResultsThe EtOH group had reduced adventitial thickening and less neointimal formation, compared to ligated controls. There was expansion of eGFP‐expressing (i.e., Sca1+) cells in remodeled vessels postligation (day 14), especially in the neo intima. EtOH treatment reduced the number of Sca1+ cells in ligated vessel cross‐sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 and Gli2, and RT–PCR of whole‐vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1‐eGFP mice with the SHh signaling inhibitor cyclopamine diminished SHh target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh‐induced differentiation to vascular smooth muscle cells.ConclusionsEtOH reduces SHh‐responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.
Influence of Cocaine‐Related Images and Alcohol Administration on Inhibitory Control in Cocaine Users
Authors: Pike Erika , Marks Katherine R. , Stoops William W. , Rush Craig R. 
Published: September 2017

BackgroundAlcohol use and impulsivity, including decreased inhibitory control, predict poor treatment outcomes for individuals with cocaine use disorders. This study sought to determine the effects of alcohol administration on inhibitory control following cocaine‐related and neutral cues on the Attentional Bias‐Behavioral Activation (ABBA) task in cocaine users. We hypothesized that the proportion of inhibitory failures would increase following cocaine, compared to neutral, cues. We further hypothesized that there would be an interaction between alcohol administration and task version, such that alcohol would impair inhibitory control following cocaine, but not neutral cues.MethodsFifty current cocaine users completed this mixed‐model, double‐blind, placebo‐controlled, crossover study over 2 experimental sessions. The ABBA task was completed following alcohol administration (0.0 and 0.65 g/kg). Subject‐rated drug effect and physiological measures were collected prior to and after alcohol administration.ResultsProportion of inhibitory failures was increased following cocaine‐related cues compared to neutral cues independent of alcohol dose. Alcohol administration also produced prototypical subject‐rated drug effects.ConclusionsA better understanding of the relationship between alcohol consumption and inhibitory control in cocaine users could direct the development of interventions to decrease the risk of relapse in individuals who drink and display impaired inhibitory control.
Comparison of the percentages of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia
Authors: El‐Chennawi Farha , Rageh Ibrahim Mohamed , Mansour Amira Ibrahim , Darwish Mohammed Ibrahim , Elghzaly Ashraf Antar , Sakr Basma El Sayed , Elbaz Khaled Mohsen 
Published: September 2017

ProblemLittle is known about how preeclampsia affects regulatory T‐cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.Method of studyThe percentage of umbilical cord blood CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs were analyzed by flow cytometry.ResultsCD4+ CD25high FOXP3+ Treg (%) and CD4+ FOXP3+ Treg (%) were significantly lower, while CD4+ CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers.ConclusionPreeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+ CD25high FOXP3+) in the umbilical cord blood of babies born to preeclamptic mothers.
Undifferentiated connective tissue diseases and adverse pregnancy outcomes. An undervalued association?
Authors: Spinillo Arsenio , Beneventi Fausta , Caporali Roberto , Ramoni Veronique , Montecucco Carlomaurizio 
Published: September 2017

Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well‐known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.
Safety and efficacy of intravenous iron polymaltose, iron sucrose and ferric carboxymaltose in pregnancy: A systematic review
Authors: Qassim Alaa , Mol Ben W. , Grivell Rosalie M. , Grzeskowiak Luke E. 
Published: September 2017

BackgroundIntravenous (IV) iron in pregnancy is useful where oral iron is not tolerated or a rapid replenishment of iron is required.AimsTo review the literature on the efficacy and safety of different IV iron preparations in the management of antenatal iron‐deficiency anaemia (IDA).Materials and methodsWe searched MEDLINE, Embase and Scopus from inception to June 2016. Eligible studies were randomised controlled trials (RCTs) and observational studies, involving administration of IV iron (ferric carboxymaltose (FCM), iron polymaltose (IPM) or iron sucrose (IS)), regardless of comparator, to manage antenatal IDA. Two independent reviewers selected studies, extracted data and assessed quality.ResultsA total of 47 studies were eligible (21 RCTs and 26 observational studies), investigating IS (n = 2635; 41 studies), FCM (n = 276; four studies) and IPM (n = 164; three studies). All IV preparations resulted in significant improvements in haematological parameters, with a median increase of 21.8 g/L at 3–4 weeks and 30.1 g/L by delivery, but there was no evidence of any associated improvements in clinical outcomes. A greater median increase in Hb was observed with a high (25 g/L; range: 20–39.6 g/L) compared with low dose (20 g/L; range: 6.2–50.3 g/L). The median prevalence of adverse drug reactions for IPM (2.2%; range: 0–4.5%) was lower than FCM (5.0%; range: 0–20%) and IS (6.7%; range: 0–19.5%).ConclusionWhile IV iron in pregnancy improves haematological parameters, there is an absence of evidence for improvements in important maternal or perinatal outcomes. No single preparation of IV iron appeared to be superior, with the current IV iron preparation of choice largely determined by cost and convenience around administration.
Myocardial bridging is associated with exercise‐induced ventricular arrhythmia and increases in QT dispersion
Authors: Nishikii‐Tachibana Makiko , Pargaonkar Vedant S. , Schnittger Ingela , Haddad Francois , Rogers Ian S. , Tremmel Jennifer A. , Wang Paul J. 
Published: September 2017

BackgroundA myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort.MethodsWe studied the rest and stress ECG tracings of patients with an MB suspected by focal septal buckling on exercise echocardiography (EE) (Echo‐MB group, N = 510), those with an MB confirmed by another examination (MB group, N = 110), and healthy controls (Control group, N = 198).ResultsThe frequency of exercise‐induced premature ventricular contractions (PVCs) was significantly higher in the Echo‐MB and MB groups compared with the Control group (both p < .001). In all, 25 patients (4.9%) in the Echo‐MB group, seven patients (6.4%) in the MB group and no patients in the Control group had exercise‐induced non‐sustained ventricular tachycardia (NSVT). There was no difference in the baseline QTd between the groups. In the Echo‐MB and MB groups, QTd postexercise increased significantly when compared with baseline (both p < .001). Patients with NSVT had a higher frequency of male gender and an even greater increase in QTd with exercise compared with the non‐NSVT group.DiscussionThere is an increased frequency of exercise‐induced PVCs and NSVT in patients with MBs. Exercise significantly increases QTd in MB patients, with an even greater increase in QTd in MB patients with NSVT. Exercise in MB patients results in ventricular arrhythmias and abnormalities in repolarization.
Fetal microchimerism in human brain tumors
Authors: Broestl Lauren , Rubin Joshua B. , Dahiya Sonika 
Published: September 2017

AbstractSex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal‐in‐maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively.
Cancer‐specific mortality of high‐risk prostate cancer after carbon‐ion radiotherapy plus long‐term androgen deprivation therapy
Authors: Kasuya Goro , Ishikawa Hitoshi , Tsuji Hiroshi , Haruyama Yasuo , Kobashi Gen , Ebner Daniel K. , Akakura Koichiro , Suzuki Hiroyoshi , Ichikawa Tomohiko , Shimazaki Jun , Makishima Hirokazu , Nomiya Takuma , Kamada Tadashi , Tsujii Hirohiko ,   the Working Group for Genitourinary Tumors
Published: September 2017

The treatment outcomes of patients with high‐risk localized prostate cancer (PC) after carbon‐ion radiotherapy (CIRT) combined with long‐term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC‐specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed‐dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high‐risk or very‐high‐risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow‐up time was 88.4 months, and the 5‐/10‐year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9–10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10‐year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10‐year follow‐up (10‐year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high‐risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high‐risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high‐risk PC patients treated with CIRT.
Genetic trade‐off: Resistance to malaria or susceptibility to multiple sclerosis
Authors: Ochi Hirofumi 
Published: September 2017

AbstractMany types of genetic variations have evolved in humans as a result of evolutionary adaptation to malaria. Steri et al. reported that a genetic variant that provided resistance to Plasmodium falciparum or Plasmodium vivax malaria might have increased the susceptibility to multiple sclerosis among Sardinians.
Quarantine, isolation and the duty of easy rescue in public health
Authors: Giubilini Alberto , Douglas Thomas , Maslen Hannah , Savulescu Julian 
Published: September 2017

AbstractWe address the issue of whether, why and under what conditions, quarantine and isolation are morally justified, with a particular focus on measures implemented in the developing world. We argue that the benefits of quarantine and isolation justify some level of coercion or compulsion by the state, but that the state should be able to provide the strongest justification possible for implementing such measures. While a constrained form of consequentialism might provide a justification for such public health interventions, we argue that a stronger justification is provided by a principle of State Enforced Easy Rescue: a state may permissibly compel individuals to engage in activities that entail a small cost to them but a large benefit to others, because individuals have a moral duty of easy rescue to engage in those activities. The principle of State Enforced Easy Rescue gives rise to an Obligation Enforcement Requirement: the state should create the conditions such that submitting to coercive or compulsive measures becomes a fundamental moral duty of individuals, i.e. a duty of easy rescue. When the state can create such conditions, it has the strongest justification possible for implementing coercive or compulsive measures, because individuals have a moral duty to temporarily relinquish the rights that such measures would infringe. Our argument has significant implications for how public health emergencies in the developing world should be tackled. Where isolation and quarantine measures are necessary, states or the international community have a moral obligation to provide certain benefits to those quarantined or isolated.
Reconciling female genital circumcision with universal human rights
Authors: Gordon John‐Stewart 
Published: September 2017

AbstractOne of the most challenging issues in cross‐cultural bioethics concerns the long‐standing socio‐cultural practice of female genital circumcision (FGC), which is prevalent in many African countries and the Middle East as well as in some Asian and Western countries. It is commonly assumed that FGC, in all its versions, constitutes a gross violation of the universal human rights of health, physical integrity, and individual autonomy and hence should be abolished. This article, however, suggests a mediating approach according to which one form of FGC, the removal of the clitoris foreskin, can be made compatible with the high demands of universal human rights. The argument presupposes the idea that human rights are not absolutist by nature but can be framed in a meaningful, culturally sensitive way. It proposes important limiting conditions that must be met for the practice of FGC to be considered in accordance with the human rights agenda.