bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes derived from exhausted CD8+ T cells impaired the anticancer function of normal CD8+ T cells
Authors: Wang Xiaochen , Shen Haiyuan , He Qifeng , Tian Wenfang , Xia Anliang , Lu Xiao-Jie 
Published: July 2018

BackgroundPrevious studies suggested that diverse cells in cancer microenvironment can interact with CD8+ T cells via exosomes. We designed this study to explore the potential interaction between exhausted CD8+ T cells and normal CD8+ T cells via exosome.MethodsFluorescence activated cell sorting was used to get PD1+TIM3+/PD1−TIM3−CD8+ T cells. Exosomes from the cell culture medium were collected by ultracentrifugation. Microarrays were performed to analyse the lncRNA expression profile in exosomes.ResultsFunctional exhausted CD8+ T cells could secrete vast exosomes, which can be uptake by normal CD8+ T cells, and impaired their proliferation (Ki67), cell activity (CD69) and the production of cytokines such as interferon-γ and interleukin-2. Microarray detection identified 257 candidate lncRNAs differently expressed in exosomes derived from exhausted CD8+ T cells and non-exhausted CD8+ T cells. Functional enrichment analysis indicated that these lncRNAs actively participated in the regulation of diverse process of CD8+ T cell activity, like metabolism, gene expression, biosynthetic process and so forth.ConclusionsThe exosomes derived from exhausted CD8+ T cells could be uptake by non-exhausted CD8+ T cells and subsequently impaired the function of receipt cells. Exosomes secreted from exhausted CD8+ T cells have distinct lncRNA expression profiles which are significantly different from those in exosomes secreted by non-exhausted CD8+ T cells.
Altered Cell-Cycle Control, Inflammation, and Adhesion in High-Risk Persistent Bronchial Dysplasia
Authors: Merrick Daniel T. , Edwards Michael G. , Franklin Wilbur A. , Sugita Michio , Keith Robert L. , Miller York E. , Friedman Micah B. , Dwyer-Nield Lori D. , Tennis Meredith A. , O'Keefe Mary C. , Donald Elizabeth J. , Malloy Jessica M. , van Bokhoven Adrie , Wilson Storey , Koch Peter J. , O'Shea Charlene , Coldren Christopher , Orlicky David J. , Lu Xian , Baron Anna E. , Hickey Greg , Kennedy Timothy C. , Powell Roger , Heasley Lynn , Bunn Paul A. , Geraci Mark , Nemenoff Raphael A. 
Published: July 2018

Abstract
Persistent bronchial dysplasia is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive bronchial dysplasia would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes [ANOVA, FDR ≤ 0.05). Thirty-one pathways showed significantly altered activity between the two groups, many of which were associated with cell-cycle control and proliferation, inflammation, or epithelial differentiation/cell–cell adhesion. Cultured persistent bronchial dysplasia cells exhibited increased expression of Polo-like kinase 1 (PLK1), which was associated with multiple cell-cycle pathways. Treatment with PLK1 inhibitor induced apoptosis and G2–M arrest and decreased proliferation compared with untreated cells; these effects were not seen in normal or regressive bronchial dysplasia cultures. Inflammatory pathway activity was decreased in persistent bronchial dysplasia, and the presence of an inflammatory infiltrate was more common in regressive bronchial dysplasia. Regressive bronchial dysplasia was also associated with trends toward overall increases in macrophages and T lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of bronchial dysplasia. These results identify alterations in the persistent subset of bronchial dysplasia that are associated with high risk for progression to invasive SCC. These alterations may serve as strong markers of risk and as effective targets for lung cancer prevention.
Significance: Gene expression profiling of high-risk persistent bronchial dysplasia reveals changes in cell-cycle control, inflammatory activity, and epithelial differentiation/cell–cell adhesion that may underlie progression to invasive SCC. Cancer Res; 78(17); 4971–83. ©2018 AACR.
Nephron‐Specific Disruption of Nitric Oxide Synthase 3 Causes Hypertension and Impaired Salt Excretion
Authors: Gao Yang , Stuart Deborah , Takahishi Takamune , Kohan Donald E. 
Published: July 2018

Background

In vitro studies suggest that nephron nitric oxide synthase 3 (
NOS
3) modulates tubule Na
+
transport.

Methods and Results

To assess nephron
NOS
3 relevance in vivo, knockout (KO) mice with doxycycline‐inducible nephron‐wide deletion of
NOS
3 were generated. During 1 week of salt loading,
KO
mice, as compared with controls, had higher arterial pressure and Na
+
retention, a tendency towards reduced plasma renin concentration, and unchanged glomerular filtration rate. Chronic high salt‐treated
KO
mice had modestly decreased total
NCC
and total
SPAK
/
OSR
1 versus controls, however percent phosphorylation of
NCC
(at T
53
) and of
SPAK
/
OSR
1 was increased. In contrast, total and phosphorylated
NKCC
2 (at T
96/101
) were suppressed by 50% each in
KO
versus control mice after chronic salt intake. In response to an acute salt load,
KO
mice had delayed urinary Na
+
excretion versus controls; this delay was completely abolished by furosemide, partially reduced by hydrochlorothiazide, but not affected by amiloride. After 4 hours of an acute salt load, phosphorylated and total
NCC
were elevated in
KO
versus control mice. Acute salt loading did not alter total
NKCC
2 or
SPAK
/
OSR
1 in
KO
versus control mice but increased the percent phosphorylation of
NKCC
2 (at T
96/101
and S
126
) and
SPAK
/
OSR
1 in
KO
versus control mice.

Conclusions

These findings indicate that nephron
NOS
3 is involved in blood pressure regulation and urinary Na
+
excretion during high salt intake. Nephron
NOS
3 appears to regulate
NKCC
2 and
NCC
primarily during acute salt loading. These effects of
NOS
3 may involve
SPAK
/
OSR
1 as well as other pathways.
‘Home, Sweet Home’: Managing Returning Foreign Terrorist Fighters in Germany, The United Kingdom and Australia
Authors: Braun Kerstin 
Published: July 2018

Abstract
Since 2011, the conflict in Syria and Iraq has seen unprecedented numbers of Westerners travelling to the region to support jihadist terror organisations, so-called Foreign Terrorist Fighters (‘FTFs’). However, since 2015, with Islamic State’s financial and territorial losses, the numbers of Western FTFs are dwindling and many are returning to their countries of origin. As a consequence, numerous countries are grappling with how to best manage potential security threats arising from returning FTFs. This article critically analyses legal and criminal justice strategies to address this phenomenon implemented in three Western countries from which a significant number of FTFs originate: Germany, the United Kingdom and Australia. It focuses on prosecution, prevention of re-entry and rehabilitation of returning FTFs. It suggests that a holistic approach focusing on punitive but also on de-radicalising and reintegrating measures is best suited to address the security risks FTFs pose long term.
Prevalence and correlates of psychotic experiences in a nationally representative sample of Australian adolescents
Authors: Hielscher Emily , Connell Melissa , Lawrence David , Zubrick Stephen R , Hafekost Jennifer , Scott James G 
Published: July 2018

Objective: Despite growing literature on psychotic experiences, no nationally representative study has reported on the prevalence of both hallucinatory experiences and delusional experiences in Australian adolescents. Also, while many studies have examined the association between psychotic experiences and certain demographic and clinical correlates, there are more variables of interest to be investigated, including disordered eating behaviour and hours of sleep. The aims of this study were to examine (1) the prevalence of hallucinatory experiences and delusional experiences in Australian adolescents, and (2) the associations between different types of psychotic experiences with a broad range of demographic, clinical, and psychosocial variables. Methods: A random sample of Australian adolescents aged 14- to 17-year-olds were recruited in 2013–2014 as part of the Young Minds Matter Survey. Participants completed self-report questions regarding five different psychotic experience types (auditory and visual hallucinatory experiences, and thoughts read, special messages, spied upon) experienced in the past 12 months. Using logistic regression analyses, we investigated associations between psychotic experiences and demographic, clinical, and psychosocial factors. Results: The 12-month prevalence ranged from 3.3% (95% confidence interval = [2.6, 4.3]) for special messages to 14.0% (95% confidence interval = [12.3, 15.8]) for auditory hallucinatory experiences. At the bivariate level, each psychotic experience subtype was associated with increased likelihood of major depression, being bullied, psychological distress, low self-esteem, mental health service use and insufficient sleep (<8 hours per night). Multivariate analyses revealed both auditory and visual hallucinatory experiences were associated with an increased likelihood of four of these variables (depression, being bullied, service use, insufficient sleep), whereas associations with delusional experiences were inconsistent. Conclusion: Hallucinatory and delusional experiences are common in Australian adolescents. Hallucinatory experiences, rather than delusional experiences, may be more clinically relevant in this demographic. When psychotic experiences are endorsed by adolescents, further assessment is indicated so as to ascertain more detail on the phenomenology of the experiences to better understand their clinical relevance.
Measuring and Mitigating the Costs of Attentional Switches in Active Network Monitoring for Cybersecurity
Authors: Kortschot Sean W. , Sovilj Dusan , Jamieson Greg A. , Sanner Scott , Carrasco Chelsea , Soh Harold 
Published: July 2018

Objective: The authors seek to characterize the behavioral costs of attentional switches between points in a network map and assess the efficacy of interventions intended to reduce those costs. Background: Cybersecurity network operators are tasked with determining an appropriate attentional allocation scheme given the state of the network, which requires repeated attentional switches. These attentional switches may result in temporal performance decrements, during which operators disengage from one attentional fixation point and engage with another. Method: We ran two experiments where participants identified a chain of malicious emails within a network. All interactions with the system were logged and analyzed to determine if users experienced disengagement and engagement delays. Results: Both experiments revealed significant costs from attentional switches before (i.e., disengagement) and after (i.e., engagement) participants navigated to a new area in the network. In our second experiment, we found that interventions aimed at contextualizing navigation actions lessened both disengagement and engagement delays. Conclusion: Attentional switches are detrimental to operator performance. Their costs can be reduced by design features that contextualize navigations through an interface. Application: This research can be applied to the identification and mitigation of attentional switching costs in a variety of visual search tasks. Furthermore, it demonstrates the efficacy of noninvasive behavioral monitoring for inferring cognitive events.
Impact of age on early outcomes and long-term survival of patients undergoing aortic repair with Stanford A dissection
Authors: Merkle Julia , Sabashnikov Anton , Weber Carolyn , Schlachtenberger Georg , Maier Johanna , Spieker Anna , Eghbalzadeh Kaveh , Deppe Antje-Christin , Zeriouh Mohamed , Rahmanian Parwis B. , Madershahian Navid , Rustenbach Christian , Choi Yeong-Hoon , Kuhn-Régnier Ferdinand , Liakopoulos Oliver , Wahlers Thorsten 
Published: July 2018

Objectives: Stanford A acute aortic dissection (AAD) is a life-threatening emergency, typically occurring in older patients and requiring immediate surgical repair. The aim of this study was to evaluate early outcome and short- and long-term survival of patients under and above 65 years of age. Methods: Two hundred and forty patients with Stanford A AAD underwent aortic surgical repair from January 2006 to April 2015 in our center. After statistical analysis and logistic regression analysis, Kaplan-Meier survival estimation was performed, with up to 9-year follow-up, comprising patients under and above 65 years of age. Results: The proportion of patients above 65 years of age suffering from Stanford A AAD was 50% (n=120). The group of patients above 65 years of age compared to the group under 65 years of age showed statistically significant differences in terms of higher odds ratios (OR) for hypertension (p=0.012), peripheral vascular disease (p=0.026) and tachyarrhythmia absoluta (p=0.004). Patients over 65 years of age also showed significantly poorer short- and long-term survival. Our subgroup analysis revealed that male patients (Breslow p=0.001, Log-Rank p=0.001) and patients suffering with hypertension (Breslow p=0.003, Log-Rank p=0.001) were reasonable for these results whereas younger and older female patients showed similar short- and long-term outcome (Breslow p=0.926, Log-Rank p=0.724). After stratifying all patients into 4 age groups (<45; 55-65; 65-75; >75years), short-term survival of the patients appeared to be significantly poorer with increasing age (Breslow p=0.026, Log-Rank p=0.008) whereas long-term survival of patients free from cerebrovascular events (Breslow p=0.0494, Log-Rank p=0.489) remained similar. Conclusions: All patients referred to our hospital for repair of Stanford A AAD with higher age had poorer short- and long-term survival, caused by male patients and patients suffering from hypertension, whereas survival of women and survival free from cerebrovascular events of the entire patient cohort was similar, irrespective of age.
Internal Fixation of Unstable Osteochondritis Dissecans: Do Open Growth Plates Improve Healing Rate?
Authors: Wu Isabella T. , Custers Roel J.H. , Desai Vishal S. , Pareek Ayoosh , Stuart Michael J. , Saris Daniël B.F. , Krych Aaron J. 
Published: July 2018

Background: Osteochondritis dissecans (OCD) is a disorder of unknown origin that can affect knees in skeletally mature and immature patients. Surgical management is an important cornerstone of treatment for unstable OCD lesions. Purpose: To determine the (1) healing rate after internal fixation of unstable OCD between skeletally immature and mature knees, (2) risk factors for failure, and (3) patient-reported outcomes among healed patients. Study Design: Cohort study; Level of evidence, 3. Methods: A multicenter retrospective cohort study was conducted with patients who underwent internal fixation of unstable knee OCD lesions from 2000 to 2015. Skeletal immaturity was defined as open or partially open physes. Healing was assessed through clinical findings and imaging. Definitive reoperation for the same OCD lesion was classified as failure. Results: Among 87 patients included, 66 (76%) had healed lesions at ≥2 years postoperatively, while 21 (24%) failed. Skeletal maturity made no significant difference in failure rate (risk ratio, 0.68; 95% CI, 0.29-1.72; P = .40). For skeletally immature patients, lateral versus medial condylar location conferred an increased hazard of 18.2 (95% CI, 1.76-188.07; P < .01). Multivariate analysis factoring in skeletal maturity showed that lateral condylar location was an independent risk factor for failure (hazard ratio, 4.25; 95% CI, 1.47-19.85; P < .01). Mean patient-reported outcome scores (International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]) increased significantly after surgery, except the KOOS symptoms score for the skeletally mature group. Final scores (mean ± SD) were as follows at a mean follow-up of 60 months (range, 24-166): IKDC, 83.5 ± 20.2; KOOS pain, 89.7 ± 14.1; KOOS symptoms, 87.4 ± 18.4; KOOS activities of daily living, 93.9 ± 12.7; KOOS sports, 80.7 ± 25.9; KOOS quality of life, 78.9 ± 23.1. Conclusion: Skeletally immature and mature patients heal at comparable rates after internal fixation of OCD lesions, resulting in functional and subjective improvement. Lateral femoral condylar lesion location is an independent risk factor for failure.
A comparative clinical study on the generation of nitrosative stress in cataractous lenses of smokers and non-smoker tobacco patients
Authors: Anitha Thirugnanasambandhar Sivasubramanian , Srikanth Krishnagopal , Suganya Subrayan , Muthukumar Subramanian 
Published: July 2018

Aim: To quantify the levels of nitric oxide, inducible nitric oxide synthase, and 3-nitrotyrosine in cataractous lenses of smokers and smokers who chewed tobacco in comparison with non-smokers and non-smokers who chewed tobacco. Study design: A total of 80 cataractous lenses from smokers, non-smokers, smokers with tobacco chewing habit, and non-smokers with tobacco chewing habit were collected from the patients who had enrolled in the Department of Ophthalmology, Mahatma Gandhi Medical College & Research Institute, Puducherry. Methods: Levels of nitric oxide, inducible nitric oxide synthase, and 3-nitrotyrosine were quantified using commercially available enzyme-linked immunosorbent assay kits. Results: The mean concentrations of lens nitric oxide, inducible nitric oxide synthase, and 3-nitrotyrosine are as follows: (a) smokers—112.01, 59.57, and 88.91 µmol/L; (b) smokers who chewed tobacco—175.15, 93.95, and 128.72 µmol/L; (c) non-smokers—76.15, 40.65, and 70.20 µmol/L; and (d) non-smokers who chewed tobacco—96.56, 52.87, and 83.88 µmol/L, respectively. Conclusion: Nitric oxide, inducible nitric oxide synthase, and 3-nitrotyrosine at high levels are the major causative agents for cataractogenesis. The results of this study suggest that smoking and tobacco chewing habit generate nitrosative stress that could enhance the pathogenesis for early cataractogenesis.
NIHSS sub-item scores predict collateral flow in acute middle cerebral artery infarction
Authors: Hwang Jaechun , Lee Mi Ji , Chung Jong-Won , Bang Oh Young , Kim Gyeong-Moon , Chung Chin-Sang , Lee Kwang Ho 
Published: July 2018

Background and purpose The status of collateral vessels has important clinical implications in acute ischemic stroke. To evaluate which components of ischemic symptoms were predictive of pretreatment collateral status, we tested the hypothesis that sub-item scores from the National Institutes of Health Stroke Scale (NIHSS) are associated with leptomeningeal collateral status in acute ischemic stroke with middle cerebral artery (MCA) occlusion. Methods This study included consecutive patients with acute M1 occlusion who underwent revascularization treatment for acute MCA infarction. We evaluated clinical factors and the NIHSS score according to the collateral status assessed by multiphase perfusion computed tomography. Results Eighty-six patients were included (48 good collateral status, 38 poor collateral status). The patients with poor collateral status were more likely to have a higher total NIHSS score (18 versus 11, p < 0.001) and atrial fibrillation (65.8% versus 41.7%, p = 0.026) than patients with good collateral flow. In a multiple logistic regression, the NIHSS sub-items such as profound “facial palsy” (score 2 versus 0–1) and “visual field defect” (score 2 versus 0–1) were independently associated with poor collateral status. Conclusion Among the NIHSS sub-items, severe facial palsy and visual field defect were associated with poor collateral status in acute MCA stroke with M1 occlusion. Decision on whether to treat these patients endovascularly should be made more cautiously due to the possibility of a poor outcome.
Using Cluster Analysis to Understand Clinician Readiness to Promote Continuous Glucose Monitoring Adoption
Authors: Tanenbaum Molly L. , Adams Rebecca N. , Lanning Monica S. , Hanes Sarah J. , Agustin Bianca I. , Naranjo Diana , Hood Korey K. 
Published: July 2018

Background: Many people with type 1 diabetes (T1D) report barriers to using continuous glucose monitoring (CGM). Diabetes care providers may have their own barriers to promoting CGM uptake. The goal of this study was to develop clinician “personas” with regard to readiness to promote CGM uptake. Methods: Diabetes care providers who treat people with T1D (N = 209) completed a survey on perceived patient barriers to device uptake, technology attitudes, and characteristics and barriers specific to their clinical practice. K-means cluster analyses grouped the sample by CGM barriers and attitudes. ANOVAs and chi-square tests assessed group differences on provider and patient characteristics. The authors assigned descriptive names for each persona. Results: Analyses yielded three clinician personas regarding readiness to promote CGM uptake. Ready clinicians (20% of sample; 24% physicians, 38% certified diabetes educators/CDEs) had positive technology attitudes, had clinic time to work with patients using CGM, and found it easy to keep up with technology advances. In comparison, Cautious clinicians (41% of sample; 17% physicians, 53% CDEs) perceived that their patients had many barriers to adopting CGM and had less time than the Ready group to work with patients using CGM data. Not Yet Ready clinicians (40% of sample; 9% physicians; 79% CDEs) had negative technology attitudes and the least clinic time to work with CGM data. They found it difficult to keep up with technology advances. Conclusion: Some diabetes clinicians may benefit from tailored interventions and additional time and resources to empower them to help facilitate increased uptake of CGM technology.
Therapeutic vulnerability of multiple myeloma to MIR17PTi, a first-in-class inhibitor of pri-miR-17-92
Authors: Morelli Eugenio , Biamonte Lavinia , Federico Cinzia , Amodio Nicola , Di Martino Maria Teresa , Gallo Cantafio Maria Eugenia , Manzoni Martina , Scionti Francesca , Samur Mehmet Kemal , Gullà Annamaria , Stamato Maria Angelica , Pitari Maria Rita , Caracciolo Daniele , Sesti Settimio , Frandsen Niels M. , Rossi Marco , Neri Antonino , Fulciniti Mariateresa , Munshi Nikhil C. , Tagliaferri Pierosandro , Tassone Pierfrancesco 
Published: July 2018

Key Points
First-in-class MIR17PTi enables 1-shot downregulation of miR-17-92 in vitro and in vivo, with favorable pharmacokinetic profile. MIR17PTi affects homeostatic MYC/miR-17-92 FFLs in MM cells, resulting in strong anti-MM activity.