bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diseases transmission in a z-ary tree
Authors: Debs P. , Haberkorn T. 
Published: October 2016

Consider a Galton–Watson tree [Formula: see text] of height [Formula: see text], each leaf is either infected by one of [Formula: see text] diseases or not infected at all. In other words, [Formula: see text] at generation [Formula: see text] is infected by the [Formula: see text]th infection with probability [Formula: see text] and sane with probability [Formula: see text]. Moreover, the infections are independently distributed for each leaf. Infections spread along the tree based on deterministic specific rules. We study the limit distribution of the disease of the root of [Formula: see text] as [Formula: see text] goes to infinity. We also study the specific case of a [Formula: see text]-ary tree, and we prove convergence of the distribution of the root node for [Formula: see text].
A Novel Superoxide Anion Radical Nonenzymatic Electrochemical Sensor Based on PtRuCu Ternary Alloy Nanoparticles/Graphene Composite Modified Electrode
Authors: Ren Jujie , Zhai Miao , Cui Min , Li Liujia , Yu Congcong , Yu Xudong , Ji Xueping 
Published: October 2016

A superoxide anion radical (O[Formula: see text] nonenzymatic electrochemical sensor based on PtRuCu ternary alloy nanoparticles/electrochemically reduced graphene oxide (ERGO) composite modified glassy carbon electrode (PtRuCu/ERGO/GCE) was developed. ERGO and PtRuCu/ERGO composites were characterized by scanning electron microscopy. The prepared PtRuCu/ERGO/GCE showed remarkable performance toward the electrocatalytic reduction of (O[Formula: see text]. The sensor possessed a high sensitivity of 1725[Formula: see text]A[Formula: see text][Formula: see text][Formula: see text]mM[Formula: see text][Formula: see text]cm[Formula: see text], a wide linear range of 7.5–330[Formula: see text][Formula: see text]M ([Formula: see text]0.993) and a low detection limit of 0.7[Formula: see text][Formula: see text]M ([Formula: see text]/[Formula: see text]), as well as excellent selectivity, reproducibility and stability, which can be attributed to the synergistic effect of ERGO and PtRuCu ternary alloy nanoparticles. Therefore, the prepared sensor is promising for electrochemical determination of O[Formula: see text].
Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment
Authors: Liu Yang , Pandeswara Srilakshmi , Dao Vinh , Padrón Álvaro , Drerup Justin M. , Lao Shunhua , Liu Aijie , Hurez Vincent , Curiel Tyler J. 
Published: October 2016

AbstractmTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1–8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)–mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell–dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L+ CD8+ central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520–31. ©2016 AACR.
Thyroid Cancer: Risk-Stratified Management and Individualized Therapy
Authors: Raue Friedhelm , Frank-Raue Karin 
Published: October 2016

AbstractThyroid cancer is the most common endocrine malignancy. Differentiated thyroid cancer (DTC) with the two subtypes, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), is the most frequent subtype of thyroid cancer; more rare subtypes are medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC). The incidence of DTC has increased rapidly in recent years due to the more frequent use of imaging methods such as ultrasound of the neck and fine-needle aspiration (FNA) of thyroid nodules. After total thyroidectomy and radioiodine treatment, DTC remains an indolent and curable disease in most patients, whereas the cure rate in MTC is lower and depends on early diagnosis. Most ATCs are incurable. In recent years, there has been great progress in identifying genetic changes in thyroid cancer, and genetic testing of FNA samples or blood samples provides useful information for clinical decision making. Tumor staging, either postoperatively or by imaging, and measuring the tumor markers thyroglobulin for DTC and calcitonin for MTC, allow for dynamic risk-adapted stratification for follow-up procedures. In advanced metastatic thyroid cancer, molecular targeted therapy using tyrosine kinase receptor inhibitors, including sorafenib, lenvantinib, vandetanib, and cabozantinib, helps control tumor progression and prolongs progression-free survival. Using a dynamic risk-stratified approach to manage thyroid cancer, the outcomes for most thyroid cancer patients are excellent compared with those for other cancers. The major challenge in the future is to identify high-risk patients and to treat and monitor them appropriately. Clin Cancer Res; 22(20); 5012–21. ©2016 AACR.See all articles in this CCR Focus section, “Endocrine Cancers: Revising Paradigms.”
Pheochromocytoma: The First Metabolic Endocrine Cancer
Authors: Jochmanova Ivana , Pacak Karel 
Published: October 2016

Abstract
Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics has allowed us to take a closer look at the metabolic changes present in pheochromocytomas (PHEO) and paragangliomas (PGL). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOs/PGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies. Clin Cancer Res; 22(20); 5001–11. ©2016 AACR.
See all articles in this CCR Focus section, “Endocrine Cancers: Revising Paradigms.”
MicroRNA let-7, T Cells, and Patient Survival in Colorectal Cancer
Authors: Dou Ruoxu , Nishihara Reiko , Cao Yin , Hamada Tsuyoshi , Mima Kosuke , Masuda Atsuhiro , Masugi Yohei , Shi Yan , Gu Mancang , Li Wanwan , da Silva Annacarolina , Nosho Katsuhiko , Zhang Xuehong , Meyerhardt Jeffrey A. , Giovannucci Edward L. , Chan Andrew T. , Fuchs Charles S. , Qian Zhi Rong , Ogino Shuji 
Published: October 2016

Abstract
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis. Logistic regression analysis and Cox proportional hazards regression were used to assess associations of let-7a (and let-7b) expression (quartile predictor variables) with T-cell densities (binary outcome variables) and mortality, respectively, controlling for tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared with cases in the lowest quartile of let-7a expression, those in the highest quartile were associated with lower densities of CD3+ [multivariate odds ratio (OR), 0.40; 95% confidence interval (CI), 0.23–0.67; Ptrend = 0.003] and CD45RO+ cells (multivariate OR, 0.31; 95% CI, 0.17–0.58; Ptrend = 0.0004), and higher colorectal cancer-specific mortality (multivariate hazard ratio, 1.82; 95% CI, 1.42–3.13; Ptrend = 0.001). In contrast, let-7b expression was not significantly associated with T-cell density or colorectal cancer prognosis. Our data support the role of let-7a in suppressing antitumor immunity in colorectal cancer and suggest let-7a as a potential target of immunotherapy. Cancer Immunol Res; 4(11); 927–35. ©2016 AACR.
CXCR2-Dependent Accumulation of Tumor-Associated Neutrophils Regulates T-cell Immunity in Pancreatic Ductal Adenocarcinoma
Authors: Chao Timothy , Furth Emma E. , Vonderheide Robert H. 
Published: October 2016

AbstractTumor-associated neutrophils are increasingly recognized for their ability to promote tumor progression, mediate resistance to therapy, and regulate immunosuppression. Evidence from various murine models has shown that the chemokine receptor CXCR2 attracts neutrophil into tumors and, therefore, represents a tractable therapeutic target. Here, we report prominent expression of a neutrophil gene signature in a subset of human pancreatic adenocarcinoma (PDA). CXCL5 was the most prominently expressed CXCR2 ligand in human PDA, and its expression was higher in PDA than in any other common tumor represented in The Cancer Genome Atlas. Using a genetically engineered mouse model of PDA, we found that tumor and stromal cells differentially expressed CXCR2 ligands, with Cxcl5 high in tumor and Cxcl2 high in stroma. Cxcl5 expression was associated with mutant Kras expression and regulated by NF-κB activation. Host CXCR2 inhibition by genetic ablation prevented neutrophil accumulation in pancreatic tumors and led to a T cell–dependent suppression of tumor growth. In the absence of neutrophils, activated and functional T cells infiltrated pancreatic tumors otherwise devoid of effector T cells. Thus, the CXCR2–ligand axis helps establish an immunosuppressive microenvironment in PDA, highlighting the potential utility of targeting this axis as a novel therapy for this deadly disease. Cancer Immunol Res; 4(11); 968–82. ©2016 AACR.
Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack
Authors: Zhou Yilun , Pan Yuesong , Wu Yu , Zhao Xingquan , Li Hao , Wang David , Johnston S. Claiborne , Liu Liping , Wang Chunxue , Meng Xia , Wang Yilong , Wang Yongjun ,   on behalf of the CHANCE Investigators
Published: October 2016

Background and Purpose—
Patients with chronic kidney disease (CKD) are at a particularly high risk for ischemic and bleeding events. Limited data exist as to the efficacy and safety of clopidogrel in stroke patients with renal dysfunction. Therefore, we sought to assess the impact of decreased kidney function on clinical outcomes for stroke patients on clopidogrel–aspirin treatment.

Methods—
Patients in the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were randomized to clopidogrel–aspirin or aspirin-alone treatment. The primary efficacy outcome was new stroke during 90 days, whereas bleeding was the safety outcome. Patients were stratified according to estimated glomerular filtration rate.

Results—

Dual clopidogrel–aspirin therapy was associated with a marked reduction in new strokes compared with the therapy of aspirin alone in patients with normal renal function (hazard ratio, 0.77; 95% confidence interval, 0.60–0.98;
P
=0.02) and mild CKD (hazard ratio, 0.60; 95% confidence interval, 0.45–0.79;
P
<0.01), whereas in patients with moderate CKD, no significant benefit from clopidogrel therapy was detected (hazard ratio, 1.00; 95% confidence interval, 0.43–2.35;
P
=0.99). There was no clear difference in bleeding episodes by treatment assignment across categories of renal impairment.

Conclusions—
Clopidogrel plus aspirin could decrease new stroke in patients with normal kidney function and mild CKD, but no extra benefit was observed in those with moderate CKD. Bleeding risk from the dual therapy did not seem to increase in mild or moderate CKD patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00979589.
Evaluation of sodium tetradecyl sulfate and polidocanol as sclerosants for leg telangiectasia based on histological evaluation with clinical correlation
Authors: Bush Ronald , Bush Peggy 
Published: October 2016

Introduction This study was designed to determine by histological evaluation and clinical correlation the most effective sclerosant concentration of Sotradecol® (sodium tetradecyl sulfate) and Asclera® (polidocanol) for the treatment of leg telangiectasia. Methods Histological studies were completed on 40 patients, all of whom were female with a mean age of 53. After sclerotherapy with varying concentrations of sclerosant solutions for the treatment of 0.8 mm and 1 mm leg telangiectasia, histological specimens were examined for the following criteria: luminal changes, subintimal changes, smooth muscle wall alterations, and vessel wall integrity. Six patients from this group were also treated with sodium tetradecyl sulfate foam 0.1%–0.2% or polidocanol foam 0.31% for the treatment of 2 mm reticular veins. In a second group of 20 patients, clinical results after treatment with sodium tetradecyl sulfate 0.15% and polidocanol 0.31% were evaluated. Results Histological findings in patients treated with sodium tetradecyl sulfate 0.05% and polidocanol 0.25% were minimal. Sclerosant concentrations of sodium tetradecyl sulfate ≥0.2% revealed intraluminal debris and greater smooth wall damage. Polidocanol 0.5% was equivalent in strength to sodium tetradecyl sulfate 0.2% on histological evaluation. Sodium tetradecyl sulfate 0.15% and polidocanol 0.31% had similar findings on histological examination with mild smooth muscle wall changes, endothelial cell lysis, and subintimal layer damage. Reticular veins treated with 0.1%, 0.15%, and 0.2% sodium tetradecyl sulfate foam and 0.31% polidocanol foam produced identical histological findings. Conclusion Sodium tetradecyl sulfate 0.15% and polidocanol 0.31% based on histological evaluations and clinical correlation are the best sclerosant concentrations for 0.8 mm to 1 mm leg telangiectasia. Sodium tetradecyl sulfate foam is comparable to polidocanol foam at these concentrations as well.
YouTube as a potential source of information on deep venous thrombosis
Authors: Bademci Mehmet Ş , Yazman Serkan , Güneş Tevfik , Ocakoglu Gokhan , Tayfur Kaptanderya , Gokalp Orhan 
Published: October 2016

Background No work has been reported on the use of video websites to learn about deep vein thrombosis and the value of education using them. We examined the characteristics and scientific accuracy of videos related to deep vein thrombosis on YouTube. Methods YouTube was surveyed using no filter and the key words ‘deep vein thrombosis’ and ‘leg vein clot’ in June 2016. The videos evaluated were divided into three groups in terms of their scientific content, accuracy, and currency: useful, partly useful, and useless. Results Of the 1200 videos watched, 715 (59.58%) were excluded with the exclusion criteria. Although most of the videos uploaded (22.9%, n = 111) were created by physicians, the number of views for website-based videos was significantly higher (p = 0.002). When the uploaded videos were assessed in terms of their usefulness, videos from physicians and hospitals were statistically more useful than other videos (p < 0.001). Conclusions For videos created by medical professionals to be of higher quality, we believe they should be more up-to-date and comprehensive, and contain animations about treatment modalities and early diagnosis in particular.
Factors Associated with Timely Physician Follow-up after a First Diagnosis of Psychotic Disorder
Authors: Anderson Kelly K. , Kurdyak Paul 
Published: October 2016

Objective: Physician follow-up after a first diagnosis of psychotic disorder is crucial for improving treatment engagement. We examined the factors associated with physician follow-up within 30 days of a first diagnosis of schizophrenia. Method: We conducted a retrospective cohort study using linked health administrative data to identify incident cases of schizophrenia between 1999 and 2008 among people aged 14 to 35 years in Ontario. We estimated the proportion of patients who had physician follow-up within 30 days of the index diagnosis. We used multilevel logistic regression models to examine the factors associated with any physician follow-up and follow-up by a psychiatrist. Results: We identified 20,096 people with a first diagnosis of schizophrenia. Approximately 40% of people did not receive any physician follow-up within 30 days, and nearly 60% did not receive follow-up by a psychiatrist. Males had lower odds of receiving any physician follow-up, and the odds of psychiatrist follow-up decreased with increasing age and were lower for those living in rural areas. Both prior contact with a general practitioner for a mental health reason and prior contact with a psychiatrist were strongly associated with higher odds of receiving both types of follow-up. Conclusions: Many people do not have any physician contact within 30 days of the first diagnosis of schizophrenia, and patients without prior engagement with mental health services are at highest risk. We need information on the reasons behind this lack of physician follow-up to inform strategies aimed at improving engagement with services during the early stages of psychosis.
Next-generation multiple myeloma treatment: a pharmacoeconomic perspective
Authors: Rajkumar S. Vincent , Harousseau Jean Luc 
Published: October 2016

Abstract
Advances in the diagnosis and treatment of multiple myeloma have come at a rapid pace, especially with several new drugs entering the market in the last few years. However, access to and affordability of new treatments poses a major challenge, both in the United States and around the world. High costs of life-saving drugs are detrimental to both the personal finances of the individual patient, as well as society which must bear the increasing costs in terms of increased health insurance premiums, taxes, or both. The challenges are not unique to myeloma, but are commonly encountered in several other cancers as well. But to some extent these pharmacoeconomic concerns are amplified in myeloma due to the need for multidrug regimens that combine 2 or more expensive new drugs, continuous therapy, and the prolonged disease course in most patients. We examine current myeloma therapy from a pharmacoeconomic perspective, and discuss the costs involved. We outline the underlying reasons why cancer drugs are so expensive, the measures that are required to lower cost, and propose potential ways in which costs can be reduced while still delivering high-quality care.
Imaging of Hemorrhagic Stroke
Authors: Hakimi Ryan , Garg Ankur 
Published: October 2016

ABSTRACT

Purpose of Review: Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes.

Recent Findings: The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient’s medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management. Given that hemorrhagic stroke constitutes a heterogeneous collection of diagnoses, the subsequent neuroimaging pathway necessary to better evaluate and care for these patients is variable based on the etiology.
With an increasing incidence and prevalence of atrial fibrillation associated with the aging population and the introduction of three new direct factor Xa inhibitors and one direct thrombin inhibitor to complement vitamin K antagonists, oral anticoagulant use continues to increase. Patients on oral anticoagulants have a sevenfold to tenfold increased risk for intracerebral hemorrhage (ICH). Furthermore, patients who have an ICH associated with oral anticoagulant use have a higher mortality rate than those with primary ICH. Despite the reduced incidence of hypertension-related ICH over the past decade, it is expected that the incidence of ICH will continue to increase.

Summary: Neuroimaging studies are integral to the identification of hemorrhagic stroke, determination of the underlying etiology, prevention of hematoma expansion, treatment of acute complications, and treatment of the underlying etiology, if indicated. Neuroimaging is essential for prognostication and thus directly impacts patient care.
Eyes shut homolog is required for maintaining the ciliary pocket and survival of photoreceptors in zebrafish
Authors: Yu Miao , Liu Yu , Li Jing , Natale Brianna N. , Cao Shuqin , Wang Dongliang , Amack Jeffrey D. , Hu Huaiyu 
Published: October 2016

ABSTRACT
Mutations in the extracellular matrix protein eyes shut homolog (EYS) cause photoreceptor degeneration in patients with retinitis pigmentosa 25 (RP25). Functions of EYS remain poorly understood, due in part to the lack of an EYS gene in mouse. We investigated the localization of vertebrate EYS proteins and engineered loss-of-function alleles in zebrafish. Immunostaining indicated that EYS localized near the connecting cilium/transition zone in photoreceptors. EYS also strongly localized to the cone outer segments and weakly to the rod outer segments and cone terminals in primate retinas. Analysis of mutant EYS zebrafish revealed disruption of the ciliary pocket in cone photoreceptors, indicating that EYS is required for maintaining the integrity of the ciliary pocket lumen. Mutant zebrafish exhibited progressive loss of cone and rod photoreceptors. Our results indicate that EYS protein localization is species-dependent and that EYS is required for maintaining ciliary pocket morphology and survival of photoreceptors in zebrafish.