bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term time trends in incidence, survival and mortality of lymphomas by subtype among adults in Manitoba, Canada: a population-based study using cancer registry data
Authors: Ye Xibiao , Mahmud Salaheddin , Skrabek Pamela , Lix Lisa , Johnston James B
Published: July 2017

Objective

To examine 30-year time trends in incidence, survival and mortality of lymphomas by subtype in Manitoba, Canada.

Methods

Lymphoma cases diagnosed between 1984 and 2013 were classified according to the 2008 WHO classification system for lymphoid neoplasms. Death data (1984–2014) were obtained from the Manitoba Vital Statistics Agency. To examine time trends in incidence and mortality, we used joinpoint regression to estimate annual percentage change and average annual percentage change. Age–period–cohort modelling was conducted to measure the effects of age, period and cohort on incidence and mortality time trends. We estimated age-specific and standardised 5-year relative survival and used Poisson regression model to test time trends in relative survival.

Results

Total Hodgkin lymphoma (HL) incidence in men and women was stable during the study period. Age-standardised total non-Hodgkin lymphoma (NHL) incidence increased by 4% annually until around 2000, and the trend varied by sex and NHL subtype. Total HL mortality continuously declined (by 2.5% annually in men and by 2.7% annually in women), while total NHL mortality increased (by 4.4% annually in men until 1998 and by 3.2% annually in women until 2001) and then declined (by 3.6% annually in men and by 2.5% annually in women). Age-standardised 5-year relative survival for HL improved from 72.6% in 1984–1993 to 85.8% in 2004–2013, and for NHL from 57.0% in 1984–1993 to 67.5% in 2004–2013. Survival improvement was also noted for NHL subtypes, although the extent varied, with the greatest improvement for follicular lymphoma (from 65.3% in 1984–1993 to 87.6% in 2004–2013).

Conclusions

Time trends were generally consistent with those reported in other jurisdictions in total HL and NHL incidence, but were unique in incidence for HL and for NHL subtypes chronic/small lymphocytic leukaemia/lymphoma, diffuse large B cell lymphoma and follicular lymphoma. Survival improvements and mortality reductions were seen for HL and NHL in both sexes.
Influence of family history on the willingness of outpatients to undergo genetic testing for salt-sensitive hypertension: a cross-sectional study
Authors: Takeshima Taro , Okayama Masanobu , Ae Ryusuke , Harada Masanori , Kajii Eiji
Published: July 2017

Objectives

It is unclear whether family medical history influences the willingness to undergo genetic testing. This study aimed to determine how family history affected the willingness to undergo genetic testing for salt-sensitive hypertension in patients with and without hypertension.

Design

Cross-sectional study using a self-administered questionnaire.

Setting

Six primary care clinics and hospitals in Japan.

Participants

Consecutive 1705 outpatients aged >20 years, 578 of whom had hypertension.

Primary and secondary outcome measures

The primary outcome variable was the willingness to undergo genetic testing to determine the risk of salt-sensitive hypertension, and the secondary variables were age, sex, education level, family history and concerns about hypertension. Factors associated with a willingness to undergo genetic testing were evaluated in patients with and without hypertension using a logistic regression model.

Results

In the hypertension and non-hypertension groups, 323 (55.9%) and 509 patients (45.2%), respectively, were willing to undergo genetic testing. This willingness was related with a high level of education (adjusted OR (ad-OR): 1.81, 95% CI 1.12 to 2.93), family history of stroke (1.55, 1.04 to 2.31) and concerns about hypertension (2.04, 1.27 to 3.28) in the hypertension group, whereas in the non-hypertension group, it was influenced by education level (ad-OR: 1.45, 95% CI 1.13 to 1.86), family history of hypertension (1.52, 1.17 to 1.98) and concerns about hypertension (2.03, 1.53 to 2.68).

Conclusions

The influence of family history on the willingness to undergo genetic testing for risk of salt-sensitivity hypertension differed between participants with and without hypertension. In particular, participants without hypertension wished to know their likelihood of developing hypertension, whereas those with hypertension were interested to know the risk of stroke (a complication of hypertension). Family history could help better counsel patients about genetic testing on the basis of their medical history.
Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial)
Authors: Hopewell Sally , Keene David J , Maia Schlüssel Michael , Dritsaki Melina , Dutton Susan , Carr Andrew , Hamilton William , Hansen Zara , Jaggi Anju , Littlewood Chris , Soutakbar Hessam , Heine Peter , Cureton Lucy , Barker Karen , Lamb Sarah E
Published: July 2017

Introduction

Shoulder pain is very common, with around 70% of cases due to disorders of the rotator cuff. Despite widespread provision of physiotherapy, there is uncertainty about which type of exercise and delivery mechanisms are associated with best outcomes. There is also uncertainty around the long-term benefits and harms of corticosteroid injection therapy, which is often used in addition to physiotherapy. The Getting it Right: Addressing Shoulder Pain trial will assess the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder.

Methods and analysis

We are conducting a large multicentre randomised controlled trial (2×2 factorial design). We will recruit adults ≥18 years with a new episode of shoulder pain attributable to a rotator cuff disorder as per British Elbow and Shoulder Society guidelines, not currently receiving physiotherapy or being considered for surgery, from at least eight UK National Health Service primary care-based musculoskeletal and related physiotherapy services. Participants (n=704) will be randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (≤6 physiotherapy sessions); (2) best practice advice (one physiotherapy session); (3) corticosteroid injection then progressive exercise (≤6 sessions) or (4) corticosteroid injection then best practice advice (one session). The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score at 12 months. Secondary outcomes are: pain and function SPADI subdomains; health-related quality of life (Five-Level version of the EuroQol EQ-5D-5L); sleep disturbance; return to activity; global impression of change; health resource use; out-of-pocket expenses; work disability. A parallel within-trial economic evaluation will be conducted. The primary analysis will be intention to treat.

Ethics and dissemination

Research Ethics Committee approval (REC: 16/SC/0508) has been obtained. Results of the main trial and secondary outcomes will be submitted for publication in a peer-reviewed journal.

Trial registration number

ISRCTN16539266; EudraCT number: 2016-002991-28.
Diagnostic challenges and surgical treatment of hydroureteronephrosis in a rabbit (Oryctolagus cuniculus)
Authors: Tahas Stamatios Alan , Pope Juliet , Denk Daniela , Saunders Richard
Published: July 2017

A two‐and‐half‐year‐old male neutered rabbit was referred for investigation of intermittent urinary disease of 13 months in duration. Case work‐up led to the diagnosis of unilateral hydroureteronephrosis following obstructive ureterolithiasis. The establishment of contralateral kidney function before ureteronephrectomy constituted a particular diagnostic challenge. This was assessed by a combination of imaging, serum biochemistry, urine protein to creatinine ratio and γ‐glutamyltransferase index. Ureteronephrectomy was subsequently performed, with initial remission of all clinical signs. However, an adhesion of mesenteric adipose tissue to the caecum was identified and resected following frequent re‐presentation. At the time of submission (800 days following initial surgery), the rabbit was still alive and healthy. The successful outcome may indicate a more favourable prognosis for rabbits with unilateral ureteronephrolithiasis and/or hydroureteronephrosis than is historically proposed.
Feline progressive dendritic cell histiocytosis in a domestic long hair feline
Authors: Solc Meghan , Jazic Edward , Crandell John , Loeffler Diana
Published: July 2017

A six‐year‐old male castrated domestic long hair feline presented for evaluation of a progressive cutaneous nodular dermatosis and an acute onset of dyspnoea. The patient had an initial skin biopsy performed with a tentative diagnosis of mycobacteriosis; however, acid‐fast stains were negative. Thoracic radiographs revealed multifocal, large pulmonary nodules. Aerobic bacterial, fungal and mycobacterial cultures, as well as Histoplasma and Cryptococcus antigen tests, were all negative. Re‐evaluation of the biopsy provided a diagnosis of feline progressive dendritic cell histiocytosis. The samples revealed a focally marked to diffuse coalescing superficial to deep perivascular and periadnexal infiltrates of numerous moderately large histiocytic cells. Unfortunately, there is no successful treatment for this disease and the patient was humanely euthanased.
Exploration of the 150 cavity and the role of serendipity in the discovery of inhibitors of influenza virus A neuraminidase
Authors: Mohan Sankar , Pinto B. Mario
Published: July 2017

Influenza pandemics are an ongoing threat for the human population, as the avian influenza viruses H5N1 and H7N9 continue to circulate in the bird population and the chance of avian to human transmission increases. Neuraminidase, a glycoprotein located on the surface of the influenza virus, plays a crucial role in the viral replication process and, hence, has proven to be a useful target enzyme for the treatment of influenza infections. The discovery that certain subtypes of influenza neuraminidase have an additional cavity, the 150 cavity, near the substrate binding site has triggered considerable interest in the design of influenza inhibitors that exploit this feature. Currently available antiviral drugs, neuraminidase inhibitors oseltamivir and zanamivir, were designed using crystal structures predating this discovery by some years. This mini review is aimed at summarizing our group’s efforts, together with related work from other groups, on neuraminidase inhibitors that are designed to exploit both the catalytic site and the 150 cavity. The design of a parent scaffold that yields a potent inhibitor that is active in cell culture assays and retains activity against several neuraminidases from mutant strains is also described. Finally, the role of serendipity in the discovery of a new class of potent neuraminidase inhibitors with a novel spirolactam scaffold is also highlighted.
Data needs and spatial structure considerations in stock assessments with regional differences in recruitment and exploitation
Authors: Denson LaTreese S. , Sampson David B. , Stephens Andi
Published: July 2017

This study uses a simulation experiment to demonstrate that bias in estimates of spawning biomass is influenced by the spatial configuration of a stock assessment model, whether survey data are used or not and whether an environmental index is available to inform the spatial distribution of recruitment. Stocks with limited movement of postsettlement fish may be spatially structured due to environmental forces that affect larval dispersal and recruitment distribution or from nonuniform spatial exploitation. Data are frequently aggregated across space in stock assessments, thus disregarding this complex spatial structure and possibly introducing bias into estimates of stock status. An operating model (OM) is created that simulates data that are used in a set of estimation models to assess bias. The following experimental factors are considered: (i) using survey data and environmental indices in the assessment; (ii) using disaggregated data (two regions, as generated by the OM) or aggregated data (one region); and (iii) incorporating different patterns in the OM’s regional exploitation and environmentally driven recruitment distribution.
Quantifying downed coarse woody material and residual forest basal area following retention harvesting in northeastern Minnesota using Landsat sensor data
Authors: Wolter P.T. , Hilgemann L.A. , White M.A.
Published: July 2017

Retention harvesting shows great promise for restoring and maintaining forest structural and compositional diversity. However, economical, comprehensive monitoring is needed to advance understanding of the effectiveness of these management strategies through time. We investigate multitemporal winter Landsat sensor data (capturing snow ground cover at 7.6 cm and 106.7 cm depths) as a tool for discriminating between and providing regional estimates of both residual forest basal area (BA) and downed coarse woody material (DCWM) volume following retention harvesting in Minnesota, USA. Measurements from 34 ground plots were used with Landsat predictor variables to estimate these two biophysical forest parameters. According to similar studies, results for DCWM volume estimation are considered adequate, with an R2adj = 0.54 and absolute RMSE (RMSEa) = 19.02 m3·ha−1. Residual forest BA estimates were similar: total BA R2adj = 0.55 (RMSEa = 1.85 m2·ha−1), hardwood BA R2adj = 0.67 (RMSEa = 1.23 m2·ha−1), and conifer BA R2adj = 0.52 (RMSEa = 0.94 m2·ha−1). Use of winter Landsat imagery was key to quantifying these important forest biophysical parameters — a tool that carries the potential to transform our understanding of the impact of human and natural disturbance regimes on northern forest ecosystems.
Marriage and Migration
Authors: Brettell Caroline B.
Published: July 2017

Despite immigration policies that are often built around family reunification, contemporary research on migration often prioritizes labor mobility over mobility associated with marriage and family formation. Drawing on scholarship across a range of disciplines and across the globe, this article focuses attention on the substantive dimensions and theoretical debates located at the intersections of research on marriage and migration. Among the topics covered are rural bride shortages and mail-order marriages, arranged marriages, marriages of convenience and the state policies introduced to regulate them, and crimes of honor. The article also addresses the impact of migration on spousal relationships and on parenting in a transnational context. Of particular consideration are dimensions of insecurity that arise in mixed-status families, which may result in domestic violence.
The Role of Efflux Pumps in Tuberculosis Treatment and Their Promise as a Target in Drug Development: Unraveling the Black Box
Authors: te Brake Lindsey H.M. , de Knegt Gerjo J. , de Steenwinkel Jurriaan E. , van Dam Teunis J.P. , Burger David M. , Russel Frans G.M. , van Crevel Reinout , Koenderink Jan B. , Aarnoutse Rob E.
Published: July 2017

Insight into drug transport mechanisms is highly relevant to the efficacious treatment of tuberculosis (TB). Major problems in TB treatment are related to the transport of antituberculosis (anti-TB) drugs across human and mycobacterial membranes, affecting the concentrations of these drugs systemically and locally. Firstly, transporters located in the intestines, liver, and kidneys all determine the pharmacokinetics and pharmacodynamics of anti-TB drugs, with a high risk of drug-drug interactions in the setting of concurrent use of antimycobacterial, antiretroviral, and antidiabetic agents. Secondly, human efflux transporters limit the penetration of anti-TB drugs into the brain and cerebrospinal fluid, which is especially important in the treatment of TB meningitis. Finally, efflux transporters located in the macrophage and Mycobacterium tuberculosis cell membranes play a pivotal role in the emergence of phenotypic tolerance and drug resistance, respectively. We review the role of efflux transporters in TB drug disposition and evaluate the promise of efflux pump inhibition from a novel holistic perspective.
Economics of US State and Local Regulation of Farm Practices, with Emphasis on Restrictions of Interstate Trade
Authors: Sumner Daniel A.
Published: July 2017

This review focuses on the economics of policies in US states (or localities) that have regulated farm practices and related behavior. Some of these policies represent long-standing policies to govern the nature of farm organization, such as regulation of corporate ownership, investment, or organization. Other more recent policies attempt to affect specific scientific innovations, such as the use of seeds developed using modern biology (e.g., foods from genetically modified organisms). Another recent group of state laws and regulations addresses treatment of farm animals. Finally, treatment of the production and marketing of marijuana is the most recent state agricultural regulation to spark widespread interest and controversy. State and local regulations of farm practices are of broad practical interest because they affect markets beyond their jurisdictions. Broad concerns also follow if the regulations set legal or political precedents, or when rules apply to farm practices in outside jurisdictions.
Astrovirus Biology and Pathogenesis
Authors: Cortez Valerie , Meliopoulos Victoria A. , Karlsson Erik A. , Hargest Virginia , Johnson Cydney , Schultz-Cherry Stacey
Published: July 2017

Astroviruses are nonenveloped, positive-sense single-stranded RNA viruses that cause gastrointestinal illness. Although a leading cause of pediatric diarrhea, human astroviruses are among the least characterized enteric RNA viruses. However, by using in vitro methods and animal models to characterize virus-host interactions, researchers have discovered several important properties of astroviruses, including the ability of the astrovirus capsid to act as an enterotoxin, disrupting the gut epithelial barrier. Improved animal models are needed to study this phenomenon, along with the pathogenesis of astroviruses, particularly in those strains that can cause extraintestinal disease. Much like for other enteric viruses, the current dogma states that astroviruses infect in a species-specific manner; however, this assumption is being challenged by growing evidence that these viruses have potential to cross species barriers. This review summarizes these remarkable facets of astrovirus biology, highlighting critical steps toward increasing our understanding of this unique enteric pathogen.
Low Dose of Lipopolysaccharide Pretreatment Preventing Subsequent Endotoxin-Induced Uveitis Is Associated with PI3K/AKT Pathway
Authors: Zhang Nan , Yu Shuo , Liu Xinli , Lu Hong
Published: July 2017

Purpose. To explore the effects of LPS pretreatment on endotoxin-induced uveitis and PI3K/AKT pathway. Methods. Endotoxin-induced uveitis was induced by a single subcutaneous injection of 200 μg LPS. For the endotoxin tolerance group, induction of EIU was preceded by daily subcutaneous injection of 0.1 mg/kg LPS for five days. Clinical scores were graded at 24 h after EIU under a slit lamp microscope. HE stain was performed to observe the histopathology. Aqueous humor TNF-α concentration was quantified with enzyme-linked immunosorbent assay. The expressions of PI3K and AKT were detected through Western blot analyses, and the activation of AKT was detected through immunofluorescence study. Results. Endotoxin tolerance produced suppressive effects by significantly reducing the inflammatory reaction of anterior segment of the rats as measured by slit lamp and histopathology. Low dose of LPS pretreatment significantly reduced TNF-α concentrations and the expressions of PI3K and AKT. Furthermore, the activation of AKT was also inhibited. Conclusions. LPS pretreatment can ameliorate endotoxin-induced uveitis in rats. This protection of endotoxin tolerance against EIU is associated with PI3K/AKT pathway by reducing level of TNF-α in the aqueous humor.
Trends and Disparities in the Prevalence of Childhood Obesity in South Texas between 2009 and 2015
Authors: Foster Byron A. , Maness Trevor M. , Aquino Christian A.
Published: July 2017

Background. Recent reports have highlighted possible decreases over time in obesity, particularly among children aged 2–5 years. Hispanic children experience significantly higher obesity rates, and less is known about trends for Hispanic children.Methods. A large healthcare system-based dataset from south Texas was used to analyze body mass index (BMI) values obtained clinically from 2009 through 2015. Age and race/ethnicity specific prevalence of overweight and obesity were calculated using CDC standards and trends were examined over time using regression analyses, and mapping software was used to identify geographic variation.Results. Hispanic children in south Texas experience levels of obesity (25.3%, 95% CI: 25.1–25.6) significantly higher than their white (16.6%, 95% CI: 16.0–17.2) or black (18.2%, 95% CI: 17.3–19.1) peers. Obesity in Hispanic children aged 2–5 years decreased from 18.5%, 95% CI: 16.6–20.5, in 2009 to 15.1%, 95% CI: 14.3–15.9, in 2015. Obesity in Hispanic adolescents was stable at 30.4%, 95% CI: 28.5–32.4, in 2009 and 31.3, 95% CI: 30.3–32.2, in 2015.Conclusions. While obesity decreased in the youngest age group of Hispanic children, south Texas continues to experience high levels of obesity that exceed national averages with significant disparities.
Improved k-t PCA Algorithm Using Artificial Sparsity in Dynamic MRI
Authors: Wang Yiran , Chen Zhifeng , Wang Jing , Yuan Lixia , Xia Ling , Liu Feng
Published: July 2017

The k-t principal component analysis (k-t PCA) is an effective approach for high spatiotemporal resolution dynamic magnetic resonance (MR) imaging. However, it suffers from larger residual aliasing artifacts and noise amplification when the reduction factor goes higher. To further enhance the performance of this technique, we propose a new method called sparse k-t PCA that combines the k-t PCA algorithm with an artificial sparsity constraint. It is a self-calibrated procedure that is based on the traditional k-t PCA method by further eliminating the reconstruction error derived from complex subtraction of the sampled k-t space from the original reconstructed k-t space. The proposed method is tested through both simulations and in vivo datasets with different reduction factors. Compared to the standard k-t PCA algorithm, the sparse k-t PCA can improve the normalized root-mean-square error performance and the accuracy of temporal resolution. It is thus useful for rapid dynamic MR imaging.
Large Granular Lymphocytic Leukemia: A Report of Response to Rituximab
Authors: Ibrahim Uroosa , Parylo Sara , Kedia Shiksha , Hussein Shafinaz , Atallah Jean Paul
Published: July 2017

Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months’ duration. A CBC showed that pancytopenia with an absolute neutrophil count (ANC) was 0. Peripheral blood flow cytometry detected increased number of T cell large granular lymphocytes and T cell receptor rearrangement study detected a clonal T cell population. Bone marrow biopsy showed peripheral T cell lymphoma, most consistent with T-large granulocytic leukemia. The patient was treated with prednisone and oral cyclophosphamide for four months with no response. Thereafter, she received four weekly infusions of rituximab with improvement in her blood counts. A response to rituximab in refractory cases such as ours has been reported and may guide us towards exploring other immune-based therapeutics in this rare disease.
Out‐of‐Plane Vibration of Curved Uniform and Tapered Beams with Additional Mass
Authors: Özyiğit Hamdi Alper , Yetmez Mehmet , Uzun Utku
Published: July 2017

As there is a gap in literature about out‐of‐plane vibrations of curved and variable cross‐sectioned beams, the aim of this study is to analyze the free out‐of‐plane vibrations of curved beams which are symmetrically and nonsymmetrically tapered. Out‐of‐plane free vibration of curved uniform and tapered beams with additional mass is also investigated. Finite element method is used for all analyses. Curvature type is assumed to be circular. For the different boundary conditions, natural frequencies of both symmetrical and unsymmetrical tapered beams are given together with that of uniform tapered beam. Bending, torsional, and rotary inertia effects are considered with respect to no‐shear effect. Variations of natural frequencies with additional mass and the mass location are examined. Results are given in tabular form. It is concluded that (i) for the uniform tapered beam there is a good agreement between the results of this study and that of literature and (ii) for the symmetrical curved tapered beam there is also a good agreement between the results of this study and that of a finite element model by using MSC.Marc. Results of out‐of‐plane free vibration of symmetrically tapered beams for specified boundary conditions are addressed.
Subjective Global Assessment and Handgrip Strength as Predictive Factors in Patients with Liver Cirrhosis
Authors: Ciocîrlan Maria , Cazan Andreea Ruxandra , Barbu Mihaela , Mănuc Mircea , Diculescu Mircea , Ciocîrlan Mihai
Published: July 2017

Background and Aims. Malnutrition is common in patients with chronic liver disease. We aimed to evaluate malnutrition assessment tools in predicting severity and survival of patients with liver cirrhosis. Material and Methods. We examined patients with liver cirrhosis. Nutritional evaluation was performed on admission, using subjective global assessment (SGA), handgrip strength (HGS), and anthropometry. Patients were followed up for 6 months. Results. We included 100 patients, 72 men, with mean age of 59.2 years. According to disease severity, patients were 23% Child-Pugh A, 46% Child-Pugh B, and 31% Child-Pugh C. SGA and HGS significantly correlated with Child-Pugh, MELD, and MELD-Na scores on admission. At 6 months follow-up, 80.4% (78 of 97) of patients survived, while 3 patients were lost from observation. Survival was predicted by SGA (1 death in 32 patients SGA A, 8 deaths in 46 patients SGA B, and 9 deaths in 19 patients SGA C, p=0.001) and HGS (25.1 ± 8.5 in deceased versus 30.6 ± 10.9 in survivors, p=0.046). The mean BMI and MAMC values did not significantly differ between patients who survived or were deceased at 6 months. Conclusion. HGS and SGA may predict severity and short-term survival in cirrhotic patients.
Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate
Authors: Iqbal Mohamed Ariff , Eftekharpour Eftekhar
Published: July 2017

In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS) reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS) in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.
Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers
Authors: Murlidhar Vasudha , Reddy Rishindra M. , Fouladdel Shamileh , Zhao Lili , Ishikawa Martin K. , Grabauskiene Svetlana , Zhang Zhuo , Lin Jules , Chang Andrew C. , Carrott Philip , Lynch William R. , Orringer Mark B. , Kumar-Sinha Chandan , Palanisamy Nallasivam , Beer David G. , Wicha Max S. , Ramnath Nithya , Azizi Ebrahim , Nagrath Sunitha
Published: July 2017

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe (P < 0.0001) and intraoperative Pe (P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194–206. ©2017 AACR.
Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth
Authors: Spyrou Argyris , Kundu Soumi , Haseeb Lulu , Yu Di , Olofsson Tommie , Dredge Keith , Hammond Edward , Barash Uri , Vlodavsky Israel , Forsberg-Nilsson Karin
Published: July 2017

Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM. Here, we report that the levels of HPSE in pediatric brain tumors are higher than in healthy brain tissue and that treatment of pediatric brain tumor cells with HPSE stimulated their growth. In addition, the latent, 65 kDa form of HPSE (that requires intracellular enzymatic processing for activation) enhanced cell viability and rapidly activated the ERK and AKT signaling pathways, before enzymatically active HPSE was detected. The HPSE inhibitor PG545 efficiently killed pediatric brain tumor cells, but not normal human astrocytes, and this compound also reduced tumor cell invasion in vitro and potently reduced the size of flank tumors in vivo. Our findings indicate that HPSE in malignant brain tumors affects both the tumor cells themselves and their ECM. In conclusion, HPSE plays a substantial role in childhood brain tumors, by contributing to tumor aggressiveness and thereby represents a potential therapeutic target. Mol Cancer Ther; 16(8); 1705–16. ©2017 AACR.
Potency-matched Dual Cytokine–Antibody Fusion Proteins for Cancer Therapy
Authors: De Luca Roberto , Soltermann Alex , Pretto Francesca , Pemberton-Ross Catherine , Pellegrini Giovanni , Wulhfard Sarah , Neri Dario
Published: July 2017

A novel biopharmaceutical, consisting of the F8 mAb (specific to a splice isoform of fibronectin) simultaneously fused to both TNF and IL2, was found to react with the majority of solid tumors and hematologic malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNFmut) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody–cytokine fusion proteins or by standard doxorubicin treatment. Durable complete responses were also observed in mice bearing CT26, C1498, and F9 tumors. The simultaneous delivery of multiple proinflammatory payloads to the cancer site conferred protective immunity against subsequent tumor challenges. A fully human homolog of IL2-F8-TNFmut, which retained selectivity similar to its murine counterpart when tested on human material, may open new clinical applications for the immunotherapy of cancer. Mol Cancer Ther; 16(11); 2442–51. ©2017 AACR.
Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder
Authors: Crider Amanda , Ahmed Anthony O. , Pillai Anilkumar
Published: July 2017

The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible synaptic genes induce ER stress. However, it is not known whether ER stress-related genes are altered in the brain of ASD subjects. In the present study, we investigated the mRNA expression of ER stress-related genes (ATF4, ATF6, PERK, XBP1, sXBP1, CHOP, and IRE1) in the postmortem middle frontal gyrus of ASD and control subjects. RT-PCR analysis showed significant increases in the mRNA levels of ATF4, ATF6, PERK, XBP1, CHOP, and IRE1 in the middle frontal gyrus of ASD subjects. In addition, we found a significant positive association of mRNA levels of ER stress genes with the diagnostic score for stereotyped behavior in ASD subjects. These results, for the first time, provide the evidence of the dysregulation of ER stress genes in the brain of subjects with ASD.
Синдром ендогенної інтоксикації в щурів із гострим поширеним перитонітом на тлі мерказоліл-індукованого гіпотиреозу
Authors: Verba R. I. , Klishch I. M.
Published: July 2017

Introduction. The growth of endogenous toxicosis occurs when the admission intensity of toxic metabolic products increased sharply, or when the activity of antitoxic systems or elimination of toxic metabolites inhibits. The syndrome of endogenous intoxication develops at various pathological conditions, when the number of natural waste products of the body, which appeared in large quantities in biological environments, as well as aggressive components exceeds the capacity of biotransformation. The aim of the study – to learn the effect of reduced production of thyroid hormones on the indices of endogenous intoxication of rats with acute widespread peritonitis.Research Methods. The study used white Wistar rats. Hypothyroidism was simulated by the administration of Mercazolil at a dose of 25 mg / kg for 21 days. Acute widespread peritonitis was simulated by injecting 0.5 ml of 10 % filtered fecal suspension into the abdominal cavity of the studied animals. The determination of molecules of average weight, erythrocyte and leukocyte indices of intoxication, level of circulating immune complexes and catepsin D was carried out.Results and Discussion. It was established that the presence of hypothyroidism in experimental animals to which was simulated acute widespread faecal peritonitis was accompanied by, more expressed than in euthyroid rats, increase in endotoxicosis – medium molecular weight peptides, erythrocyte and leukocyte indices of intoxication, circulating immune complexes and worse dynamics of their normalization. Phase changes in cathepsin D activity were observed.Conclusions. Deficiency of iodine-containing thyroid hormones is accompanied by a reliable increase in the indices characterizing the syndrome of endogenous intoxication in comparison with the euthyroid animals. This may be one of the reasons for the development of multiple organ failure in these conditions.
The Canonical Order of Russian Objects
Authors: Titov Elena
Published: July 2017

According to the principles of economy, scrambled orders require an interpretive license. Removal of such a license should result in canonical orders, that is, orders I hypothesize to be determined by a thematic hierarchy. It is traditionally assumed that the interpretive license for scrambling is provided by information-structural interpretations such as focus and background. However, either direct object–indirect object or indirect object–direct object order is possible in Russian all-focus constructions, complicating the choice of order analyzed as canonical. I argue that Russian scrambling can be licensed by a variety of interpretations, focus/background encoding being but one of them. When the construal of objects is neutralized on the basis of all of the relevant interpretations, the direct object–indirect object order surfaces, strongly suggesting that this is the canonical order of Russian objects.
The Future of the International Criminal Court. On Critique, Legalism and Strengthening the icc’s Legitimacy
Authors: de Hoon Marieke
Published: July 2017

While the International Criminal Court (icc) strives for justice for atrocity crimes throughout the world, increasingly, its legitimacy is undermined: powerful states refuse to join, African states prepare to leave, victims do not feel their needs for justice are met. This article argues that this is due to contradicting assumptions and too many objectives attached to the expectations of international criminal justice, which pull and push what the criminal trial is supposed to do in too many directions, undermining what it can do, raising too high expectations, and leading to disappointment. The article analyses the critique as rooted in a misunderstanding of what ‘justice’ is, what a criminal trial can do, and how inherently political international criminal justice is and only can be. It concludes with some observations on what this entails for strengthening the legitimacy of the icc by matching expectations to what it can and cannot do.
Muḥyī l-Dīn Ibn ʿArabī’s Personalist Theory of the Sharīʿa
Authors: Edaibat Omar
Published: July 2017

While Ibn ʿArabī (d. 638/1240) continues to receive much attention within the academe as a preeminent Sufi philosopher, his jurisprudence, by contrast, rarely elicits the same attention, despite the prominent mention of the Sharīʿa throughout his many works. This paper provides an exhaustive overview of his sophisticated legal doctrine in terms of his legal methodology and substantive law. An analysis of his legal epistemology would situate him within the ‘scripturalist’ stream of legal theorists, commonly associated with the Zāhiri school. However, while Ibn Ḥazm (d. 456/1064) certainly influenced Ibn ʿArabī’s legal doctrine, the Shaykh’s jurisprudence remains markedly original in that it is ultimately rooted in an overarching metaphysical doctrine. This is evident in his personal reframing of ijtihād as a personal process of spiritual refinement, as opposed to a methodical process of ratiocination, which leads him to develop a distinctively personalist theory of legal pluralism that transcends the limitations of school conformity.
Impatiens pseudolaevigata sp. nov. (Balsaminaceae): a new species from Western Arunachal Pradesh, India
Authors: GOGOI RAJIB , THAM B.B.T. , LIDÉN MAGNUS , BORAH SOURAVJYOTI
Published: July 2017

Impatiens pseudolaevigata from West Kameng district, Arunachal Pradesh, Northeast India, is newly described and illustrated. A detailed description, information on distribution and ecology, and colour photographs are provided for identification of the species.
On the typification and nomenclature of Rhododendron ×intermedium (Ericaceae)
Authors: SOSNOVSKY YEVHEN , NACHYCHKO VIKTOR , MRÁZ PATRIK
Published: July 2017

We discuss the typification and nomenclature of the name Rhododendron ×intermedium (Ericaceae). As the name R. ×intermedium Wenderoth is invalid, the earliest legitimate name for R. ferrugineum × R. hirsutum hybrid is the name published by Tausch. We designate one collection from PRC as the lectotype and two other specimens from PRC are considered to be a part of the original material. A list of R. ×intermedium synonyms is provided and two specimens from IBF are designated as the neotypes of two heterotypic synonyms, namely R. ×halense and R. ×hirsutiformum.
Aspidistra viridiflora (Asparagaceae, Nolinoideae), a new species from Vietnam
Authors: VISLOBOKOV NIKOLAY A. , KUZNETSOV ANDREY N. , KUZNETSOVA SVETLANA P. , ROMANOV MIKHAIL S. , NURALIEV MAXIM S.
Published: July 2017

One following the news of systematics of the genus Aspidistra Ker Gawler (1822: 628) should notice that the year 2016 brought us at least 16 new taxa, including 15 new species and one subspecies (Averyanov & Tillich 2016, Averyanov et al. 2016, Liang et al. 2016, Liu et al. 2016, Ly & Tillich 2016, Pan et al. 2016, Tanaka 2016, Vislobokov 2016, Vislobokov et al. 2016a, 2016b, Zhou et al. 2016). Indeed, Aspidistra is a large and rapidly growing genus which comprises about 160 species, including more than 60 of them known in Vietnam (e.g., Tillich 2005, 2008, 2014, Averyanov & Tillich 2015, 2017, Colin 2015, Vislobokov 2015, 2016, Averyanov et al. 2016, Vislobokov et al. 2016a, 2016b).
Polystichum luteoviride (subg. Haplopolystichum; Dryopteridaceae), a new, highly endangered cave species from Guizhou, China
Authors: DUAN YI-FANN , LU NGAN THI , ZHANG LIANG , ZHANG LI-BING
Published: July 2017

One new fern species, Polystichum luteoviride, a member of P. subg. Haplopolystichum (Dryopteridaceae), is described and illustrated from Guizhou Province in Southwest China. Polystichum luteoviride is similar to P. deflexum Ching ex W.M.Chu (1992: 47) in having crenate pinna margins, but the former has lamina yellowish green and pinnae oblong, strongly reflexed, and acute to obtuse at apex, while the latter has laminae green and pinnae lanceolate, slightly reflexed or even angled acroscopically, and acuminate at apex. Polystichum luteoviride was found inside a karst cave at an elevation of 1200 m with humid and shady conditions and is currently known from one population in Ziyun County, southern Guizhou, and is classified as Critically Endangered (CR) following IUCN Red List criteria.
Archaeochionelasmus nekvasilovae gen. et sp. nov. (Cirripedia, Balanomorpha, Chionelasmatoidea) from the Bohemian Cretaceous Basin (Czech Republic): the first bona fide Cretaceous neobalanoform
Authors: KOČÍ TOMÁŠ , VESELSKÁ MARTINA KOČOVÁ , NEWMAN WILLIAM A. , BUCKERIDGE JOHN S. , SKLENÁŘ JAN
Published: July 2017

This paper records a new sessile cirripede from a nearshore, shallow-water facies at Předboj near Prague, Czech Republic. The new taxon, Archaeochionelasmus nekvasilovae gen. et sp. nov., is the earliest known neobalanoform barnacle, and while it may have been an obligate commensal of a cephalopod or marine reptile, that it was a shore barnacle cannot be ruled out. (Zoobank registration: urn:lsid:zoobank.org:pub:177CC951-CEC1-425C-B693-46ADB83BD5D9)
A new species of Nuuanu (Crustacea, Amphipoda, Nuuanuidae) from a Caribbean coral reef with identification keys to males and females of Nuuanu species
Authors: ORTIZ MANUEL , WINFIELD IGNACIO
Published: July 2017

A new species of amphipod of the genus Nuuanu is described and illustrated, and is diagnosed against the morphologically most similar species. It was collected in coral rubble from a tropical coral reef, NW Caribbean Sea. The new species increases the number of Nuuanu species recorded to 20 worldwide. Nuuanu jaumei sp. nov., can be distinguished from other members of the genus by a combination of characters: head with bigeminal dispersed eyes; mammiliform lateral cephalic lobe; anteroventral notch of head well defined; antenna 1 geniculate; accessory flagellum 3–articulate; coxa 5 devoid of seta on ventromedial margin; article 2 anteroventral corner of pereopod 5 with a strong setae; epimera 1, 2, 3 with 2, 4, 1 ventral robust setae respectively; telson longer than broad; female gnathopod 2 with 2 long and slender setae on posterior margin. In addition, a key for the identification of all known male species of the genus Nuuanu, and another for the identification of the females, are also presented.
1. Love and Authority: Love Poetry and its Critics
Authors: Bryson Michael , Movsesian Arpi
Published: July 2017

The introduction establishes the overall concerns of the book, arguing that love, as treated in literature, has often been cast as a resistant force, a disobedience in the face of cultural figures and forces that demand obedience. The arguments for and against obedience as the prime virtue of a human life are outlined—ranging from Augustine, Aquinas, Luther, and Calvin, to Étienne de La Boétie, Jean-Jacques Rousseau, and John Milton. Finally, the kind of literary criticism that relies on the notion of unveiling what is hidden is outlined through a discussion of Ricoeur and Heidegger, and that criticism is tied back to the cultural figures and forces that demand obedience by way of suggesting the historical relation such criticism has to love as portrayed in poetry, beginning as early as the Song of Songs.