bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells
Authors: Liu Chun-Chun , Zhang Yun-Na , Li Zhao-Yao , Hou Jin-Xiu , Zhou Jing , Kan Lin , Zhou Bin , Chen Pu-Yan 
Published: July 2017

ABSTRACT
During infection Japanese encephalitis virus (JEV) generally enters host cells via receptor-mediated clathrin-dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and postinternalization of JEV were analyzed using biochemical inhibitors, RNA interference, and dominant negative (DN) mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol but not on caveolae or macropinocytosis. The effect on JEV infection of dominant negative (DN) mutants of four Rab proteins that regulate endosomal trafficking was examined. Expression of DN Rab5 and DN Rab11, but not DN Rab7 and DN Rab9, significantly inhibited JEV replication. These results were further tested by silencing Rab5 or Rab11 expression before viral infection. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab11 within 15 min after virus entry, suggesting that after internalization JEV moves to early and recycling endosomes before the release of the viral genome. Our findings demonstrate the roles of Rab5 and Rab11 on JEV infection of BHK-21 cells through the endocytic pathway, providing new insights into the life cycle of flaviviruses.

IMPORTANCE
Although Japanese encephalitis virus (JEV) utilizes different endocytic pathways depending on the cell type being infected, the detailed mechanism of its entry into BHK-21 cells is unknown. Understanding the process of JEV endocytosis and postinternalization will advance our knowledge of JEV infection and pathogenesis as well as provide potential novel drug targets for antiviral intervention. With this objective, we used systematic approaches to dissect this process. The results show that entry of JEV into BHK-21 cells requires a low-pH environment and that the process occurs through dynamin-, actin-, and cholesterol-dependent clathrin-mediated endocytosis that requires Rab5 and Rab11. Our work provides a detailed picture of the entry of JEV into BHK-21 cells and the cellular events that follow.
Development of partial extraction methods to estimate abundance of copper-iron sulphide minerals in the Escondida Norte porphyry copper deposit, Chile
Authors: Preece Richard K. , Williams Martin J. , Gilligan Jonathan M. 
Published: July 2017

Studies were conducted by Minera Escondida, Ltda. (MEL) between 1995 and 2003 to support an investment decision to open Escondida Norte, an enriched porphyry copper deposit adjacent to the Escondida mine and processing facilities. Due to the importance of copper-iron sulphide minerals in predicting metallurgical performance in both process alternatives, a quantitative spatial model of copper-iron sulphide mineral abundances was determined to be a critical study component.
A suite of total and partial copper analyses already in common use was chosen to maximize relative selectivity among the major copper sulphide minerals in the mineral deposit. These analyses were merged with partial and total sulphur analysis and combined with a novel approach to interpret the analytical results as normative mineral estimates of chalcocite, covellite, chalcopyrite and pyrite content. Development and validation of the normative mineral estimates included verification on the analytical stability and reproducibility of the chemical analyses, determination of extraction rates on synthetic mineral standards, and comparison with modal mineral abundance on natural ore samples. Uncertainty of individual normative copper sulphide minerals is estimated at ±5% (95% confidence interval), while uncertainty on pyrite content is ±12%. The uncertainty of the normative mineral estimates are comparable to uncertainty of corresponding modal mineral estimates, and differences between modal and normative estimates are largely within the estimation uncertainty.
While the methods were originally developed for a simple association based on supergene chalcocite ± covellite replacing and overprinting hypogene chalcopyrite + pyrite, subsequent work developed normative mineral models for bornite + chalcopyrite hypogene and mixed copper oxide-sulphide supergene mineralization.
Biochemical, Molecular, and Clinical Characterization of Succinate Dehydrogenase Subunit A Variants of Unknown Significance
Authors: Bannon Amber E. , Kent Jason , Forquer Isaac , Town Ajia , Klug Lillian R. , McCann Kelly , Beadling Carol , Harismendy Oliver , Sicklick Jason K. , Corless Christopher , Shinde Ujwal , Heinrich Michael C. 
Published: July 2017

Abstract
Purpose: Patients who inherit a pathogenic loss-of-function genetic variant involving one of the four succinate dehydrogenase (SDH) subunit genes have up to an 86% chance of developing one or more cancers by the age of 50. If tumors are identified and removed early in these high-risk patients, they have a higher potential for cure. Unfortunately, many alterations identified in these genes are variants of unknown significance (VUS), confounding the identification of high-risk patients. If we could identify misclassified SDH VUS as benign or pathogenic SDH mutations, we could better select patients for cancer screening procedures and remove tumors at earlier stages.
Experimental Design: In this study, we combine data from clinical observations, a functional yeast model, and a computational model to determine the pathogenicity of 22 SDHA VUS. We gathered SDHA VUS from two primary sources: The OHSU Knight Diagnostics Laboratory and the literature. We used a yeast model to identify the functional effect of a VUS on mitochondrial function with a variety of biochemical assays. The computational model was used to visualize variants' effect on protein structure.
Results: We were able to draw conclusions on functional effects of variants using our three-prong approach to understanding VUS. We determined that 16 (73%) of the alterations are actually pathogenic, causing loss of SDH function, and six (27%) have no effect upon SDH function.
Conclusions: We thus report the reclassification of the majority of the VUS tested as pathogenic, and highlight the need for more thorough functional assessment of inherited SDH variants. Clin Cancer Res; 23(21); 6733–43. ©2017 AACR.
Hyperkalemia After Initiating Renin–Angiotensin System Blockade: The Stockholm Creatinine Measurements (SCREAM) Project
Authors: Bandak Ghassan , Sang Yingying , Gasparini Alessandro , Chang Alex R. , Ballew Shoshana H. , Evans Marie , Arnlov Johan , Lund Lars H. , Inker Lesley A. , Coresh Josef , Carrero Juan‐Jesus , Grams Morgan E. 
Published: July 2017

Background

Concerns about hyperkalemia limit the use of angiotensin‐converting enzyme inhibitors (
ACE
‐I) and angiotensin receptor blockers (
ARB
s), but guidelines conflict regarding potassium‐monitoring protocols. We quantified hyperkalemia monitoring and risks after
ACE
‐I/
ARB
initiation and developed and validated a hyperkalemia susceptibility score.

Methods and Results

We evaluated 69 426 new users of
ACE
‐I/
ARB
therapy in the Stockholm Creatinine Measurements (
SCREAM
) project with medication initiation from January 1, 2007 to December 31, 2010, and follow‐up for 1 year thereafter. Three fourths (76%) of
SCREAM
patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity‐matched new
ACE
‐I/
ARB
users to 20 186 new β‐blocker users in
SCREAM
: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β‐blocker and
ACE
‐I/
ARB
users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m
2
were risks higher among
ACE
‐I/
ARB
users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium‐sparing diuretics in new
ACE
‐I/
ARB
users; this score accurately predicted 1‐year hyperkalemia risk in the
SCREAM
cohort (area under the curve, 0.845, 95%
CI
: 0.840–0.869) and in a validation cohort from the
US
‐based Geisinger Health System (N=19 524; area under the curve, 0.818, 95%
CI
: 0.794–0.841), with good calibration.

Conclusions

Hyperkalemia within the first year of
ACE
‐I/
ARB
therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m
2
, but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.
Significant Associations of Neurological Complications of Herpes Zoster With Stroke in Rheumatoid Arthritis Patients
Authors: Liao Tsai‐Ling , Lin Ching‐Heng , Chen Hsin‐Hua , Chen Yi‐Ming , Lin Che‐Chen , Chen Der‐Yuan 
Published: July 2017

Background

Accumulating evidence suggests an increased risk of stroke after herpes zoster (
HZ
). This risk is elevated in immunocompromised patients. The incidence of
HZ
in Asia is higher than in Western countries. However, the epidemiology of
HZ
and
HZ
‐related stroke among rheumatoid arthritis (
RA
) patients in Asia remains unclear.

Methods and Results

We conducted a retrospective cohort study using a population‐based database to investigate the epidemiology of
HZ
in
RA
patients in Taiwan during the period of 2000‐2011. A total of 27 609 newly diagnosed and eligible
RA
cases were identified, and 110 436 non‐
RA
cases were matched for age and sex at a ratio of 4:1.
HZ
risk increased by 2.53‐fold (
P
<0.0001) in
RA
patients compared with the general population. Exposure to corticosteroids (adjusted odds ratio=1.73,
P
<0.0001), adalimumab (adjusted odds ratio=1.61,
P
=0.002), and rituximab (adjusted odds ratio=2.06,
P
=0.008) was associated with an increased risk of
HZ
in
RA
patients. A significant association between the use of methotrexate or corticosteroids and
HZ
risk was dose‐dependent (
P
trend
<0.0001). Elevated risk of stroke was observed in
RA
patients with
HZ
(adjusted hazard ratio=1.27,
P
=0.047), particularly in those with neurological complications (adjusted hazard ratio=1.54,
P
=0.015). A 2.30‐fold significantly increased risk of stroke within 90 days after
HZ
occurrence was observed in
RA
patients compared with those without
HZ
(
P
=0.02). Furthermore, death risk increased in
RA
patients with
HZ
(adjusted hazard ratio=1.18,
P
=0.026).

Conclusions

The risk of
HZ
and
HZ
‐related stroke has increased in
RA
patients. Monitoring the occurrence of
HZ
in
RA
patients and preventing
HZ
‐related stroke or mortality during a specific immunosuppressive therapy are important.
Benign Paroxysmal Positional Vertigo: Management and Its Impact on Falls
Authors: Jumani Kiran , Powell Jason 
Published: July 2017

Introduction: Benign paroxysmal positional vertigo (BPPV) is the most common cause of dizziness in the elderly. This has been identified as a risk factor in falls. Falls are the leading cause of disability and the leading cause of death from injury among people over 75 in the UK. Methods: We assessed the effect of BPPV treatment on falls in an elderly population by retrospectively reviewing one unit’s experience of BPPV management over an 8-year period from June 2008 to June 2016. We specifically assessed patients who were referred for the primary reason of falls and were aged over 65 years. These patients were evaluated and treated with particle repositioning maneuvers if their positional tests were positive. The frequency of falls prior to their visit and at 6-month clinic follow-up were reviewed. Results: The total number of falls in the cohort reduced significantly ( P < .0001) after the procedure, from 128 to 46 falls (64% reduction). Associated comorbidities were also evaluated in this group. Conclusion: A prompt and effective treatment of BPPV is prudent to prevent devastating falls in older people in our communities.
Increased risk of attempted suicide in Australian veterans is associated with total and permanent incapacitation, unemployment and posttraumatic stress disorder severity
Authors: Kerr Katelyn , Romaniuk Madeline , McLeay Sarah , Khoo Andrew , Dent Michael T , Boshen Mark 
Published: July 2017

Background: Military veterans have higher rates of suicidality and completed suicides compared to the general population. Previous research has demonstrated suicidal behaviour is higher in US combat veterans who are younger, suffer from posttraumatic stress disorder, depression and anxiety and score lower on measures of health. However, research on predictors of suicide for Australian veterans is limited. The aim of this study was to identify significant demographic and psychological differences between veterans with posttraumatic stress disorder who had attempted suicide and those with posttraumatic stress disorder who had not, as well as determine predictors of suicide attempts within an Australian cohort. Methods: A retrospective analysis was conducted on 229 ex-service personnel diagnosed with posttraumatic stress disorder who had attended a Military Service Trauma Recovery Day Program as outpatients at Toowong Private Hospital from 2007 to 2014. Patients completed a battery of mental health self-report questionnaires assessing symptoms of posttraumatic stress disorder, alcohol use, anger, depression, anxiety and quality of life. Demographic information and self-reported history of suicide attempts were also recorded. Results: Results indicated the average age was significantly lower, and the rates of posttraumatic stress disorder, anger, anxiety and depression symptoms were significantly higher in those veterans with history of a suicide attempt. Multivariate logistic regression analyses indicated posttraumatic stress disorder symptom severity, unemployment or total and permanent incapacity pension status significantly predicted suicide attempt history. Conclusion: Among a cohort of Australian veterans with posttraumatic stress disorder, psychopathology severity, unemployment and total and permanent incapacity status are significantly associated with suicidality. This study highlights the importance of early identification of posttraumatic stress disorder and psychopathology, therapeutic and social engagement, and prioritisation of tangible employment options or meaningful and goal-directed activities for veterans deemed unable to work.
Differences in Eye Movement Data Recorded by Electro-Oculography and Corneal Reflection Techniques
Authors: Lehtelä Jouni 
Published: July 2017

When the informatory workload is studied using eye-movement technique, the interesting variables are duration of fixations and the number of saccades and blinks. These can be measured by electro-oculography and corneal reflection techniques. To ensure that both methods had the same information source in the study, the equipment was used simultaneously. The source was formed by fixed targets. The subject's head was left free, simulating field conditions. The results of the study indicate that the number of blinks could be determined exactly by either method. With corneal reflection techniques, microsaccades were not found, but saccades were found more easily.
The selection of a retting method for the extraction of bast fibers as response to challenges in composite reinforcement
Authors: Konczewicz Wanda , Zimniewska Małgorzata , Valera Miguel Angel 
Published: July 2017

This article presents an evaluation of bast fiber properties conditioned by the selection of a retting method in terms of meeting requirements for the final application of the fibers as composite reinforcement. Two different methods of fiber extraction were used in the experiment: dew retting and osmotic degumming. The fibrous material was extracted from flax (Modran variety) and hemp (Bialobrzeskie variety). In addition, retted kenaf fibers (from China) were evaluated for the comparison of fiber properties. The properties of the retted and degummed fibers were evaluated according to relevant valid standards regarding color, linear mass, breaking tenacity, aspect ratio, microscopic images and chemical composition, which included the determination of wax and fat, cellulose, hemicellulose, lignin and pectin content and the thermogravimetric analysis coupled with Fourier transform infrared spectroscopy technique. The Attenuated Total Reflection FTIR spectroscopic technique was used for the characterization of the fibers. Also, fogging and volatile organic compound (VOC) emissions were tested in order to evaluate the suitability of the bast fiber for composite formation. The results of the study proved that osmotic degumming applied for bast fiber extraction improves significantly the fiber quality in terms of color, odor, aspect ratio and VOC emission. The aspect ratio of osmotically degummed flax fibers increased by about 46% and hemp fibers by about 22% in comparison with dew-retted fibers. VOC emission of osmotically degummed hemp decreased by about 35%, but in the case of flax fibers, increasing of VOC has been observed. For this reason, osmotically degummed fibers can be recommended as more suitable for composite reinforcement.
Understanding the factors that influence social and community participation as perceived by people with non-traumatic spinal cord injury
Authors: Barclay Linda , Lentin Primrose , McDonald Rachael , Bourke-Taylor Helen 
Published: July 2017

Introduction The number of people with non-traumatic spinal cord injury is rising in developed countries such as Australia and Great Britain. People with non-traumatic spinal cord have different gender, injury and age-related profiles compared to those with traumatically acquired spinal cord injury; therefore, their lived experience is likely to be different. However, the specific issues and challenges that this group faces have not been well investigated. Method Semi-structured in-depth interviews were conducted with 17 adults with non-traumatic spinal cord injury. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Findings The factors that influenced the social and community participation of people with non-traumatic spinal cord injury were grouped into three broad areas: person factors, factors in the physical and institutional environment, and factors in the social or cultural environment. Conclusion The findings from this study inform the understanding of occupational therapists regarding the social and community participation of people with non-traumatic spinal cord injury and how this can be facilitated. Assisting people with non-traumatic spinal cord injury to participate in meaningful social and community-based activities is important to maximise their quality of life.
Electroconvulsive Therapy Training in Canada: A Call for Greater Regulation
Authors: Yuzda Edward , Parker Kathryn , Parker Vivien , Geagea Justin , Goldbloom David 
Published: July 2017

Objective: A national survey of senior psychiatric residents' experience of electroconvulsive therapy (ECT) training was undertaken in Canada in 1989. Since then, guidelines have been published in Canada and the US with respect to ECT training in psychiatry residency programs. This study examines whether there has been any change in the Canadian resident ECT training experience through a second national survey. Methods: Confidential questionnaires assessing the training in and the attitudes toward ECT were sent to all 133 psychiatric residents in their final year of training in Canadian medical schools. Results: We attained a response rate of 68.3%. Of respondents, 88% felt that theoretical and practical ECT training should be a mandatory component of psychiatric residency programs. No marked improvements have occurred with respect to didactic and bedside training in ECT, compared with the original 1989 study. Only 18% of respondents reported that they feel completely competent administering ECT. Despite this, 59.3% anticipate working in an inpatient setting. Conclusions: The publication of training guidelines has made little impact on training in and attitudes toward ECT in senior psychiatric residents in Canada. Despite senior residents' acknowledgement of ECT's value, few feel competent to administer ECT after completing their training.
Bipolar II Disorder: An Overview of Recent Developments
Authors: Hadjipavlou George , Mok Hiram , Yatham Lakshmi N 
Published: July 2017

Objective: Recent research on the epidemiology, clinical course, diagnosis, and treatment of bipolar II disorder (BD II) stands to have a considerable impact on clinical practice. This paper reviews these developments. Method: We conducted a Pubmed search, focusing on the period from January 1, 1994, to August 31, 2004. Articles deemed directly relevant to the epidemiology, course, diagnosis, and management of BD II were considered. Results: The prevalence of BD II is likely higher than previously suggested. Systematic probing for particular clinical features and use of screening tools allow for a more timely and accurate detection of the disorder. There is a paucity of good quality data to guide clinicians treating BD II. Conclusion: Significant progress has been made in clarifying diagnostic and treatment issues in BD II. Neither strong nor broad treatment recommendations can be made; a cautious interpretation of available data suggests that lithium or lamotrigine are fairly reasonable first-line choices. More well-designed studies with larger samples are needed to improve the evidence base for managing this disorder.
The Centre for Addiction and Mental Health Concurrent Disorders Screener
Authors: Negrete Juan C , Collins Jane , Turner Nigel E , Skinner Wayne 
Published: July 2017

Objectives: To review the characteristics of psychiatric screening tools currently available in addiction treatment services for rapid assessment of comorbid pathology and to introduce the Centre for Addictions and Mental Health Concurrent Disorders Screener (CAMH-CDS), a computer-administered questionnaire that screens for the occurrence of 11 Axis I disorders plus all substance use disorders, as well as for a history of conduct disorder. Methods: We describe the structure, contents, and application of the CAMH-CDS. We undertook a sensitivity and specificity trial involving 171 subjects, a test–retest reliability study with 301 participants, and an open-label concordance study with 656 respondents. All subjects were regular clients of a major addiction treatment facility. Results: The CAMH-CDS was easily and effectively used by addiction counsellors with limited or no mental health training. It has a low rate of false-negative responses, and it yields excellent test–retest reliability figures. It is highly sensitive to identifying persons with psychiatric disturbances; however, its ability to discriminate among specific disorders appears to be more limited. Conclusions: The CAMH-CDS can be reliably used to rule out the presence of psychiatric comorbidity in addiction service populations. As with other psychiatric screening instruments, its sensitivity values are stronger than its specificity values. The use of nonstructured clinical evaluations as the gold standard for diagnosis and a likely variance in the patients' symptom reports between the 2 examinations may have contributed to the latter finding.