bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annexin A2 Mediates the Localization of Measles Virus Matrix Protein at the Plasma Membrane
Authors: Koga Ritsuko , Kubota Marie , Hashiguchi Takao , Yanagi Yusuke , Ohno Shinji 
Published: March 2018

ABSTRACT

Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca
2+
-dependent manner. Annexin A2 (AnxA2), a member of this family, has been implicated in a variety of cellular functions, including the organization of membrane domains, vesicular trafficking, and cell-cell adhesion. AnxA2 generally forms a heterotetrameric complex with a small Ca
2+
-binding protein, S100A10. Measles virus (MV), a member of the family
Paramyxoviridae
, is an enveloped virus with a nonsegmented negative-strand RNA genome. Knockdown of AnxA2 greatly reduced MV growth in cells without affecting its entry and viral RNA production. In MV-infected, AnxA2 knockdown cells, the expression level of the matrix (M) protein, but not other viral proteins, was reduced compared with that in control cells, and the distribution of the M protein at the plasma membrane was decreased. The M protein lines the inner surface of the envelope and plays an important role in virus assembly by connecting the nucleocapsid to the envelope proteins. The M protein bound to AnxA2 independently of AnxA2's phosphorylation or its association with S100A10 and was colocalized with AnxA2 within cells. Truncation of the N-terminal 10 amino acid residues, but not the N-terminal 5 residues, compromised the ability of the M protein to interact with AnxA2 and localize at the plasma membrane. These results indicate that AnxA2 mediates the localization of the MV M protein at the plasma membrane by interacting with its N-terminal region (especially residues at positions 6 to 10), thereby aiding in MV assembly.

IMPORTANCE
MV is an important human pathogen, still claiming ∼100,000 lives per year despite the presence of effective vaccines, and it causes occasional outbreaks even in developed countries. Replication of viruses largely relies on the functions of host cells. Our study revealed that the reduction of the host protein annexin A2 compromises the replication of MV within the cell. Further studies demonstrated that annexin A2 interacts with the MV M protein and mediates the localization of the M protein at the plasma membrane where MV particles are formed. The M protein lines the inner surface of the MV envelope membrane and plays a role in MV particle formation. Our results provide useful information for the understanding of the MV replication process and potential development of antiviral agents.
Systematic review of clinical practice guidelines to identify recommendations for rehabilitation after stroke and other acquired brain injuries
Authors: Jolliffe Laura , Lannin Natasha A , Cadilhac Dominique A , Hoffmann Tammy 
Published: February 2018

ObjectivesRehabilitation clinical practice guidelines (CPGs) contain recommendation statements aimed at optimising care for adults with stroke and other brain injury. The aim of this study was to determine the quality, scope and consistency of CPG recommendations for rehabilitation covering the acquired brain injury populations.DesignSystematic review.InterventionsIncluded CPGs contained recommendations for inpatient rehabilitation or community rehabilitation for adults with an acquired brain injury diagnosis (stroke, traumatic or other non-progressive acquired brain impairments). Electronic databases (n=2), guideline organisations (n=4) and websites of professional societies (n=17) were searched up to November 2017. Two independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and textual syntheses were used to appraise and compare recommendations.ResultsFrom 427 papers screened, 20 guidelines met the inclusion criteria. Only three guidelines were rated high (>75%) across all domains of AGREE-II; highest rated domains were ‘scope and purpose’ (85.1, SD 18.3) and ‘clarity’ (76.2%, SD 20.5). Recommendations for assessment and for motor therapies were most commonly reported, however, varied in the level of detail across guidelines.ConclusionRehabilitation CPGs were consistent in scope, suggesting little difference in rehabilitation approaches between vascular and traumatic brain injury. There was, however, variability in included studies and methodological quality.PROSPERO registration numberCRD42016026936.
Exploiting science? A systematic analysis of complementary and alternative medicine clinic websites’ marketing of stem cell therapies
Authors: Murdoch Blake , Zarzeczny Amy , Caulfield Timothy 
Published: February 2018

ObjectiveTo identify the frequency and qualitative characteristics of stem cell-related marketing claims made on websites of clinics featuring common types of complementary and alternative medicine practitioners. The involvement of complementary and alternative medicine practitioners in the marketing of stem cell therapies and stem cell-related interventions is understudied. This research explores the extent to which they are involved and collaborate with medical professionals. This knowledge will help with identifying and evaluating potential policy responses to this growing market.DesignSystematic website analysis.SettingGlobal. US and English-language bias due to methodology.Main outcome measuresRepresentations made on clinic websites in relation to practitioner types, stem cell therapies and their targets, stem cell-related interventions. Statements about stem cell therapies relating to evidence of inefficacy, limited evidence of efficacy, general procedural risks, risks specific to the mode of therapy, regulatory status, experimental or unproven nature of therapy. Use of hype language (eg, language that exaggerates potential benefits).Results243 websites offered stem cell therapies. Many websites advertised stem cell transplantation from multiple sources, such as adipose-derived (112), bone marrow-derived (100), blood-derived (28), umbilical cord-derived (26) and others. Plant stem cell-based treatments and products (20) were also advertised. Purposes for and targets of treatment included pain, physical injury, a wide range of diseases and illnesses, cosmetic concerns, non-cosmetic ageing, sexual enhancement and others. Medical doctors (130), chiropractors (53) and naturopaths (44) commonly work in the clinics we found to be offering stem cell therapies. Few clinic websites advertising stem cell therapies included important additional information, including statements about evidence of inefficacy (present on only 12.76% of websites), statements about limited evidence of efficacy (18.93%), statements of general risks (24.69%), statements of risks specific to the mode(s) of therapy (5.76%), statements as to the regulatory status of the therapies (30.86%) and statements that the therapy is experimental or unproven (33.33%). Hype language was noted (31.69%).ConclusionsStem cell therapies and related interventions are marketed for a wide breadth of conditions and are being offered by complementary and alternative practitioners, often in conjunction with medical doctors. Consumer protection and truth-in-advertising regulation could play important roles in addressing misleading marketing practices in this area.
Effectiveness of postdischarge interventions for reducing the severity of chronic pain after total knee replacement: systematic review of randomised controlled trials
Authors: Wylde Vikki , Dennis Jane , Gooberman-Hill Rachael , Beswick Andrew David 
Published: February 2018

ObjectiveApproximately 20% of patients experience chronic pain after total knee replacement (TKR). The aim of this systematic review was to evaluate the effectiveness of postdischarge interventions commenced in the first 3 months after surgery in reducing the severity of chronic pain after TKR.DesignThe protocol for this systematic review was registered on PROSPERO (registration number: CRD42017041382). MEDLINE, Embase, CINAHL, PsycINFO and The Cochrane Library were searched from inception to November 2016. Randomised controlled trials of postdischarge intervention which commenced in the first 3 months after TKR surgery were included. The primary outcome of the review was self-reported pain severity at 12 months or longer after TKR. Risk of bias was assessed using the Cochrane risk-of-bias tool.ResultsSeventeen trials with data from 2485 randomised participants were included. The majority of trials evaluated physiotherapy interventions (n=13); other interventions included nurse-led interventions (n=2), neuromuscular electrical stimulation (n=1) and a multidisciplinary intervention (n=1). Opportunities for meta-analysis were limited by heterogeneity. No study found a difference in long-term pain severity between trial arms, with the exception of one trial which found home-based functional exercises aimed at managing kinesiophobia resulted in lower pain severity scores at 12 months postoperatively compared with advice to stay active.ConclusionThis systematic review and narrative synthesis found no evidence that one type of physiotherapy intervention is more effective than another at reducing the severity of chronic pain after TKR. Further research is needed to evaluate non-physiotherapy interventions, including the provision of care as part of a stratified and multidisciplinary care package.PROSPERO registration numberCRD42017041382.
TRPM2 Mediates Neutrophil Killing of Disseminated Tumor Cells
Authors: Gershkovitz Maya , Caspi Yaki , Fainsod-Levi Tanya , Katz Ben , Michaeli Janna , Khawaled Saleh , Lev Shaya , Polyansky Lola , Shaul Merav E. , Sionov Ronit V. , Cohen-Daniel Leonor , Aqeilan Rami I. , Shaul Yoav D. , Mori Yasuo , Karni Rotem , Fridlender Zvi G. , Binshtok Alexander M. , Granot Zvi 
Published: February 2018

AbstractNeutrophils play a critical role in cancer, with both protumor and antitumor neutrophil subpopulations reported. The antitumor neutrophil subpopulation has the capacity to kill tumor cells and limit metastatic spread, yet not all tumor cells are equally susceptible to neutrophil cytotoxicity. Because cells that evade neutrophils have greater chances of forming metastases, we explored the mechanism neutrophils use to kill tumor cells. Neutrophil cytotoxicity was previously shown to be mediated by secretion of H2O2. We report here that neutrophil cytotoxicity is Ca2+ dependent and is mediated by TRPM2, a ubiquitously expressed H2O2-dependent Ca2+ channel. Perturbing TRPM2 expression limited tumor cell proliferation, leading to attenuated tumor growth. Concomitantly, cells expressing reduced levels of TRPM2 were protected from neutrophil cytotoxicity and seeded more efficiently in the premetastatic lung.Significance: These findings identify the mechanism utilized by neutrophils to kill disseminated tumor cells and to limit metastatic spread. Cancer Res; 78(10); 2680–90. ©2018 AACR.
Molecular Alterations and Buparlisib Efficacy in Patients with Squamous Cell Carcinoma of the Head and Neck: Biomarker Analysis from BERIL-1
Authors: Soulières Denis , Licitra Lisa , Mesía Ricard , Remenár Éva , Li Shau-Hsuan , Karpenko Andrey , Chol Marie , Wang Ying A. , Solovieff Nadia , Bourdeau Laurence , Sellami Dalila , Faivre Sandrine 
Published: February 2018

Abstract
Purpose: The preplanned exploratory analysis of the BERIL-1 trial presented here aimed to identify biomarkers of response to the combination of buparlisib and paclitaxel.
Patients and Methods: BERIL-1 was a multicenter, randomized, double-blind, placebo-controlled phase II study. Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) progressing on/after one previous platinum-based chemotherapy regimen in the recurrent or metastatic setting were treated with either buparlisib plus paclitaxel or placebo plus paclitaxel. Archival tumor tissue and ctDNA samples were analyzed for molecular alterations and immune infiltration using next-generation sequencing or immunohistochemistry.
Results: Biomarker analyses were performed in randomized patients (n = 158) with available biomarker data. The most frequently (&gt;5%) mutated genes were TP53, FAT1, TET2, KMT2D, PIK3CA, NOTCH1, NFE2L2, NOTCH2, CCND1, and CDKN2A. Patients with SCCHN tumors (from various primary sites) having HPV-negative status (HR = 0.51), TP53 alterations (HR = 0.55) or low mutational load (HR = 0.57) derived overall survival (OS) benefit with the combination of buparlisib and paclitaxel. OS benefit with this combination was also increased in patients with presence of intratumoral TILs ≥10% (HR = 0.51), stromal TILs ≥15% (HR = 0.53), intratumoral CD8-positive cells ≥5% (HR = 0.45), stromal CD8-positive cells ≥10% (HR = 0.47), or CD8-positive cells in invasive margins &gt;25% (HR = 0.37). A trend for improved progression-free survival with the combination of buparlisib and paclitaxel was also observed in these patients.
Conclusions: The BERIL-1 biomarker analyses showed that patients with TP53 alterations, HPV-negative status, low mutational load, or high infiltration of TILs or CD8-positive cells derived survival benefit with the combination of buparlisib and paclitaxel. Clin Cancer Res; 24(11); 2505–16. ©2018 AACR.
Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood
Authors: Alexander Peta M.A. , Nugent Alan W. , Daubeney Piers E.F. , Lee Katherine J. , Sleeper Lynn A. , Schuster Tibor , Turner Christian , Davis Andrew M. , Semsarian Chris , Colan Steven D. , Robertson Terry , Ramsay James , Justo Robert , Sholler Gary F. , King Ingrid , Weintraub Robert G. ,   On behalf of the National Australian Childhood Cardiomyopathy Study
Published: February 2018

Background:
Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy.

Methods:
The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0–10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation.

Results:

There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0–92.0) 1 year after presentation, 80% (95% CI, 69.0–87.0) at 10 years, and 78% (95% CI, 67.0–86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60–11.05;
P
=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02–8.08;
P
=0.045), higher posterior wall thickness
z
score (hazard ratio, 1.45; 95% CI, 1.22–1.73;
P
<0.001), and lower fractional shortening
z
score (hazard ratio, 0.84; 95% CI, 0.74–0.95;
P
=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with β-blocker, and 13 (21%) had an implantable cardioverter-defibrillator.

Conclusions:
The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.
Walter Orr Roberts Lecture
Authors: Dickinson Robert E. 
Published: February 2018

This paper, as the written version of the 1995 AMS Walter Orr Roberts Lecture, provides an overview of the current status of the inclusion of land surface processes in climate models. These processes provide fluxes of water and energy to atmospheric models and help determine surface meteorology and climate over the continents. With the increasing complexity and importance of these parameterizations and their detailed treatments of the roles of soils and vegetation have come greater demands for observational programs to evaluate their success and to provide required parameters. Intercomparisons between different land models are also becoming increasingly valuable as a means of identifying their weaknesses and limitations.
The paper especially highlights the need for further emphasis on the coupling between land and the atmosphere in models. In particular, it calls for further evolution and improvement of the model treatments of precipitation, cloud effects on surface radiation, and boundary layer processes.
Importance of Late Fall ENSO Teleconnection in the Euro-Atlantic Sector
Authors: King Martin P. , Herceg-Bulić Ivana , Bladé Ileana , García-Serrano Javier , Keenlyside Noel , Kucharski Fred , Li Camille , Sobolowski Stefan 
Published: March 2018

AbstractRecent studies have indicated the importance of fall climate forcings and teleconnections in influencing the climate of the northern mid- to high latitudes. Here, we present some exploratory analyses using observational data and seasonal hindcasts, with the aim of highlighting the potential of the El Niño–Southern Oscillation (ENSO) as a driver of climate variability during boreal late fall and early winter (November and December) in the North Atlantic–European sector, and motivating further research on this relatively unexplored topic. The atmospheric ENSO teleconnection in November and December is reminiscent of the east Atlantic pattern and distinct from the well-known arching extratropical Rossby wave train found from January to March. Temperature and precipitation over Europe in November are positively correlated with the Niño-3.4 index, which suggests a potentially important ENSO climate impact during late fall. In particular, the ENSO-related temperature anomaly extends over a much larger area than during the subsequent winter months. We discuss the implications of these results and pose some research questions.
Voluntary- and Involuntary-Distraction Engagement: An Exploratory Study of Individual Differences
Authors: Chen Huei-Yen Winnie , Hoekstra-Atwood Liberty , Donmez Birsen 
Published: February 2018

Objective The aim of this study was to explore individual differences in voluntary and involuntary driver-distraction engagement. Background Distractions may stem from intentional engagement in secondary tasks (voluntary) or failing to suppress non-driving-related stimuli or information (involuntary). A wealth of literature has examined voluntary distraction; involuntary distraction is not particularly well understood. Individual factors, such as age, are known to play a role in how drivers engage in distractions. However, it is unclear which individual factors are associated with voluntary- versus involuntary-distraction engagement and whether there is a relation between how drivers engage in these two distraction types. Method Thirty-six participants, ages 25 to 39, drove in a simulator under three conditions: voluntary distraction with a self-paced visual-manual task on a secondary display, involuntary distraction with abrupt onset of irrelevant visual-audio stimuli on the secondary display, and no distraction. Results The number of glances toward the secondary display under voluntary distraction was not correlated to that under involuntary distraction. The former was associated with gender, age, annual mileage, and self-reported distraction engagement; such associations were not observed for the latter. Accelerator release time in response to lead-vehicle braking was delayed similarly under both conditions. Conclusion Propensity to engage in voluntary distractions appears to be not related to the inability of suppressing involuntary distractions. Further, voluntary and involuntary distraction both affect braking response. These findings have implications for design of in-vehicle technologies, which may be sources of both distraction types.
Amelioration of right ventricular systolic function and stiffness in a patient with idiopathic pulmonary arterial hypertension treated with oral triple combination therapy
Authors: Nakaya Toshitaka , Tsujino Ichizo , Ohira Hiroshi , Sato Takahiro , Watanabe Taku , Oyama‐Manabe Noriko , Nishimura Masaharu 
Published: February 2018

Right ventricular (RV) function is an important determinant of the prognosis in patients with pulmonary arterial hypertension (PAH). In the context of recent therapeutic progress, there is an increasing need for better monitoring of RV function for management of PAH. We present the case of a 42‐year‐old woman with idiopathic PAH who was treated with three oral pulmonary vasodilators, i.e. tadalafil, ambrisentan, and beraprost. At the baseline assessment, the mean pulmonary arterial pressure (mPAP) was 45 mmHg, cardiac index (CI) was 1.36 L/min/m2, and pulmonary vascular resistance (PVR) was elevated to 21.3 Wood units (WU). However, three months after the start of combination treatment, mPAP and PVR decreased to 42 mmHg and 7.5 WU, respectively, and conventional indices of RV function, such as CI, right atrial area, and right atrial pressure also improved. Beyond three months, however, there were no further improvements in mPAP, PVR, or indices of RV function. In addition, we calculated three recently introduced indices of intrinsic RV function: end‐systolic elastance (Ees; an index of RV contractility), Ees/arterial elastance ratio (Ees/Ea; an index of RV/pulmonary arterial coupling), and β (an index of RV stiffness) using cardiac magnetic resonance imaging and Swan‐Ganz catheterization measurements. Notably, in contrast to conventional parameters, Ees, Ees/Ea, and β showed persistent improvement during the entire two‐year follow‐up. The application of Ees, Ees/Ea, and β may play an additional role in a comprehensive assessment of RV function in PAH.
Reverse shoulder arthroplasty for the treatment of acute complex proximal humeral fractures: Influence of greater tuberosity healing on the functional outcomes
Authors: Torrens Carlos , Alentorn-Geli Eduard , Mingo Felipe , Gamba Carlo , Santana Fernando 
Published: February 2018

Purpose: To investigate the influence of greater tuberosity healing on the functional outcomes of reverse shoulder arthroplasty (RSA) for the treatment of acute complex proximal humeral fractures (PHFs), and to investigate the influence of patient- and surgery-related factors in the healing of the greater tuberosity. Methods: Retrospective study including 41 consecutive PHFs treated using RSA with minimum 2-year follow-up. In all the cases, tuberosities were reattached with a standardized technique. All the patients were assessed at the last follow-up with constant score. Body mass index, surgery delay, comorbidities, polyethylene size, glenosphere size, overhanging of glenosphere, and scapular notch were recorded, and their influence in final constant score and in greater tuberosity healing was analyzed. Results: Mean final constant score was of 60.7 points (standard deviation (SD) = 9.9). Greater tuberosity healed in proper position in 68% of the cases. There were no significant differences in constant score between patients with (mean = 61; SD = 9.5) and without (mean = 61; SD = 11.3) the healing of greater tuberosity. All patients scored above 90° in forward elevation. Scapular notch was reported in 14.6% of the cases. Age significantly affected the constant score ( p = 0.008). Comorbidities significantly interfered with greater tuberosity healing ( p = 0.03). There was one reoperation after dislocation. Conclusion: In spite of expecting good functional outcome with low complication rate after RSA for acute PHFs, the influence of greater tuberosity healing on shoulder function could not be demonstrated. The presence of comorbidities, but not age or gender, negatively influenced the healing of the greater tuberosity.
Human herpesvirus 6 viremia affects T-cell reconstitution after allogeneic hematopoietic stem cell transplantation
Authors: de Koning Coco , Admiraal Rick , Nierkens Stefan , Boelens Jaap Jan 
Published: February 2018

Key PointsOnly high HHV6 viremia (>105 copies/mL) affects late but not early T-cell reconstitution after HCT. Antivirals improve T-cell reconstitution probability in the context of HHV6 viremia after HCT.