bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerobic Fitness and Habitual Physical Activity in Frail and Nonfrail Community-Dwelling Elderly
Authors: Bastone Alessandra de Carvalho , Ferriolli Eduardo , Teixeira Claudine Patricia , Dias João Marcos Domingues , Dias Rosângela Corrêa 
Published: November 2014

Background:Self-reported measures of decreased aerobic fitness and low physical activity are criteria of frailty. However, research assessing aerobic fitness and physical activity levels associated with frailty is limited. Therefore, the aims of this study were to objectively assess the aerobic fitness and the physical activity level of frail and nonfrail elderly, and to examine the association between frailty, aerobic fitness and habitual physical activity.Methods:This study included 26 elderly (66 to 86 years), randomly selected. The groups (frail/nonfrail) were age and sex paired. Peak oxygen consumption, maximal walking distance and speed were assessed during the incremental shuttle walk test (ISWT). Average daily time spent in sedentary, light, moderate and hard activity, counts, number of steps and energy expenditure were measured by accelerometry.Results:All variables measured by the ISWT and accelerometer differed significantly between the groups (P < .02). All aerobic fitness and physical activity variables were significantly associated with frailty, independent of the number of chronic health conditions (P < .05).Conclusions:Frailty is associated with low peak oxygen consumption and low physical activity level. These findings could guide future clinical trials designed to evaluate the efficacy of aerobic exercises in the prevention and treatment of frailty.
A General Method for Rapid Determination of Antibiotic Susceptibility and Species in Bacterial Infections
Authors: Mezger Anja , Gullberg Erik , Göransson Jenny , Zorzet Anna , Herthnek David , Tano Eva , Nilsson Mats , Andersson Dan I. 
Published: November 2014

ABSTRACT

To ensure correct antibiotic treatment and reduce the unnecessary use of antibiotics, there is an urgent need for new rapid methods for species identification and determination of antibiotic susceptibility in infectious pathogenic bacteria. We have developed a general method for the rapid identification of the bacterial species causing an infection and the determination of their antibiotic susceptibility profiles. An initial short cultivation step in the absence and presence of different antibiotics was combined with sensitive species-specific padlock probe detection of the bacterial target DNA to allow a determination of growth (i.e., resistance) and no growth (i.e., susceptibility). A proof-of-concept was established for urinary tract infections in which we applied the method to determine the antibiotic susceptibility profiles of
Escherichia coli
for two drugs with 100% accuracy in 3.5 h. The short assay time from sample to readout enables fast appropriate treatment with effective drugs and minimizes the need to prescribe broad-spectrum antibiotics due to unknown resistance profiles of the treated infection.
Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients
Authors: Larrat Sylvie , Kulkarni Om , Claude Jean-Baptiste , Beugnot Réjane , Blum Michaël G. B. , Fusillier Katia , Lupo Julien , Tremeaux Pauline , Plages Agnès , Marlu Alice , Duborjal Hervé , Signori-Schmuck Anne , Francois Olivier , Zarski Jean-Pierre , Morand Patrice , Leroy Vincent 
Published: November 2014

ABSTRACT

Despite the gain in sustained virological responses (SVR) provided by protease inhibitors (PIs), failures still occur. The aim of this study was to determine if a baseline analysis of the NS3 region using ultradeep pyrosequencing (UDPS) can help to predict an SVR. Serum samples from 40 patients with previously nonresponding genotype 1 chronic hepatitis C who were retreated with triple therapy, including a PI, were analyzed. Baseline UDPS of the NS3 gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Mutations conferring resistance to PIs were sought. The overall diversity of the quasispecies was evaluated by calculating the Shannon entropy (SE). Resistance mutations were found in plasma and PBMC but were not discriminating enough to predict an SVR. NS3 quasispecies heterogeneity was significantly lower at baseline in patients achieving an SVR than in those not achieving an SVR (SE of 26.98 ± 16.64 × 10
−3
versus 44.93 ± 19.58 × 10
−3
,
P
= 0.0047). With multivariate analysis, the independent predictors of an SVR were fibrosis of stage F ≤2 (odds ratio [OR], 13.3; 95% confidence interval [CI], 1.25 to 141.096;
P
< 0.03) and SE below the median (OR, 5.4; 95% CI, 1.22 to 23.87;
P
< 0.03). More than the presence of minor mutations at the baseline in plasma or in PBMC, the NS3 viral heterogeneity determined by UDPS is an independent factor for an SVR in previously treated patients receiving triple therapy that includes a PI.
Identification and Mutagenesis of the Adeno-Associated Virus 5 Sialic Acid Binding Region
Authors: Afione Sandra , DiMattia Michael A. , Halder Sujata , Di Pasquale Giovanni , Agbandje-McKenna Mavis , Chiorini John A. 
Published: November 2014

ABSTRACT

As a genus, the dependoviruses use a diverse group of cell surface carbohydrates for attachment and entry. Despite the fact that a majority of adeno-associated viruses (AAVs) utilize sialic acid (SIA) for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, two SIA binding regions were mapped for AAV5. The first site mapped to the depression in the center of the 3-fold axis of symmetry, while the second site was located under the βHI loop close to the 5-fold axis. Mutagenesis of amino acids 569 and 585 or 587 within the 3-fold depression resulted in elimination or alteration in SIA-dependent transduction, respectively. This change in SIA binding was confirmed using glycan microarrays. Mutagenesis of the second site identified a role in transduction that was SIA independent. Further studies of the mutants at the 3-fold site demonstrated a change in transduction activity and cell tropism
in vivo
as well as resistance to neutralization by a polyclonal antibody raised against the wild-type virus.

IMPORTANCE
Despite the fact that a majority of AAVs utilize sialic acid for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, the sialic acid binding regions of AAV5 were identified and studied using a variety of approaches. Mutagenesis of this region resulted in elimination or alteration in sialic acid-dependent transduction in cell lines. This change in sialic acid glycan binding was confirmed using glycan arrays. Further study also demonstrated a change in transduction and activity and cell tropism
in vivo
as well as resistance to neutralization by antibodies raised against the wild-type virus.
The Large Tegument Protein pUL36 Is Essential for Formation of the Capsid Vertex-Specific Component at the Capsid-Tegument Interface of Herpes Simplex Virus 1
Authors: Fan Wan H. , Roberts Ashley P. E. , McElwee Marion , Bhella David , Rixon Frazer J. , Lauder Rebecca 
Published: November 2014

ABSTRACT
Herpesviruses have a characteristic particle structure comprising an icosahedral capsid, which contains the DNA genome and is, in turn, surrounded by a proteinaceous tegument layer and a lipid envelope. In herpes simplex virus, the interaction between the capsid and tegument is limited to the capsid vertices and involves two minor capsid proteins, pUL17 and pUL25, and the large inner tegument protein pUL36. pUL17 and pUL25 form a heterodimeric structure, the capsid vertex-specific component (CVSC), that lies on top of the peripentonal triplexes, while pUL36 has been reported to connect the CVSC to the penton. In this study, we used virus mutants with deletions in the genes for pUL36 and another inner tegument protein, pUL37, to analyze the contributions of these proteins to CVSC structure. Using electron cryomicroscopy and icosahedral reconstruction of mutants that express pUL17 and pUL25 but not pUL36, we showed that in contrast to accepted models, the CVSC is not formed from pUL17 and pUL25 on their own but requires a contribution from pUL36. In addition, the presence of full-length pUL36 results in weak density that extends the CVSC toward the penton, suggesting either that this extra density is formed directly by pUL36 or that pUL36 stabilizes other components of the vertex-tegument interface.

IMPORTANCE
Herpesviruses have complex particles that are formed as a result of a carefully controlled sequence of assembly steps. The nature of the interaction between two of the major particle compartments, the icosahedral capsid and the amorphous tegument, has been extensively studied, but the identity of the interacting proteins and their roles in forming the connections are still unclear. In this study, we used electron microscopy and three-dimensional reconstruction to analyze virus particles formed by mutants that do not express particular interacting proteins. We show that the largest viral protein, pUL36, which occupies the layer of tegument closest to the capsid, is essential for formation of structurally normal connections to the capsid. This demonstrates the importance of pUL36 in the initial stages of tegument addition and provides new insights into the process of virus particle assembly.
Inconsistent condom use by male clients during anal intercourse with occasional and regular female sex workers (FSWs): survey findings from southern states of India
Authors: Ramanathan Shreena , Nagarajan Karikalan , Ramakrishnan Lakshmi , Mainkar Mandar K , Goswami Prabuddhagopal , Yadav Diwakar , Sen Shrabanti , George Bitra , Rachakulla Harikumar , Subramanian Thilakavathi , Paranjape Ramesh S 
Published: November 2014

ObjectivesSelf-reported anal intercourse by female sex workers (FSWs) documented in recent studies from India range between 11.9% and 22%. However, comparable data on anal intercourse and condom use from male clients of FSWs is lacking. Using data from a bio-behavioural survey (2009–2010), we examined prevalence of anal intercourse, male clients’ self-reported inconsistent condom use during anal intercourse with FSWs, and correlates of this behaviour in India's high HIV prevalence southern states (Andhra Pradesh, Maharashtra and Tamil Nadu combined).MethodsUsing two-stage time location cluster sampling, we recruited 4803 clients of FSWs, ages 18–60 years, who had purchased sex from an FSW in the past month. After obtaining informed consent, respondents were interviewed and tested for HIV and sexually transmitted infections (syphilis, gonorrhoea and chlamydia). Logistic regression analysis was used to identify the factors associated with inconsistent condom use during anal intercourse (in the past 6 months) with FSWs.ResultsOverall, 12.3% clients reported anal intercourse in the past 6 months, of whom 48.4% used condoms inconsistently. Clients of FSWs who were ages 26 years or older (AOR 2.68, p=0.032); employed as manual labourers (AOR 2.43, p=0.013); consumed alcohol (AOR 2.63, p=0.001); reported five or more sex acts with FSWs in the past month (AOR 2.53, p=0.031); and perceived themselves to be at higher risk for HIV (AOR 4.82, p=0.001) were more likely to inconsistently use condoms during anal intercourse.ConclusionsThe results suggest that sex workers and their clients commonly practice anal intercourse, but a relatively high proportion of clients do not consistently use condoms, leading to a greater risk of acquiring HIV and its further transmission to other male and female sexual partners. Given the multidirectional risk, safer sex communication on heterosexual anal intercourse must be incorporated into HIV prevention programmes.
Classification of osteoarthritis phenotypes by metabolomics analysis
Authors: Zhang Weidong , Likhodii Sergei , Zhang Yuhua , Aref-Eshghi Erfan , Harper Patricia E , Randell Edward , Green Roger , Martin Glynn , Furey Andrew , Sun Guang , Rahman Proton , Zhai Guangju 
Published: November 2014

ObjectivesTo identify metabolic markers that can classify patients with osteoarthritis (OA) into subgroups.DesignA case-only study design was utilised.ParticipantsPatients were recruited from those who underwent total knee or hip replacement surgery due to primary OA between November 2011 and December 2013 in St. Clare's Mercy Hospital and Health Science Centre General Hospital in St. John's, capital of Newfoundland and Labrador (NL), Canada. 38 men and 42 women were included in the study. The mean age was 65.2±8.7 years.Outcome measuresSynovial fluid samples were collected at the time of their joint surgeries. Metabolic profiling was performed on the synovial fluid samples by the targeted metabolomics approach, and various analytic methods were utilised to identify metabolic markers for classifying subgroups of patients with OA. Potential confounders such as age, sex, body mass index (BMI) and comorbidities were considered in the analysis.ResultsTwo distinct patient groups, A and B, were clearly identified in the 80 patients with OA. Patients in group A had a significantly higher concentration on 37 of 39 acylcarnitines, but the free carnitine was significantly lower in their synovial fluids than in those of patients in group B. The latter group was further subdivided into two subgroups, that is, B1 and B2. The corresponding metabolites that contributed to the grouping were 86 metabolites including 75 glycerophospholipids (6 lysophosphatidylcholines, 69 phosphatidylcholines), 9 sphingolipids, 1 biogenic amine and 1 acylcarnitine. The grouping was not associated with any known confounders including age, sex, BMI and comorbidities. The possible biological processes involved in these clusters are carnitine, lipid and collagen metabolism, respectively.ConclusionsThe study demonstrated that OA consists of metabolically distinct subgroups. Identification of these distinct subgroups will help to unravel the pathogenesis and develop targeted therapies for OA.
Origin and status of the Gran Sasso INFN Laboratory
Authors: Votano Lucia 
Published: November 2014

The Gran Sasso National Laboratory of INFN (LNGS) is the largest underground laboratory for astroparticle physics in the world. Located in Italy between the cities of L'Aquila and Teramo, 120 km far from Rome, is a research infrastructure mainly dedicated to astroparticle and neutrino physics. It offers the most advanced underground facility in terms of dimensions, complexity and completeness of its infrastructures. LNGS is one of the four national laboratories run by the Istituto Nazionale di Fisica Nucleare (INFN).The scientific program at LNGS is mainly focused on astroparticle, particle and nuclear physics. The laboratory presently hosts many experiments as well as R&D activities, including world-leading research in the fields of solar neutrinos, accelerator neutrinos (CNGS neutrino beam from CERN to Gran Sasso), dark matter (DM), neutrinoless double beta decay (2β0ν) and nuclear cross-section of astrophysical interest. Associate sciences like earth physics, biology and fundamental physics complement the activities. The laboratory is operated as an international science facility and hosts experiments whose scientific merit is assessed by an international advisory Scientific Committee.A review of the main experiments carried out at LNGS will be given, together with the most recent and relevant scientific results achieved.
Health-Related Quality of Life of Rural Clients Seeking Telepsychology Services
Authors: Tarlow Kevin R. , McCord Carly E. , Elliott Timothy R. , Brossart Daniel F. 
Published: November 2014

Sixty million US residents live in rural areas, but health policies and interventions developed from an urban mindset often fail to address the significant barriers to health experienced by these local communities. Telepsychology, or psychological services delivered by distance via technology, is an emerging treatment modality with special implications for underserved rural areas. This study found that a sample of rural residents seeking telepsychology services(n=94)had low health-related quality of life (HRQOL), often due to cooccurring physical and mental health diagnoses including high rates of depression. However, a brief telepsychology treatment delivered to rural clients(n=40)was associated with an improvement in mental health-related quality of life(d = 0.70,  P<.001). These results indicate that despite the complex health needs of these underserved communities, telepsychology interventions may help offset the disparities in health service access in rural areas.
Thirty Years of Research on Met Receptor to Move a Biomarker from Bench to Bedside
Authors: Furlan Alessandro , Kherrouche Zoulika , Montagne Rémi , Copin Marie-Christine , Tulasne David 
Published: November 2014

Abstract
Met receptor tyrosine kinase was discovered in 1984 as an oncogene. Thirty years later, Met and its ligand hepatocyte growth factor/scatter factor are promising targets for the novel therapies developed to fight against cancers, with more than 240 clinical trials currently conducted. In this review, we offer to trace and highlight the most recent findings of the exemplary track record of research on Met receptor, which allowed moving this biomarker from bench to bedside. Indeed, three decades of basic research unravelled the structural basis of the ligand/receptor interaction and their complex downstream signaling network. During this period, animal models highlighted their crucial role in the development and homeostasis of epithelial organs. In parallel, involvement of Met in tumorigenesis was confirmed by the direct association of its deregulation to poor prognosis in numerous cancers. On the basis of these data, pharmaceutical companies developed many Met inhibitors, some of which are in phase III clinical trials. These impressive achievements should not detract from many questions that still remain, such as the precise Met signaling involvement in development or homeostasis of specific epithelial structures. In addition, the processes involving Met in resistance to current therapies or the appearance of resistances to Met-targeted therapies are far from being fully understood. Cancer Res; 74(23); 6737–44. ©2014 AACR.
Chromosomal assignment of oil radish resistance to Meloidogyne incognita and M. javanica using a set of disomic rapeseed-radish chromosome addition lines
Authors: Zhang Shaosong , Schliephake Edgar , Budahn Holger 
Published: November 2014

Root-knot nematodes cause severe damage to a great number of crops worldwide. The use of nematicides is restricted due to environmental and toxicological risks and control of the pest by crop rotation is difficult because root-knot nematodes have a very wide range of host plants. To verify the strategy of converting rapeseed from a tolerant host for Meloidogyne incognita and M. javanica to a resistant catch crop, a complete set of nine disomic rapeseed-radish chromosome addition lines (lines A to I) was tested for resistance against these Meloidogyne species. Thirty plants of each addition line and the rapeseed and radish parents as control were infected with 2500 second-stage juveniles per plant. The presence of the alien radish chromosome was confirmed by chromosome-specific microsatellite markers. After cultivation of the inoculated plants for 10 weeks in a climatic chamber the root systems were washed. The egg masses were stained with Cochenille Red and counted. The radish parent A24 was found to be resistant to M. incognita (2.4 egg masses (g root)−1) and M. javanica (0.4 egg masses (g root)−1) compared to 53.3 and 33.1 egg masses (g root)−1 for the susceptible rapeseed parent cv. Madora. The radish chromosome e was shown to be the carrier of radish root-knot nematode resistance with an average number of <1 egg mass (g root)−1 for M. incognita and M. javanica. The disomic addition lines B, C, D, G, H and I and the parental radish line A107 were classified as highly susceptible, whereas the addition lines A and F showed significantly reduced susceptibility for M. incognita but not for M. javanica. To our knowledge this is the first study on resistance effects of individual radish chromosomes in a rapeseed background against these root-knot nematodes.
Effects of selective β1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis
Authors: Calzavacca Paolo , Lankadeva Yugeesh R , Bailey Simon R , Bailey Michael , Bellomo Rinaldo , May Clive N 
Published: November 2014

Abstract
Introduction
Activation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.

Methods
Hyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis.

Results
Hyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6.

Conclusions
In sepsis, selective β1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect.
Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer
Authors: Cohen Helit , Ben-Hamo Rotem , Gidoni Moriah , Yitzhaki Ilana , Kozol Renana , Zilberberg Alona , Efroni Sol 
Published: November 2014

Abstract
Introduction
GATA binding protein 3 (GATA3) is a regulator of mammary luminal cell differentiation, and an estrogen receptor (ER) associated marker in breast cancer. Tumor suppressor functions of GATA3 have been demonstrated primarily in basal-like breast cancers. Here, we focused on its function in luminal breast cancer, where GATA3 is frequently mutated, and its levels are significantly elevated.

Methods
GATA3 target genes were identified in normal- and luminal cancer- mammary cells by ChIP-seq, followed by examination of the effects of GATA3 expressions and mutations on tumorigenesis-associated genes and processes. Additionally, mutations and expression data of luminal breast cancer patients from The Cancer Genome Atlas were analyzed to characterize genetic signatures associated with GATA3 mutations.

Results
We show that some GATA3 effects shift from tumor suppressing to tumor promoting during tumorigenesis, with deregulation of three genes, BCL2, DACH1, THSD4, representing major GATA3-controlled processes in cancer progression. In addition, we identify an altered activity of mutant GATA3, and distinct associated genetic signatures. These signatures depend on the functional domain mutated; and, for a specific subgroup, are shared with basal-like breast cancer patients, who are a clinical group with regard to considerations of mode of treatment.

Conclusions
The GATA3 dependent mechanisms may call for special considerations for proper prognosis and treatment of patients.