bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule imaging reveals the mechanism of Exo1 regulation by single-stranded DNA binding proteins
Authors: Myler Logan R. , Gallardo Ignacio F. , Zhou Yi , Gong Fade , Yang Soo-Hyun , Wold Marc S. , Miller Kyle M. , Paull Tanya T. , Finkelstein Ilya J. 
Published: February 2016

SignificanceExonuclease 1 (Exo1) is a conserved eukaryotic nuclease that participates in DNA repair and telomere maintenance. Here we use high-throughput single-molecule imaging to examine Exo1 activity on DNA and in the presence of single-stranded DNA binding proteins. We report that both human and yeast Exo1 are processive nucleases but are rapidly turned over by replication protein A (RPA). In the presence of RPA, Exo1 retains limited DNA-processing activity, albeit via a distributive binding mechanism. This rapid turnover by RPA can appear stimulatory or inhibitory in gel-based assays, clarifying conflicting results in the existing literature. RPA-depleted human cells show elevated Exo1 loading but reduced overall DNA resection, underscoring the many roles of RPA in regulating DNA resection in vivo.
Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice
Authors: Li Jun , Sung Cecilia Ying Ju , Lee Nikki , Ni Yueqiong , Pihlajamäki Jussi , Panagiotou Gianni , El-Nezami Hani 
Published: February 2016

SignificanceHepatocellular carcinoma is the second most deadly cancer type globally, requiring the development of alternative or complementary therapeutic and prophylactic methods. Here, when feeding a mouse model with a novel probiotic mixture 1 wk before the tumor inoculation, we observed a reduction of the tumor weight and size by 40% compared with the control. Our results revealed that the probiotics’ beneficial effect is closely related with the abundance of certain beneficial bacteria that produce antiinflammatory metabolites, which subsequently regulate the proinflammatory immune cell population via the crosstalk between gut and tumor. We believe that our study highlights the extraordinary potential of probiotics in extraintestine cancers and can be adapted to the study of other cancers.
How structural adaptability exists alongside HLA-A2 bias in the human αβ TCR repertoire
Authors: Blevins Sydney J. , Pierce Brian G. , Singh Nishant K. , Riley Timothy P. , Wang Yuan , Spear Timothy T. , Nishimura Michael I. , Weng Zhiping , Baker Brian M. 
Published: February 2016

SignificanceT-cell receptor (TCR) recognition of antigenic peptides presented by major histocompatibility complex (MHC) proteins defines specificity in cellular immunity. Evidence suggests that TCRs are intrinsically biased toward MHC proteins, yet how this bias coexists alongside the considerable structural variability that is necessary for TCRs to engage different ligands has been a longstanding puzzle. By examining structural and sequence data, we found evidence that human αβ TCRs have an inherent compatibility with structural and chemical properties of MHC proteins. This compatibility leads TCRs to an intrinsic MHC bias but does not compel the formation of particular modes of binding, providing a solution to how TCRs can be MHC-biased but still structurally adaptable.
Malignant Clear Cell Acanthoma: Report of a Rare Case of Clear Cell Acanthoma-Like Tumor With Malignant Features
Authors: Lin Chien-yio , Lee Li-yu , Kuo Tseng-tong 
Published: February 2016

Abstract:
An erythematous and moist tumor nodule on the left temple of a 92-year-old woman was biopsied and identified as a clear cell acanthoma (CCA)-like tumor with malignant cytology and high proliferation activity. This case is similar to 2 cases reported previously as atypical CCA. The authors believe that these tumors are malignant counterparts of CCA and propose to call them malignant CCA. The clinicopathologic features of the present case are described along with dermoscopic findings.
Parental Physical Proximity in End-of-Life Care in the PICU
Authors: Falkenburg Jeannette L. , Tibboel Dick , Ganzevoort Ruard R. , Gischler Saskia , Hagoort Jacobus , van Dijk Monique 
Published: February 2016

Objective:
Health professionals in PICUs support both child and parents when a child’s death is imminent. Parents long to stay connected to their dying child but the high-tech environment and treatment implications make it difficult to stay physically close. This study explores in what sense physical aspects of end-of-life care in the PICU influence the parent-child relationship.

Design:
Retrospective, qualitative interview study.

Setting:
Level 3 PICU in Erasmus Medical Center in the Netherlands.

Participants:
Thirty-six parents of 20 children who had died in this unit 5 years previously.

Measurements and Main Results:
Parents vividly remembered the damage done to the child’s physical appearance, an inevitable consequence of medical treatment. They felt frustrated and hurt when they could not hold their child. Yet they felt comforted if facilitated to be physically close to the dying child, like lying with the child in one bed, holding the child in the hour of death, and washing the child after death.

Conclusions:
End-of-life treatment in the PICU presents both a barrier and an opportunity for parents to stay physically connected to their child. Parents’ experiences suggest that aspects of physicality in medical settings deserve more attention. Better understanding of the significance of bodily aspects—other than pain and symptom management—improves end-of-life support and should be part of the humane approach to families.
Midcarpal and Scaphotrapeziotrapezoid Arthritis in Patients with Carpometacarpal Arthritis
Authors: Katzel Evan B. , Bielicka Dierde , Shakir Sameer , Fowler John , Buterbaugh Glenn A. , Imbriglia Joseph E. 
Published: February 2016

Background:
Carpometacarpal arthroplasty provides well-documented pain relief with preservation of thenar function in basal joint arthritis treatment. Nevertheless, some patients continue to have pain following surgery. The authors hypothesize that unrecognized midcarpal (capitolunate) arthritis is a contributor to persistent pain after carpometacarpal arthroplasty. The prevalence of midcarpal arthritis in patients with basal joint arthritis is unknown. This article establishes the radiographic prevalence of midcarpal arthritis in patients with carpometacarpal arthritis.

Methods:
Patients with basal joint arthritis were identified from a search using International Classification of Diseases, Ninth Revision code 716.94. Hand radiographs were reviewed and graded using the Eaton classification and Sodha classification for carpometacarpal arthritis. Scaphotrapeziotrapezoid arthritis and midcarpal arthritis were graded using the Sodha classification for arthritis as follows: grade 1, no or nearly no arthrosis; grade 2, definite arthrosis but not severe; and grade 3, severe arthrosis.

Results:
Eight hundred ninety-six radiographs were reviewed. The prevalence of scaphotrapeziotrapezoid arthritis in this population was 64 percent. The prevalence of midcarpal arthritis in this population was 23.5 percent. The prevalence of midcarpal arthritis in patients with radiologic evidence of carpometacarpal arthritis was 25.4 percent. The prevalence of severe midcarpal arthritis was 7 percent.

Conclusions:
The prevalence of midcarpal arthritis in patients with basal joint arthritis is 24 percent. The presence of two locations of arthritis may explain persistent hand and wrist pain in this population despite carpometacarpal arthroplasty. Clinically, these data will allow hand surgeons to better educate patients with basal joint arthritis regarding the possibility of incomplete pain relief following carpometacarpal arthroplasty.
Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C
Authors: Valcour Victor G. , Rubin Leah H. , Obasi Mary U. , Maki Pauline M. , Peters Marion G. , Levin Susanna , Crystal Howard A. , Young Mary A. , Mack Wendy J. , Cohen Mardge H. , Pierce Christopher B. , Adimora Adaora A. , Tien Phyllis C. ,   for the Women's Interagency HIV Study Protocol Team
Published: February 2016

Objective:
Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis.

Background:
Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation.

Design/Methods:
A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303).

Results:
We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency.

Conclusions:
Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.
Pharmacokinetics of Co-Formulated Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate After Switch From Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Healthy Subjects
Authors: Ramanathan Srini , Custodio Joseph M. , Wei Xuelian , Wang Hui , Fordyce Marshall , Dave Ami , Ling Kah Hiing J. , Szwarcberg Javier , Kearney Brian P. 
Published: February 2016

Background:
Elvitegravir (EVG), a HIV integrase inhibitor, is metabolized primarily by CYP3A, and secondarily by UGT1A1/3; Efavirenz (EFV), a HIV non-nucleoside reverse transcriptase inhibitor, is metabolized by Cytochrome P450 (CYP) 2B6 and induces CYP3A and uridine diphosphate glucuronosyltransferase (UGT) with residual effects post discontinuation because of long T1/2 (40–55 hours). This study evaluated the pharmacokinetics after switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF).

Methods:
Healthy subjects (n = 32 including n = 8 CYP2B6 poor metabolizers) received EVG/COBI/FTC/TDF (150/150/200/300 mg) on days 1–7, and after a washout, received EFV/FTC/TDF (600/200/300 mg) on days 15–28 and switched to EVG/COBI/FTC/TDF (150/150/200/300 mg) for 5 weeks (days 29–62). Pharmacokinetic assessments occurred on days 7, 28, 35, and 42; trough samples (Ctrough) were collected periodically until day 63. Safety was assessed throughout the study.

Results:
Twenty-nine subjects completed with 3 adverse events leading to discontinuation; no grade ≥3 adverse events were reported. Post-EFV/FTC/TDF, mean EVG area under concentration (AUCtau) was 37% and 29% lower and mean Ctrough ∼3- and ∼5-fold above IC95, respectively, on days 35 and 42, and 7–8-fold above IC95 by 5 weeks. COBI AUCtau returned to normal by day 42. EVG glucuronide, GS-9200, AUCtau was higher (46% and 32% on days 35 and 42, respectively) postswitch. CYP2B6 poor metabolizers displayed higher EFV AUCtau and Cmax (125% and 91%, respectively) versus non-poor metabolizers, and lower EVG and COBI exposures. EFV Ctrough was >IC90 (10 ng/mL) in all subjects postswitch. FTC and tenofovir (TFV) exposures were unaffected.

Conclusions:
After EFV/FTC/TDF to EVG/COBI/FTC/TDF switch, EVG and/or EFV exposures were in an active range. These findings support further evaluation of switching regimens in HIV-1 patients.
A study of how ICT capabilities can influence dynamic capabilities
Authors: Parida Vinit , Oghazi Pejvak , Cedergren Stefan 
Published: February 2016

Purpose– Prior studies have argued that small firms with dynamic capabilities can revise and reconfigure their internal resources to meet the uncertainties of their business environment. However, there is a lack of understanding of how they can develop such critical capabilities. The purpose of this paper is to propose that small firms can employ information and communication technology (ICT) capabilities as a facilitator for developing dynamic capabilities. Thus, the study builds on resource-based view (RBV) literature and information systems (IS) literature by examining the influence of ICT capabilities on the dynamic capabilities of small firms.Design/methodology/approach– Several hypotheses were tested by analysing the survey data from 291 small high-technology firms in Sweden.Findings– The results reveal that ICT capabilities influence dynamic capabilities of small firms. More specifically, the ICT use for internal efficiency positively influences adoptive capabilities, collaborative use of ICT positively influences networking capabilities, and ICT use for communications positively influences both adaptive and innovation capabilities. Consequently, the results suggest that the different components of ICT capabilities facilitate the development of the different organizational capabilities that together represent dynamic capabilities and thus, can contribute to a small firm’s competitive advantage.Practical implications– This study has few implications for the managers and CEO’s of small high-technology firms. First, by prioritizing ICT capabilities, small firms can benefit from the development of dynamic capabilities that will support them to meet the challenges of turbulent business environment. Second, because small firms usually lack internal resources (i.e. financial resources and competence), the study provides more specific direction on how they can strategically invest and build different components of ICT that will positively influence their adaptive, absorptive, innovative, and network capabilities.Originality/value– The study provides an alternative view of how ICT capabilities influence the performance of small firms, and outlines how such capabilities influence the development of dynamic capabilities. Therefore, the study in hand contributes to the RBV and IS literature by specifically linking the components of ICT capabilities to dynamic capabilities and its related sub-capabilities.
A multidimensional measure of managers’ contextual and task performance
Authors: Hosie Peter , Nankervis Alan 
Published: February 2016

Purpose– The purpose of this paper it to report the findings of an empirical study into managers’ job performance. A new measure was developed from the literature to test and establish the multidimensional structure of managers’ contextual and task performance.Design/methodology/approach– Field ratings by executives explicitly and simultaneously measured both managers’ contextual and task performance. A cross-sectional questionnaire was administered to a variety of public and third sector managers from a range of private, public and third sector occupations residing in (Western) Australia. A purposive sample yielded a response rate of 32 percent. Factor analysis was used to determine the items that constitute executives’ perceptions of managers’ performance using downward appraisal (i.e. by the person to whom a manager reports).Findings– The construct “managers’ job performance” was found to be multidimensional; consisting of four distinct contextual factors (Following, Persisting, Helping, Endorsing) and a further four distinct task factors (Delegating, Monitoring, Technical, Influencing).Originality/value– Performance appraisals of managers represent new items and factors that more accurately reflect the nature of the broader roles undertaken by managers, including transformative and ethical leadership. Findings from this study assist in establishing the structure for the subsequent appraisal of managers’ contextual and task performance. Future researchers could test the applicability and replicability of this new instrument in more diverse industry contexts using confirmatory statistical analysis.
Systemic T Cells and Monocyte Characteristics in Patients with Denture Stomatitis
Authors: Maciąg Joanna , Mikołajczyk Tomasz , Matusik Paweł , Nosalski Ryszard , Sagan Agnieszka , Maciąg Anna , Nowakowski Daniel , Wilk Grzegorz , Osmenda Grzegorz , Guzik Tomasz , Cześnikiewicz‐Guzik Marta 
Published: February 2016

AbstractPurposeChronic inflammatory disorders of the oral cavity, such as periodontitis, were recently linked to systemic immune activation. Since fungal oral infections have not yet been studied in this respect, the aim of our study is to determine whether the local inflammation caused by oral fungal infection of the palatal tissue (denture stomatitis—DS) is associated with the systemic inflammatory response. This question is becoming essential as the population ages.Materials and MethodsPeripheral blood of DS patients (n = 20) and control patients (n = 24) was assessed with flow cytometry to determine lymphocyte and monocyte profiles. Intracellular cytometric analysis was carried out to establish cytokine production by T cells. DS was diagnosed based on clinical symptoms of DS such as swelling and redness of oral mucosa, confirmed by microbiological swabs for fungal colonization with Candida species. The control group was recruited from denture users without clinical and microbiological signs of oral infections.ResultsPercentages of peripheral lymphocytes, T cells, monocytes, and their subpopulations were similar in both studied groups. The exception was median percentages of CD25+ T cell subsets, which were significantly lower in DS patients than in control subjects. This reduction was observed in both CD4 T cell subset (16.7% and 28.1%; p = 0.0006) and CD8 T cell subset (4.6% and 7.0%; p = 0.007)ConclusionsWhile DS and associated local fungal infection do not overtly affect activation of monocytes or lymphocytes, the number of CD 25+ T cells is significantly lower in the DS patients, possibly indicating limited potential for the infection clearance in denture‐using aging patients.
Comparative Study of Activities of a Diverse Set of Antimycobacterial Agents against Mycobacterium tuberculosis and Mycobacterium ulcerans
Authors: Scherr Nicole , Pluschke Gerd , Panda Manoranjan 
Published: February 2016

ABSTRACT

A library of compounds covering a broad chemical space was selected from a tuberculosis drug development program and was screened in a whole-cell assay against
Mycobacterium ulcerans
, the causative agent of the necrotizing skin disease Buruli ulcer. While a number of potent antitubercular agents were only weakly active or inactive against
M. ulcerans
, five compounds showed high activity (90% inhibitory concentration [IC
90
], ≤1 μM), making screening of focused antitubercular libraries a good starting point for lead generation against
M. ulcerans
.
Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro
Authors: Bax Hannelore I. , Bakker-Woudenberg Irma A. J. M. , ten Kate Marian T. , Verbon Annelies , de Steenwinkel Jurriaan E. M. 
Published: February 2016

ABSTRACT

The
in vitro
activities of clarithromycin and tigecycline alone and in combination against
Mycobacterium avium
were assessed. The activity of clarithromycin was time dependent, highly variable, and often resulted in clarithromycin resistance. Tigecycline showed concentration-dependent activity, and mycobacterial killing could only be achieved at high concentrations. Tigecycline enhanced clarithromycin activity against
M. avium
and prevented clarithromycin resistance. Whether there is clinical usefulness of tigecycline in the treatment of
M. avium
infections needs further study.
The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule
Authors: Mégroz Marianne , Kleifeld Oded , Wright Amy , Powell David , Harrison Paul , Adler Ben , Harper Marina , Boyce John D. 
Published: February 2016

ABSTRACT

The Gram-negative bacterium
Pasteurella multocida
is the causative agent of a number of economically important animal diseases, including avian fowl cholera. Numerous
P. multocida
virulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA-binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that a
P. multocida
hfq
mutant produces significantly less hyaluronic acid capsule during all growth phases and displays reduced
in vivo
fitness. Transcriptional and proteomic analyses of the
hfq
mutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of the
hfq
mutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in the
hfq
mutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression of
P. multocida
genes, including the regulation of key
P. multocida
virulence factors, capsule, LPS, and filamentous hemagglutinin.