bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of Polymeric Immunoglobulin Receptor and Neonatal Fc Receptor Expression in the Gut Mucosa of Immunodeficiency Virus‐Infected Rhesus Macaques
Authors: Wang Y. , Yang GB. 
Published: February 2016

AbstractPolymeric immunoglobulin receptors (pIgR) and neonatal Fc receptors (FcRn) are crucial immunoglobulin (Ig) receptors for the transcytosis of immunoglobulins, that is IgA, IgM and IgG, the levels of which in mucosal secretions were altered in both HIV‐ and SIV‐infected individuals. To gain an insight into the changes of pIgR and FcRn expression after immunodeficiency virus (SHIV/SIV) infection, real‐time RT‐PCR methods were established and the mRNA levels of pIgR and FcRn in normal and SHIV/SIV‐infected rhesus macaques were quantitatively examined. It was found that the levels of pIgR mRNA were within a range of 107 copies per million copies of GAPDH mRNA in the gut mucosa of rhesus macaques, which were up to 55 times higher than that in the oral mucosa, the highest among the non‐gut tissues examined. Levels of FcRn mRNA were generally lower than that of pIgR, and the levels of FcRn mRNA in the gut mucosa were also lower than that in most non‐gut tissues examined. Notably, the levels of pIgR mRNA in the duodenal mucosa were positively correlated with that of IL‐17A in normal rhesus macaques. Both pIgR and FcRn mRNA levels were significantly reduced in the duodenal mucosa during acute SHIV infection and in the jejunum and caecum during chronic SHIV/SIV infection. These data expanded our knowledge on the expression of pIgR and FcRn in the gastrointestinal tract of rhesus macaques and demonstrated altered expression of pIgR and FcRn in SHIV/SIV, and by extension HIV infections, which might have contributed to HIV/AIDS pathogenesis.
Personality traits, gender differences and symptoms of anhedonia: What does the Hospital Anxiety and Depression Scale (HADS) measure in nonclinical settings?
Authors: Langvik Eva , Hjemdal Odin , Nordahl Hans M. 
Published: February 2016

In healthy populations men report more depressive symptoms than women when depression is measured by the Hospital Anxiety and Depression Scale (HADS). This study aims to investigate the role of neuroticism and extroversion in symptom reporting by men and women and whether anhedonia can explain these reversed gender differences in depression observed when using HADS. HADS, Positive and Negative Affect Schedule (PANAS) and NEO Five Factor Inventory (NEO FFI) were administered twice to a sample of university students. Number of subjects at T1 was 372 and 160 at T2, measured two months apart. Men had a higher average score on depressive symptoms measured by HADS‐D compared to women (p = 0.029). Women scored higher than men on HADS‐A (p = 0.012), neuroticism (p < 0.001) and PANAS‐negative affect (p < 0.029). No significant gender differences were observed in extroversion and positive affect. Test‐retest stabilities on HADS‐A and HADS‐D were high. Neuroticism predicted HADS‐A at Time 2. Gender, extroversion, and neuroticism predicted HADS‐D at Time 2. The anhedonic content in HADS may be a plausible explanation of reversed gender differences in the HADS depression scale. HADS‐D represents a specific anhedonic subtype of depression where symptom reporting reflects dispositional tendencies related specifically to extroversion.
Exploring Communication Challenges Between Nurses and Mechanically Ventilated Patients in the Intensive Care Unit: A Structured Review
Authors: Dithole Kefalotse , Sibanda Sambulelwe , Moleki Mary M. , Thupayagale‐Tshweneagae Gloria 
Published: February 2016

ABSTRACTBackgroundMechanical ventilation is a necessary procedure for patients with a range of illnesses and conditions. Mechanical ventilation affects voice production, leaving patients unable to communicate their needs with nurses and family. The communication difficulty causes distress, frustration, and anger if not attended to.AimsThis structured review sought to identify communication challenges which exist between nurses and mechanically ventilated patients in intensive care units (ICU) and hence explore possible solutions to improve these communication challenges.MethodsA electronic search of MEDLINE, CINAHL, and PsycINFO was conducted to identify relevant literature on nurse–patient communication challenges in the ICU published between January 2005 and December 2014. Studies meeting the inclusion criteria were retrieved in full, reviewed, and study quality assessed.ResultsSix studies were identified for inclusion in the review. Analysis identified five core influences on communication in the ICU: patient's consciousness level, nature of nurse–patient interactions, communication methods, staff skills and perceptions, and the intensive care physical environment.Linking Evidence to ActionAn evidence‐based and multifactorial communication intervention encompassing staff skills development and training, development of relevant patient materials or devices and collaborations with relevant health professionals like speech and language therapists has the potential to improve nurse–patient communication in the ICU and hence improve patient outcomes.
The repair Schwann cell and its function in regenerating nerves
Authors: Jessen K. R. , Mirsky R. 
Published: February 2016

AbstractNerve injury triggers the conversion of myelin and non‐myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de‐differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury‐induced Schwann cell reprogramming involves down‐regulation of myelin genes combined with activation of a set of repair‐supportive features, including up‐regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair programme is controlled transcriptionally by mechanisms involving the transcription factor c‐Jun, which is rapidly up‐regulated in Schwann cells after injury. In the absence of c‐Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c‐Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non‐myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed.
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Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
Authors: Fernandez-Garcia Maria Dolores , Meertens Laurent , Chazal Maxime , Hafirassou Mohamed Lamine , Dejarnac Ophélie , Zamborlini Alessia , Despres Philippe , Sauvonnet Nathalie , Arenzana-Seisdedos Fernando , Jouvenet Nolwenn , Amara Ali 
Published: February 2016

ABSTRACT
The live attenuated yellow fever virus (YFV) vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation.

IMPORTANCE
The yellow fever virus (YFV) vaccine 17D is one of the safest and most effective live virus vaccines ever developed. The molecular determinants for virulence attenuation and immunogenicity of 17D are poorly understood. 17D was generated by serially passaging the virulent Asibi strain in vertebrate tissues. Here we examined the entry mechanisms engaged by YFV Asibi and the 17D vaccine. We found the two viruses use different entry pathways. We show that the mutations differentiating the Asibi envelope (E) protein from the 17D E protein, which arose during attenuation, are key determinants for the use of these distinct entry routes. Finally, we demonstrate that 17D binds and enters host cells more efficiently than Asibi. This results in a higher uptake of viral RNA into the cytoplasm and consequently a greater cytokine-mediated antiviral response. Overall, our data provide new insights into the biology of YFV infection and the mechanisms of viral attenuation.
The Staphylococcus aureus Methicillin Resistance Factor FmtA Is a
d
-Amino Esterase That Acts on Teichoic Acids
Authors: Rahman Muhammad M. , Hunter Howard N. , Prova Shamina , Verma Vidhu , Qamar Aneela , Golemi-Kotra Dasantila 
Published: February 2016

ABSTRACT

The methicillin resistance factor encoded by
fmtA
is a core member of the
Staphylococcus aureus
cell wall stimulon, but its function has remained elusive for the past two decades. First identified as a factor that affects methicillin resistance in
S. aureus
strains, FmtA was later shown to interact with teichoic acids and to localize to the cell division septum. We have made a breakthrough in understanding FmtA function. We show that FmtA hydrolyzes the ester bond between
d
-Ala and the backbone of teichoic acids, which are polyglycerol-phosphate or polyribitol-phosphate polymers found in the
S. aureus
cell envelope. FmtA contains two conserved motifs found in serine active-site penicillin-binding proteins (PBPs) and β-lactamases. The conserved SXXK motif was found to be important for the
d
-amino esterase activity of FmtA. Moreover, we show that deletion of
fmtA
(Δ
fmtA
) led to higher levels of
d
-Ala in teichoic acids, and this effect was reversed by complementation of Δ
fmtA
with
fmtA
. The positive charge on
d
-Ala partially masks the negative charge of the polyol-phosphate backbone of teichoic acids; hence, a change in the
d
-Ala content will result in modulation of their charge. Cell division, biofilm formation, autolysis, and colonization are among the many processes in
S. aureus
affected by the
d
-Ala content and overall charge of the cell surface teichoic acids. The esterase activity of FmtA and the regulation of
fmtA
suggest that FmtA functions as a modulator of teichoic acid charge, thus FmtA may be involved in
S. aureus
cell division, biofilm formation, autolysis, and colonization.

IMPORTANCE
Teichoic acids are involved in cell division, cell wall synthesis, biofilm formation, attachment of bacteria to artificial surfaces, and colonization. However, the function of teichoic acids is not fully understood. Modification by glycosylation and/or
d
-alanylation of the polyol-phosphate backbone of teichoic acids is important in the above cell processes. The intrinsic negative charge of teichoic acid backbone plays a role in the charge and/or pH of the bacterial surface, and
d
-alanylation represents a means through which bacteria modulate the charge or the pH of their surfaces. We discovered that FmtA removes
d
-Ala from teichoic acids. We propose FmtA may provide a temporal and spatial regulation of the bacterial cell surface charge in two ways, by removing the
d
-Ala from LTA to make it available to wall teichoic acid (WTA) in response to certain conditions and by removing it from WTA to allow the cell to reset its surface charge to a previous condition.
Registered nurse, healthcare support worker, medical staffing levels and mortality in English hospital trusts: a cross-sectional study
Authors: Griffiths Peter , Ball Jane , Murrells Trevor , Jones Simon , Rafferty Anne Marie 
Published: February 2016

ObjectivesTo examine associations between mortality and registered nurse (RN) staffing in English hospital trusts taking account of medical and healthcare support worker (HCSW) staffing.SettingSecondary care provided in acute hospital National Health Service (NHS) trusts in England.ParticipantsTwo data sets are examined: Administrative data from 137 NHS acute hospital trusts (staffing measured as beds per staff member). A cross-sectional survey of 2917 registered nurses in a subsample of 31 trusts (measured patients per ward nurse).Outcome measureRisk-adjusted mortality rates for adult patients (administrative data).ResultsFor medical admissions, higher mortality was associated with more occupied beds per RN (RR 1.22, 95% CI 1.04 to 1.43, p=0.02) and per doctor (RR 1.10, 95% CI 1.05 to 1.15, p <0.01) employed by the trust whereas, lower HCSW staffing was associated with lower mortality (RR 0.95, 95% CI 0.91 to 1.00, p=0.04). In multivariable models the relationship was statistically significant for doctors (RR 1.08, 95% CI 1.02 to 1.15, p=0.02) and HCSWs (RR 0.93, 95% CI 0.89 to 0.98, p<01) but not RNs (RR 1.14, 95% CI 0.95 to 1.38, p=0.17). Trusts with an average of ≤6 patients per RN in medical wards had a 20% lower mortality rate compared to trusts with >10 patients per nurse (RR 0.80, 95% CI 0.76 to 0.85, p<0.01). The relationship remained significant in the multivariable model (RR 0.89, 95% CI 0.83 to 0.95, p<0.01). Results for surgical wards/admissions followed a similar pattern but with fewer significant results.ConclusionsWard-based RN staffing is significantly associated with reduced mortality for medical patients. There is little evidence for beneficial associations with HCSW staffing. Higher doctor staffing levels is associated with reduced mortality. The estimated association between RN staffing and mortality changes when medical and HCSW staffing is considered and depending on whether ward or trust wide staffing levels are considered.
Statin Use and Survival with Early-Stage Hepatocellular Carcinoma
Authors: Jeon Christie Y. , Goodman Marc T. , Cook-Wiens Galen , Sundaram Vinay 
Published: February 2016

Abstract
Background: Limited clinical and epidemiologic data suggest that statins may improve the outcomes of hepatocellular carcinoma (HCC), which has poor prognosis.
Methods: We identified 1,036 stage I or II HCC patients, diagnosed between 2007 and 2009, through the linked Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims database. Of these, 363 patients were using statin either at the time of their HCC diagnosis or afterwards. We conducted multivariable Cox regression analysis to estimate the time-dependent effect of statin on survival. The analysis included age, sex, resection, transarterial chemoembolization, transplantation, cirrhosis, cardiovascular disease, diabetes, dyslipidemia, and hepatitis B and C.
Results: Over a median follow-up time of 21 months, 584 HCC patients died. Statin users had a longer median survival compared with nonusers: 23.9 versus 18.9 months (P = 0.047). However, after accounting for immortal time bias and confounding, statin use was not associated with survival (HR, 0.98; 95% confidence interval, 0.80–1.20). The associations did not vary by hepatitis C or intensity of statin use.
Conclusion: Statin treatment after HCC diagnosis was not associated with survival in elderly patients with stage I/II disease.
Impact: Our study of nationally representative elderly patients with stage I or II HCC in the United States shows that statin treatment does not improve survival with liver cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 686–92. ©2016 AACR.
A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors
Authors: Bacac Marina , Fauti Tanja , Sam Johannes , Colombetti Sara , Weinzierl Tina , Ouaret Djamila , Bodmer Walter , Lehmann Steffi , Hofer Thomas , Hosse Ralf J. , Moessner Ekkehard , Ast Oliver , Bruenker Peter , Grau-Richards Sandra , Schaller Teilo , Seidl Annette , Gerdes Christian , Perro Mario , Nicolini Valeria , Steinhoff Nathalie , Dudal Sherri , Neumann Sebastian , von Hirschheydt Thomas , Jaeger Christiane , Saro Jose , Karanikas Vaios , Klein Christian , Umaña Pablo 
Published: February 2016

Abstract
Purpose: CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB.
Experimental Design: CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells.
Results: Simultaneous binding of CEA TCB to tumor and T cells leads to formation of immunologic synapses, T-cell activation, secretion of cytotoxic granules, and tumor cell lysis. CEA TCB activity strongly correlates with CEA expression, with higher potency observed in highly CEA-expressing tumor cells and a threshold of approximately 10,000 CEA-binding sites/cell, which allows distinguishing between high- and low-CEA–expressing tumor and primary epithelial cells, respectively. Genetic factors do not affect CEA TCB activity confirming that CEA expression level is the strongest predictor of CEA TCB activity. In vivo, CEA TCB induces regression of CEA-expressing xenograft tumors with variable amounts of immune cell infiltrate, leads to increased frequency of activated T cells, and converts PD-L1 negative into PD-L1–positive tumors.
Conclusions: CEA TCB is a novel generation TCB displaying potent antitumor activity; it is efficacious in poorly infiltrated tumors where it increases T-cell infiltration and generates a highly inflamed tumor microenvironment. Clin Cancer Res; 22(13); 3286–97. ©2016 AACR.
Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy
Authors: Morita Rena , Hirohashi Yoshihiko , Torigoe Toshihiko , Ito-Inoda Satoko , Takahashi Akari , Mariya Tasuku , Asanuma Hiroko , Tamura Yasuaki , Tsukahara Tomohide , Kanaseki Takayuki , Kubo Terufumi , Kutomi Goro , Mizuguchi Toru , Terui Takeshi , Ishitani Kunihiko , Hashino Satoshi , Kondo Toru , Minagawa Nozomi , Takahashi Norihiko , Taketomi Akinobu , Todo Satoru , Asaka Masahiro , Sato Noriyuki 
Published: February 2016

Abstract
Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.
Experimental Design: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.
Results: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.
Conclusions: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298–309. ©2016 AACR.
Clinical and Molecular Characteristics of NF1-Mutant Lung Cancer
Authors: Redig Amanda J. , Capelletti Marzia , Dahlberg Suzanne E. , Sholl Lynette M. , Mach Stacy , Fontes Caitlin , Shi Yunling , Chalasani Poornima , Jänne Pasi A. 
Published: February 2016

Abstract
Purpose: NF1 is a tumor suppressor that negatively regulates Ras signaling. NF1 mutations occur in lung cancer, but their clinical significance is unknown. We evaluated clinical and molecular characteristics of NF1 mutant lung cancers with comparison to tumors with KRAS mutations.
Experimental Design: Between July 2013 and October 2014, 591 non–small cell lung cancer (NSCLC) tumors underwent targeted next-generation sequencing in a 275 gene panel that evaluates gene mutations and genomic rearrangements. NF1 and KRAS cohorts were identified, with subsequent clinical and genomic analysis.
Results: Among 591 patients, 60 had NF1 mutations (10%) and 141 (24%) had KRAS mutations. 15 NF1 mutations (25%) occurred with other oncogenic mutations [BRAF (2); ERBB2 (2); KRAS (9); HRAS (1); NRAS (1)]. There were 72 unique NF1 variants. NF1 tumor pathology was diverse, including both adenocarcinoma (36, 60%) and squamous cell carcinoma (10, 17%). In contrast, KRAS mutations occurred predominantly in adenocarcinoma (136, 96%). Both mutations were common in former/current smokers. Among NF1 tumors without concurrent oncogenic alterations, TP53 mutations/2-copy deletions occurred more often (33, 65%) than with KRAS mutation (46, 35%; P &lt; 0.001). No difference between cohorts was seen with other tumor suppressors.
Conclusions: NF1 mutations define a unique population of NSCLC. NF1 and KRAS mutations present in similar patient populations, but NF1 mutations occur more often with other oncogenic alterations and TP53 mutations. Therapeutic strategies targeting KRAS activation, including inhibitors of MAP kinase signaling, may warrant investigation in NF1 mutant tumors. Tumor-suppressor inactivation patterns may help further define novel treatment strategies. Clin Cancer Res; 22(13); 3148–56. ©2016 AACR.