bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol Consumption by workers in automobile repair shops of a slum of Kolkata: An assessment with AUDIT instrument
Authors: Dasgupta A , Ray S , Pal J , Biswas R , Ray D , Ghosal A 
Published: November 2013

Background National Household Survey of Drug Use in the India in its systematic effort to document the nationwide prevalence of drug use including alcohol consumption reported that almost 21% of the adult male Indian consume alcohol in a year. To find out prevalence, pattern and consequences of drinking and determine the relationship of alcohol use with demographic and socio-economic factors among auto-mobile repair workers. Materials and Methods A cross-sectional study was conducted among auto-mobile repair workers in the urban field practice area of All India Institute of Hygiene and Public Health, Kolkata. Results Prevalence of alcoholism in the community of automobile repair workers was found to be as high as 79%. More than 50% of the alcoholics belonged to the hazardous and dependent variety according to the WHO developed AUDIT instrument.53.01% of the alcoholics consumed foreign liquor predominantly and 87.95% bought them from licensed liquor shops. Mean age of initiation of drinking was 18.67 years. Taking loan OR (95% CI) 3.51(1.56-7.92), gambling OR (95% CI) 3.38(1.48-7.69) and clinical signs of alcoholism OR (95% CI) 5.52 (2.13 - 14.29) were significantly associated with chronic alcohol abuse. A multivariate logistic regression model was created for socio-economic variables which showed education AOR (95%CI) 4.65(1.34- 16.31) and total number of family members AOR (95%CI) 5.33(1.31-25.02) were significantly associated with drinking status (Nagelkerke R2 for this model is 0.2585). ConclusionThe prevalence of alcoholism is high in the automobile repair workers and therefore all efforts must be made to reduce, if not eliminate, alcohol consumption among the workers of auto-mobile service centres.DOI: http://dx.doi.org/10.3126/nje.v3i3.9188 Nepal Journal of Epidemiology 2013;3(3): 269-274
Patterns of recurrence after stereotactic radiosurgery for treatment of meningiomas
Authors: Kuhn Elizabeth N. , Taksler Glen B. , Dayton Orrin , Loganathan Amritraj G. , Vern-Gross Tamara Z. , Bourland J. Daniel , Laxton Adrian W. , Chan Michael D. , Tatter Stephen B. 
Published: December 2013

Object
The purpose of this study was to evaluate patterns of failure after stereotactic radiosurgery (SRS) for meningiomas and factors that may influence these outcomes.

Methods
Based on a retrospective chart review, 279 patients were treated with SRS for meningiomas between January 1999 and March 2011 at Wake Forest Baptist Health. Disease progression was determined using serial imaging, with a minimum follow-up of 6 months (median 34.2 months).

Results
The median margin dose was 12.0 Gy (range 8.8–20 Gy). Local control rates for WHO Grade I tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and 5 years, respectively. Tumors without pathological grading had local control rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local recurrences, 63.1% were classified as marginal (within 2 cm of treatment field). The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%, respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for Grade II/III tumors. Tumors without pathological grading had distant failure rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon analysis revealed that multifocal disease (p < 0.001) and high-grade histology (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence. Additionally, male sex was a significant predictor of distant recurrence (p = 0.04). Multivariate analysis also showed that doses greater than or equal to 12 Gy were associated with improved local control (p = 0.015).

Conclusions
In this patient series, 12 Gy was the minimum sufficient margin dose for the treatment of meningiomas. Male sex is a risk factor for distant failure, whereas high-grade histology and multifocal disease are risk factors for local failure.
Atypical meningiomas: is postoperative radiotherapy indicated?
Authors: Lee Kangmin D. , DePowell John J. , Air Ellen L. , Dwivedi Alok K. , Kendler Ady , McPherson Christopher M. 
Published: December 2013

Object
The role of postoperative radiation therapy after surgery for atypical meningiomas remains controversial. In this retrospective cohort study, the authors examine the recurrence rates for atypical meningiomas after resection (with or without adjuvant radiotherapy) and identify which factors were associated with recurrence.

Methods
Of 90 patients with atypical meningiomas who underwent surgery between 1999 and 2009, 71 (79%) underwent gross-total resection (GTR) and 19 (21%) underwent subtotal resection (STR); 31 patients received adjuvant radiotherapy. All tumors were pathology-confirmed WHO Grade II atypical meningiomas. Univariate and multivariate analyses were performed to identify factors associated with recurrence-free survival.

Results
Among 90 patients, 17 developed tumor recurrence (81% recurrence-free survival at 5 years). In the overall group, adjuvant radiotherapy reduced the recurrence rate to 9% from 19% at 5 years (p = 0.048). After STR, adjuvant radiotherapy significantly reduced recurrence from 91% to 20% (p = 0.0016). However, after GTR, adjuvant radiotherapy did not significantly reduce the recurrence rate (16.7% without radiation therapy vs 11.8% with radiation therapy) (p = 1.00). Five factors independently predictive of tumor recurrence included mitotic index, sheeting, necrosis, nonuse of radiation therapy, and STR. Further recursive partitioning analysis showed significant increases in risk for patients older than 55 years with mitoses and sheeting.

Conclusions
Adjuvant radiotherapy was effective at lowering recurrence rates in patients after STR but delivered no significant improvement in patients after GTR. Given that rates after GTR were similar with or without adjuvant radiotherapy, close observation without postoperative radiation therapy may be a viable option for these patients. Patients older than 55 years and those with mitoses noted during pathological examination had a significant risk of recurrence after GTR; for these patients, postoperative radiotherapy is recommended.
Iterative Development and Reliability of the OMERACT Hand Osteoarthritis MRI Scoring System
Authors: Haugen Ida K. , Østergaard Mikkel , Eshed Iris , McQueen Fiona M. , Bird Paul , Gandjbakhch Frederique , Foltz Violaine , Genant Harry , Peterfy Charles , Lillegraven Siri , Haavardsholm Espen A. , Bøyesen Pernille , Conaghan Philip G. 
Published: December 2013

Objective.To develop and test the interreader reliability of the OMERACT Hand Osteoarthritis Magnetic Resonance Scoring System (HOAMRIS) for assessment of structural and inflammatory hand OA features in the interphalangeal joints.Methods.The HOAMRIS was developed through an iterative process. Selection of features and their scaling was agreed upon through consensus by members of the OMERACT Magnetic Resonance Imaging (MRI) Task Force, using the Oslo Hand Osteoarthritis (OA) MRI Score system as a template. Two reliability exercises were performed, in which 6 and 4 readers participated, respectively. After the first exercise, an atlas was developed and used in the second exercise to facilitate reading. In each exercise, readers independently scored 8 MRI scans from the Oslo Hand OA cohort (coronal/axial short-tau inversion recovery and coronal/axial/sagittal T1-weighted fat-suppressed pre-/post-Gadolinium images). Interreader reliability was assessed by intraclass correlation coefficients (ICC), percentage exact and close agreement (PEA/PCA).Results.The preliminary OMERACT HOAMRIS included assessment of synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML), of which all were scored on a 0–3 scale for normal, mild, moderate, and severe (increments of 0.5 for synovitis, erosive damage, and BML). In the first exercise, most features showed good to very good ICC values (0.64–0.94), except synovitis (0.34). In the second exercise using the atlas, the ICC values were > 0.74 for all MRI features, and the PEA/PCA values were higher than in the first exercise.Conclusion.A preliminary HOAMRIS with good to very good interreader reliability was developed. Longitudinal studies are needed to assess its sensitivity to change.
Immunotherapy with TCR-Redirected T Cells: Comparison of TCR-Transduced and TCR-Engineered Hematopoietic Stem Cell–Derived T Cells
Authors: Stärck Lilian , Popp Katja , Pircher Hanspeter , Uckert Wolfgang 
Published: November 2013

Abstract
Redirecting Ag specificity by transfer of TCR genes into PBLs is an attractive method to generate large numbers of cytotoxic T cells for immunotherapy of cancer and viral diseases. However, transferred TCR chains can pair with endogenous TCR chains, resulting in the formation of mispaired TCR dimers and decreased or unspecific reactivity. TCR gene transfer into hematopoietic stem cells (HSCs) is an alternative to create T cells with desired Ag specificity, because in this case expression of endogenous TCR chains is then less likely owing to allelic exclusion. We generated TCR-transduced T cells from peripheral T cells using the lymphocytic choriomeningitis virus–specific P14 TCR. After transfer of the P14 TCR genes into HSCs and subsequent reconstitution of irradiated mice, TCR-engineered HSC-derived T cells were produced. We then compared the Ag-specific T cell populations with P14 TCR-transgenic T cells for their therapeutic efficiency in three in vivo models. In this study, we demonstrate that TCR-transduced T cells and TCR-engineered HSC-derived T cells are comparable in controlling lymphocytic choriomeningitis virus infection in mice and suppress growth of B16 tumor cells expressing the cognate Ag in a comparable manner.
MyD88 Signaling Regulates Both Host Defense and Immunopathogenesis during Pneumocystis Infection
Authors: Bello-Irizarry Sheila N. , Wang Jing , Johnston Carl J. , Gigliotti Francis , Wright Terry W. 
Published: November 2013

Abstract
The immune response protects against Pneumocystis infection but is also a key component of Pneumocystis pneumonia (PcP)–related immunopathogenesis. Signaling through myeloid differentiation factor 88 (MyD88) is critical for activation of immune pathways downstream of TLRs and IL-1R. To determine whether MyD88 regulates normal host defense against Pneumocystis, nonimmunosuppressed wild-type (WT) and MyD88-deficient mice were infected. MyD88−/− mice had higher early Pneumocystis burdens than did WT mice but mounted an effective adaptive immune response and cleared Pneumocystis similarly to WT. However, MyD88−/− mice displayed a more intense and prolonged pulmonary immune response than did WT mice. To determine the role of MyD88 in the development of PcP-related immunopathogenesis, WT and MyD88−/− mice were rendered susceptible to PcP by depletion of CD4+ T cells. At 4 wk postinfection, CD4-depleted WT and MyD88−/− mice harbored similar organism burdens, but MyD88−/− mice were protected from the PcP-related respiratory impairment observed in WT mice. Improved pulmonary physiology in MyD88−/− mice correlated with lower lung CCL2 levels and reduced cell recruitment. However, by 5 wk postinfection, the overall health of MyD88−/− mice began to deteriorate rapidly relative to WT, with accelerated weight loss, impaired lung function, and exacerbated alveolar inflammation. This physiological decline of MyD88−/− mice was associated with increased TNF-α and IFN-γ in the lung, and by the inability to control Pneumocystis burden. Thus, MyD88 is not required for resistance to Pneumocystis infection, but limits the adaptive immune response in immunocompetent mice. In the setting of active PcP, MyD88 signaling contributes to both immunopathogenesis and control of fungal burden.
Two Separate Defects Affecting True Naive or Virtual Memory T Cell Precursors Combine To Reduce Naive T Cell Responses with Aging
Authors: Renkema Kristin R. , Li Gang , Wu Angela , Smithey Megan J. , Nikolich-Žugich Janko 
Published: November 2013

AbstractNaive T cell responses are eroded with aging. We and others have recently shown that unimmunized old mice lose ≥70% of Ag-specific CD8 T cell precursors and that many of the remaining precursors acquire a virtual (central) memory (VM; CD44hiCD62Lhi) phenotype. In this study, we demonstrate that unimmunized TCR transgenic (TCRTg) mice also undergo massive VM conversion with age, exhibiting rapid effector function upon both TCR and cytokine triggering. Age-related VM conversion in TCRTg mice directly depended on replacement of the original TCRTg specificity by endogenous TCRα rearrangements, indicating that TCR signals must be critical in VM conversion. Importantly, we found that VM conversion had adverse functional effects in both old wild-type and old TCRTg mice; that is, old VM, but not old true naive, T cells exhibited blunted TCR-mediated, but not IL-15–mediated, proliferation. This selective proliferative senescence correlated with increased apoptosis in old VM cells in response to peptide, but decreased apoptosis in response to homeostatic cytokines IL-7 and IL-15. Our results identify TCR as the key factor in differential maintenance and function of Ag-specific precursors in unimmunized mice with aging, and they demonstrate that two separate age-related defects—drastic reduction in true naive T cell precursors and impaired proliferative capacity of their VM cousins—combine to reduce naive T cell responses with aging.
CD8+ T Cell–Independent Tumor Regression Induced by Fc-OX40L and Therapeutic Vaccination in a Mouse Model of Glioma
Authors: Murphy Katherine A. , Erickson Jami R. , Johnson Charles S. , Seiler Charles E. , Bedi Jessica , Hu Peisheng , Pluhar G. Elizabeth , Epstein Alan L. , Ohlfest John R. 
Published: November 2013

Abstract
Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Although some promising advances have been made, the immune response stimulated as a result of immunotherapeutic protocols has been inefficient at complete tumor elimination, primarily due to our lack of understanding of the necessary effector functions of the immune system. We previously demonstrated that a tumor lysate vaccine/Fc-OX40L therapy is capable of inducing enhanced survival and tumor elimination in the GL261 mouse glioma model. The following experiments were performed to determine the mechanism(s) of action of this therapy that elicits a potent antitumor immune response. The evidence subsequently outlined indicates a CD8+ T cell–independent and CD4+ T cell–, NK cell–, and B cell–dependent means of prolonged survival. CD8+ T cell–independent tumor clearance is surprising considering the current focus of many cancer immunotherapy protocols. These results provide evidence for CD8+ T cell–independent means of antitumor response and should lead to additional examination of the potential manipulation of this mechanism for future treatment strategies.
Neutralization of Plasmodium falciparum Merozoites by Antibodies against PfRH5
Authors: Douglas Alexander D. , Williams Andrew R. , Knuepfer Ellen , Illingworth Joseph J. , Furze Julie M. , Crosnier Cécile , Choudhary Prateek , Bustamante Leyla Y. , Zakutansky Sara E. , Awuah Dennis K. , Alanine Daniel G. W. , Theron Michel , Worth Andrew , Shimkets Richard , Rayner Julian C. , Holder Anthony A. , Wright Gavin J. , Draper Simon J. 
Published: November 2013

Abstract
There is intense interest in induction and characterization of strain-transcending neutralizing Ab against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly neutralizing Abs, but there is little information regarding the functional mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine-induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to erythrocytes and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 mAbs, we provide evidence of the following: 1) the ability to block the PfRH5–basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity; 2) neutralizing mAbs bind spatially related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence; 3) a brief exposure window of PfRH5 is likely to necessitate rapid binding of Ab to neutralize parasites; and 4) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly neutralizing anti-malaria Abs and further encourage anti-PfRH5–based malaria prevention efforts.
TGF-β Promotes Immune Responses in the Presence of Mesenchymal Stem Cells
Authors: Xu Chunliang , Yu Pengfei , Han Xiaoyan , Du Liming , Gan Jianhe , Wang Ying , Shi Yufang 
Published: November 2013

AbstractMesenchymal stem cells (MSCs) possess potent immunosuppression capacity and could exert strong therapeutic effects in many diseases, especially inflammatory disorders, in animal models and clinical settings. Although inflammatory cytokines are critical in inducing the immune modulatory properties of MSCs, detailed molecular mechanisms are yet to be fully understood. TGF-β is a well-known anti-inflammatory cytokine and exists in various inflammatory processes; therefore, we investigated whether it could synergize with MSCs in suppressing immune responses. To our surprise, we found that TGF-β actually reversed the immunosuppressive effect of MSCs on anti-CD3 activated splenocytes. Using TGF-β unresponsive MSCs, we demonstrated that the TGF-β directly acted on MSCs. Furthermore, we showed that the effect of TGF-β is exerted through inhibiting inflammatory cytokines induced inducible NO synthase (iNOS) expression in a SMAD3-dependent manner. Interestingly, we found that TGF-β produced by MSCs could act in an autocrine manner to reduce inflammatory cytokine-induced inducible NO synthase expression by MSCs themselves. Therefore, our study revealed a previously unrecognized property of TGF-β in promoting immune responses in the presence of MSCs.
Helicobacter pylori Cytotoxin-Associated Gene A Impairs Human Dendritic Cell Maturation and Function through IL-10–Mediated Activation of STAT3
Authors: Kaebisch Romy , Mejías-Luque Raquel , Prinz Christian , Gerhard Markus 
Published: November 2013

Abstract
Helicobacter pylori infection induces chronic gastric inflammation that can progress to cancer. In this process, the virulence factor cytotoxin-associated gene A (CagA) plays a central role by directly altering epithelial cell signaling and inducing a strong Th1 immune response, which contributes to carcinogenesis. It is still barely understood how the bacterium evades clearance despite this solid immune response and persists lifelong. Dendritic cells (DCs) play a major role in determining the adaptive immune response toward H. pylori, and high levels of regulatory T cells have been detected infiltrating the gastric mucosa of H. pylori–infected patients, which contribute to bacterial persistence. Although murine studies indicate that H. pylori induces tolerization of DCs and impairs DC maturation, the virulence determinants involved are still controversial. Moreover, the signaling cascades engaged in human DC tolerization upon H. pylori infection remain unknown. In the current study, we analyzed the effect of H. pylori infection on human DC maturation and function, focusing on the virulence factors implicated and signaling pathways involved. Our results reveal that CagA is crucial for DC tolerization by modulating IL-10 secretion and, in turn, STAT3 phosphorylation, favoring a regulatory T cell immune response. Our findings help to unravel the paradox why CagA-positive strains, although eliciting a stronger inflammatory response, have overcome evolutionary pressure and persisted in their human host.
Human Dendritic Cells Derived From Embryonic Stem Cells Stably Modified With CD1d Efficiently Stimulate Antitumor Invariant Natural Killer T Cell Response
Authors: Zeng Jieming , Wang Shu 
Published: November 2013

Abstract

Invariant natural killer T (iNKT) cells are a unique lymphocyte subpopulation that mediates antitumor activities upon activation. A current strategy to harness iNKT cells for cancer treatment is endogenous iNKT cell activation using patient-derived dendritic cells (DCs). However, the limited number and functional defects of patient DCs are still the major challenges for this therapeutic approach. In this study, we investigated whether human embryonic stem cells (hESCs) with an ectopically expressed CD1d gene could be exploited to address this issue. Using a lentivector carrying an optimized expression cassette, we generated stably modified hESC lines that consistently overexpressed CD1d. These modified hESC lines were able to differentiate into DCs as efficiently as the parental line. Most importantly, more than 50% of such derived DCs were CD1d+. These CD1d-overexpressing DCs were more efficient in inducing iNKT cell response than those without modification, and their ability was comparable to that of DCs generated from monocytes of healthy donors. The iNKT cells expanded by the CD1d-overexpressing DCs were functional, as demonstrated by their ability to lyse iNKT cell-sensitive glioma cells. Therefore, hESCs stably modified with the CD1d gene may serve as a convenient, unlimited, and competent DC source for iNKT cell-based cancer immunotherapy.
Generation of Functional Insulin-Producing Cells From Mouse Embryonic Stem Cells Through 804G Cell-Derived Extracellular Matrix and Protein Transduction of Transcription Factors
Authors: Kaitsuka Taku , Noguchi Hirofumi , Shiraki Nobuaki , Kubo Takuya , Wei Fan-Yan , Hakim Farzana , Kume Shoen , Tomizawa Kazuhito 
Published: November 2013

Abstract

Embryonic stem (ES) and induced pluripotent stem (iPS) cells have potential applications to regenerative medicine for diabetes; however, a useful and safe way to generate pancreatic β cells has not been developed. In this study, we tried to establish an effective method of differentiation through the protein transduction of three transcription factors (Pdx1, NeuroD, and MafA) important to pancreatic β cell development. The method poses no risk of unexpected genetic modifications in target cells. Transduction of the three proteins induced the differentiation of mouse ES and mouse iPS cells into insulin-producing cells. Furthermore, a laminin-5-rich extracellular matrix efficiently induced differentiation under feeder-free conditions. Cell differentiation was confirmed with the expression of the insulin 1 gene in addition to marker genes in pancreatic β cells, the differentiated cells secreted glucose-responsive C-peptide, and their transplantation restored normoglycemia in diabetic mice. Moreover, Pdx1 protein transduction had facilitative effects on differentiation into pancreatic endocrine progenitors from human iPS cells. These results suggest the direct delivery of recombinant proteins and treatment with laminin-5-rich extracellular matrix to be useful for the generation of insulin-producing cells.