bluuebunny/crossref_metadata_2025_split huggingface dataset:
DC-LAMP
+
Dendritic Cells Are Recruited to Gastric Lymphoid Follicles in Helicobacter pylori-Infected Individuals
Authors: Hansson Malin , Sundquist Malin , Hering Susanne , Lundin B. Samuel , Hermansson Michael , Quiding-Järbrink Marianne 
Published: July 2013

ABSTRACT

Infection with
Helicobacter pylori
is associated with development of ulcer disease and gastrointestinal adenocarcinoma. The infection leads to a large infiltration of immune cells and the formation of organized lymphoid follicles in the human gastric mucosa. Still, the immune system fails to eradicate the bacteria, and the substantial regulatory T cell (Treg) response elicited is probably a major factor permitting bacterial persistence. Dendritic cells (DCs) are professional antigen-presenting cells that can activate naive T cells, and maturation of DCs is crucial for the initiation of primary immune responses. The aim of this study was to investigate the presence and localization of mature human DCs in
H. pylori
-infected gastric mucosa. Gastric antral biopsy specimens were collected from patients with
H. pylori
-associated gastritis and healthy volunteers, and antrum tissue was collected from patients undergoing gastric resection. Immunohistochemistry and flow cytometry showed that DCs expressing the maturation marker dendritic cell lysosome-associated membrane glycoprotein (DC-LAMP; CD208) are enriched in the
H. pylori
-infected gastric mucosa and that these DCs are specifically localized within or close to lymphoid follicles. Gastric DC-LAMP-positive (DC-LAMP
+
) DCs express CD11c and high levels of HLA-DR but little CD80, CD83, and CD86. Furthermore, immunofluorescence analyses demonstrated that DC-LAMP
+
DCs are in the same location as FoxP3-positive putative Tregs in the follicles. In conclusion, we show that DC-LAMP
+
DCs with low costimulatory capacity accumulate in the lymphoid follicles in human
H. pylori
-infected gastric tissue, and our results suggest that Treg-DC interactions may promote chronic infection by rendering gastric DCs tolerogenic.
The Mucin Muc2 Limits Pathogen Burdens and Epithelial Barrier Dysfunction during Salmonella enterica Serovar Typhimurium Colitis
Authors: Zarepour Maryam , Bhullar Kirandeep , Montero Marinieve , Ma Caixia , Huang Tina , Velcich Anna , Xia Lijun , Vallance Bruce A. 
Published: July 2013

ABSTRACTSalmonella entericaserovar Typhimurium is a model organism used to explore the virulence strategies underlyingSalmonellapathogenesis. Although intestinal mucus is the first line of defense in the intestine, its role in protection againstSalmonellais still unclear. The intestinal mucus layer is composed primarily of the Muc2 mucin, a heavily O-glycosylated glycoprotein. The core 3-derived O-glycans of Muc2 are synthesized by core 3 β1,3-N-acetylglucosaminyltransferase (C3GnT). Mice lacking these glycans still produce Muc2 but display a thinner intestinal mucus barrier. We began our investigations by comparingSalmonella-induced colitis and mucus dynamics inMuc2-deficient (Muc2−/−) mice,C3GnT−/−mice, and wild-type C57BL/6 (WT) mice.Salmonellainfection led to increases in luminal Muc2 secretion in WT andC3GnT−/−mice. WhenMuc2−/−mice were infected withSalmonella, they showed dramatic susceptibility to infection, carrying significantly higher cecal and liver pathogen burdens, and developing significantly higher barrier disruption and higher mortality rates, than WT mice. We found that the exaggerated barrier disruption in infectedMuc2−/−mice wasinvAdependent. We also tested the susceptibility ofC3GnT−/−mice and found that they carried pathogen burdens similar to those of WT mice but developed exaggerated barrier disruption. Moreover, we found thatMuc2−/−mice were impaired in intestinal alkaline phosphatase (IAP) expression and lipopolysaccharide (LPS) detoxification activity in their ceca, potentially explaining their high mortality rates during infection. Our data suggest that the intestinal mucus layer (Muc2) and core 3 O-glycosylation play critical roles in controllingSalmonellaintestinal burdens and intestinal epithelial barrier function, respectively.
The effectiveness of schemes that refine referrals between primary and secondary care—the UK experience with glaucoma referrals: the Health Innovation & Education Cluster (HIEC) Glaucoma Pathways Project
Authors: Ratnarajan Gokulan , Newsom Wendy , Vernon Stephen A , Fenerty Cecilia , Henson David , Spencer Fiona , Wang Yanfang , Harper Robert , McNaught Andrew , Collins Lisa , Parker Mike , Lawrenson John , Hudson Robyn , Khaw Peng Tee , Wormald Richard , Garway-Heath David , Bourne Rupert 
Published: July 2013

ObjectivesA comparison of glaucoma referral refinement schemes (GRRS) in the UK during a time period of considerable change in national policy and guidance.DesignRetrospective multisite review.SettingThe outcomes of clinical examinations by optometrists with a specialist interest in glaucoma (OSIs) were compared with optometrists with no specialist interest in glaucoma (non-OSIs). Data from Huntingdon and Nottingham assessed non-OSI findings, while Manchester and Gloucestershire reviewed OSI findings.Participants1086 patients. 434 patients were from Huntingdon, 179 from Manchester, 204 from Gloucestershire and 269 from Nottingham.ResultsThe first-visit discharge rate (FVDR) for all time periods for OSIs was 14.1% compared with 36.1% from non-OSIs (difference 22%, CI 16.9% to 26.7%; p<0.001). The FVDR increased after the April 2009 National Institute for Health and Clinical Excellence (NICE) glaucoma guidelines compared with pre-NICE, which was particularly evident when pre-NICE was compared with the current practice time period (OSIs 6.2–17.2%, difference 11%, CI −24.7% to 4.3%; p=0.18, non-OSIs 29.2–43.9%, difference 14.7%, CI −27.8% to −0.30%; p=0.03). Elevated intraocular pressure (IOP) was the commonest reason for referral for OSIs and non-OSIs, 28.7% and 36.1%, respectively, of total referrals. The proportion of referrals for elevated IOP increased from 10.9% pre-NICE to 28.0% post-NICE for OSIs, and from 19% to 45.1% for non-OSIs.ConclusionsIn terms of ‘demand management’, OSIs can reduce FVDR of patients reviewed in secondary care; however, in terms of ‘patient safety’ this study also shows that overemphasis on IOP as a criterion for referral is having an adverse effect on both the non-OSIs and indeed the OSIs ability to detect glaucomatous optic nerve features. It is recommended that referral letters from non-OSIs be stratified for risk, directing high-risk patients straight to secondary care, and low-risk patients to OSIs.
Methods used to conduct and report Bayesian mixed treatment comparisons published in the medical literature: a systematic review
Authors: Sobieraj Diana M , Cappelleri Joseph C , Baker William L , Phung Olivia J , White C Michael , Coleman Craig I 
Published: July 2013

ObjectivesTo identify published closed-loop Bayesian mixed treatment comparisons (MTCs) and to summarise characteristics regarding their conduct and reporting.DesignSystematic review.MethodsWe searched multiple bibliographic databases (January 2006–31 July 2011) for full-text, English language publications of Bayesian MTCs comparing the effectiveness or safety of ≥3 interventions based on randomised controlled trials and having at least one closed loop. Methodological and reporting characteristics of MTCs were extracted in duplicate and summarised descriptively.ResultsWe identified 34 Bayesian MTCs spanning 13 clinical areas. Publication of MTCs increased over the 5-year period; with 76.5% published during or after 2009. MTCs included a mean (±SD) of 35.9±30.1 trials (n=33 459±71 233 participants) and 8.5±4.3 interventions (85.7% pharmacological). Non-informative and informative prior distributions were reported to be used in 44.1% and 8.8% of MTCs, respectively, with the remainder failing to specify the prior used. A random-effects model was used to analyse the networks of trials in 58.5% of MTCs, all using WinBUGS; however, code was infrequently provided (20.6%). More than two-thirds of MTCs (76.5%) also conducted traditional meta-analysis. Methods used to evaluate convergence, heterogeneity and inconsistency were infrequently reported, but from those providing detail, methods appeared varied. MTCs most often used a binary effect measure (85.3%) and ranking of interventions based on probability was common (61.8%), although rarely displayed in a figure (8.8% of MTCs). MTCs were published in 24 different journals with a mean impact factor of 9.20±8.71. While 70.8% of journals imposed limits on word counts and 45.8% limits on the number of tables/figures, online supplements/appendices were allowed in 79.2% of journals. Publication of closed-loop Bayesian MTCs is increasing in frequency, but details regarding their methodology are often poorly described. Efforts in clarifying the appropriate methods and reporting of Bayesian MTCs should be of priority.
Introduction effects of the Australian plain packaging policy on adult smokers: a cross-sectional study
Authors: Wakefield Melanie A , Hayes Linda , Durkin Sarah , Borland Ron 
Published: July 2013

ObjectiveTo determine whether smokers smoking from packs required under Australia's plain packaging law had different smoking beliefs and quitting thoughts, compared with those still smoking from branded packs.DesignCross-sectional survey during the roll-out phase of the law, analysed by timing of survey.SettingAustralian state of Victoria, November 2012.Participants536 cigarette smokers with a usual brand, of whom 72.3% were smoking from a plain pack and 27.7% were smoking from a branded pack.Primary outcome measuresPerceived quality and satisfaction of cigarettes compared with 1 year ago, frequency of thoughts of smoking harm, perceived exaggeration of harms, frequency of thoughts of quitting, quitting priority in life, intention to quit, approval of large graphic health warnings and plain packaging.ResultsCompared with branded pack smokers, those smoking from plain packs perceived their cigarettes to be lower in quality (adjusted OR (AdjOR)=1.66, p=0.045), tended to perceive their cigarettes as less satisfying than a year ago (AdjOR=1.70,p=0.052), were more likely to have thought about quitting at least once a day in the past week (AdjOR=1.81, p=0.013) and to rate quitting as a higher priority in their lives (F=13.11, df=1, p<0.001). Plain pack smokers were more likely to support the policy than branded pack smokers (AdjOR=1.51, p=0.049). Branded and plain pack smokers did not differ on measures of less immediate smoking intentions, frequency of thoughts about harms or perceived exaggeration of harms. Appeal outcomes, but not other outcomes, were sensitive to the extent of roll-out, with responses from branded pack smokers approaching those of plain pack smokers, once 80% of survey respondents were smoking from plain packs 1–2 weeks before the December implementation date.ConclusionsThe early indication is that plain packaging is associated with lower smoking appeal, more support for the policy and more urgency to quit among adult smokers.
Detection of fatty acids in the lateral extent of the cadaver decomposition island
Authors: Larizza Melina , Forbes Shari L. 
Published: July 2013

Abstract
Identifying biomarkers of decomposition may prove to be an important area of environmental and criminal forensics research. Biomarkers released during the decomposition process can be detected in soil as a means of confirming the presence of a decomposition site in the case of relocated or scavenged remains. This study was conducted to characterize the fatty acid profile in soil containing decomposition fluid and to determine the lateral extent of fatty acid release in the cadaver decomposition island (CDI). Owing to practical and ethical restrictions, the study utilized pig carcasses as human analogues to investigate postmortem decomposition on a soil surface. Soil samples were collected from directly beneath the carcasses and at increasing distances from the carcasses within the CDI. Fatty acids were extracted with chloroform, derivatized with a silylating agent and analysed using gas chromatography–mass spectrometry (GC-MS). Saturated and unsaturated fatty acids were detected including myristic (C14:0), palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0) and oleic (C18:1) acids. Fatty acids were detected up to 50 cm in the lateral extent of the CDI at significantly higher levels in decomposition soil than in the control soil. The results indicate that fatty acid analysis of decomposition soil could be used to confirm the location of a decomposition site.
The long Pleistocene record from the Pego-Oliva marshland (Alicante-Valencia, Spain)
Authors: Torres Trinidad , Ortiz José E. , Martín-Sánchez Domingo , Arribas Isabel , Moreno Laura , Ballesteros Bruno , Blázquez Ana , Domínguez José Antonio , Rodríguez Estrella Tomás 
Published: July 2013

Abstract
Seven borehole cores were analysed to reconstruct the Pleistocene evolution of the Pego-Oliva Basin (Mediterranean coast, Iberian Peninsula). A total of 295 samples were recovered for amino acid racemization (AAR) dating, and 77 samples for sedimentological, palaeontological and biomarker determination, with two objectives: (1) to establish a chronological framework (especially for Middle Pleistocene); and (2) to obtain data on the palaeoenvironment.

AAR proved that the record covers approximately 650 ka in which no important hiatuses occurred, although minor ones cannot be discarded. AAR provided valuable information on differential subsidence rates, and Marine Isotope Stages (MISs) 15–1 were identified.

Litho- and biofacies allowed the identification of distinct palaeoenvironments through time, with the constant presence of a marsh/lagoonal environment with brackish or saline water with continental or marine influence. Remains of marine molluscs allowed the determination of periods of highstand sea level. Biomarkers indicated a constant input from terrestrial plants, and allowed definitions of periods with variable water mass and environmental moisture. As in other Mediterranean littoral areas, facies with a marine influence occurred mainly during odd MISs, indicating periods of highstand sea level. In contrast, alluvial-fan progradation and continental brackish wetlands developed during even MISs.
Sedimentology, ichnology, ecology and anthropogenic modification of muddy tidal flats in a cold-temperate environment: Chignecto Bay, Canada
Authors: Dashtgard Shahin E. , Pearson Nadine J. , Gingras Murray K. 
Published: July 2013

Abstract
In Chignecto Bay, upper Bay of Fundy, Canada, the muddy tidal flats exhibit distinctive sedimentological and ichnological characteristics indicative of winter conditions and the development of ice. From late spring to autumn (May–October: mean temperature +13.6 °C), the mud flats sustain a high infaunal biomass and sediment deposition is dominated by tidal processes. Neap–spring tidal rhythmites, fluid-mud deposition and high levels of bioturbation are all characteristic of summer deposits. During the winter, temperatures remain below zero (December–March: mean temperature −6.3 °C), and ice forms in the bay and periodically on the mud flats. Ice rafts and blocks are common on the tidal-flat surface, and these blocks deform the muddy sediment, cut deep scours and deposit allochthonous sediment (including gravel) across the flats. Intermittent storms in the autumn and winter also contribute to sediment scouring and erosion. Annual die-offs of infauna are reflected by reduced bioturbation in winter deposits. Each spring, renewed larval recruitment and opportunistic colonization results in increasing levels of bioturbation, and the trace suite is dominated by a low-diversity assemblage of diminutive, vertical burrows. The summer–winter cyclicity in infaunal colonization manifests, ichnologically, as a distinctive bioturbated–non-bioturbated bedset character.

Infaunal populations in Chignecto Bay peak in the late spring and in the late summer–early autumn. Both population peaks are exploited by vertebrates, including migrating Atlantic sturgeon (late spring) and migratory shorebirds (late summer–early autumn). In particular, the upper Bay of Fundy, including Chignecto Bay, is a staging ground for approximately 42–74% of the world’s Semipalmated sandpipers (
Calidris pusilla
) on their annual migration from the Arctic to South America. Fortunately, anthropogenic modification of Chignecto Bay, and its associated bays and rivers (e.g. construction and dismantling of a causeway over the Petitcodiac River), has not had a significant effect, to date, on the mud-flat habitat or the infaunal biomass.
Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells
Authors: Bacher Nicole , Raker Verena , Hofmann Claudia , Graulich Edith , Schwenk Melanie , Baumgrass Ria , Bopp Tobias , Zechner Ulrich , Merten Luzie , Becker Christian , Steinbrink Kerstin 
Published: July 2013

AbstractIFN-α is an antineoplastic agent in the treatment of several solid and hematologic malignancies that exerts strong immune- and autoimmune-stimulating activity. However, the mechanisms of immune activation by IFN-α remain incompletely understood, particularly with regard to CD4+CD25highFoxp+ regulatory T cells (Treg). Here, we show that IFN-α deactivates the suppressive function of human Treg by downregulating their intracellular cAMP level. IFN-α–mediated Treg inactivation increased CD4+ effector T-cell activation and natural killer cell tumor cytotoxicity. Mechanistically, repression of cAMP in Treg was caused by IFN-α–induced MAP–ERK kinase (MEK)/extracellular signal-regulated kinase (ERK)–mediated phosphodiesterase 4 (PDE4) activation and accompanied by downregulation of IFN receptor (IFNAR)-2 and negative regulation of T-cell receptor signaling. IFN-α did not affect the anergic state, cytokine production, Foxp3 expression, or methylation state of the Treg-specific demethylated region (TSDR) within the FOXP3 locus associated with a stable imprinted phenotype of human Treg. Abrogated protection by IFN-α–treated Treg in a humanized mouse model of xenogeneic graft-versus-host disease confirmed IFN-α–dependent regulation of Treg activity in vivo. Collectively, the present study unravels Treg inactivation as a novel IFN-α activity that provides a conceivable explanation for the immune-promoting effect and induction of autoimmunity by IFN-α treatment in patients with cancer and suggests IFN-α for concomitant Treg blockade in the context of therapeutic vaccination against tumor antigens. Cancer Res; 73(18); 5647–56. ©2013 AACR.
Redox Imbalance and Biochemical Changes in Cancer
Authors: Jorgenson Tonia C. , Zhong Weixiong , Oberley Terry D. 
Published: July 2013

Abstract
For this article, we explore a hypothesis involving the possible role of reduction/oxidation (redox) state in cancer. We hypothesize that many modifications in cellular macromolecules, observed in cancer progression, may be caused by redox imbalance. Recent biochemical data suggest that human prostate cancer cell lines show a redox imbalance (oxidizing) compared with benign primary prostate epithelial cells; the degree of oxidation varied with aggressive behavior of each cell line. Our recent data suggest that human breast cancer tissues show a redox imbalance (reducing) compared with benign adjacent breast tissues. Accumulating data summarized in this article suggest that redox imbalance may regulate gene expression and alter protein stability by posttranslational modifications, in turn modulating existing cellular programs. Despite significant improvements in cancer therapeutics, resistance occurs, and redox imbalance may play a role in this process. Studies show that some cancer therapeutic agents increase generation of reactive oxygen/nitrogen species and antioxidant enzymes, which may alter total antioxidant capacity, cause cellular adaptation, and result in reduced effectiveness of treatment modalities. Approaches involving modulations of intra- and extracellular redox states, in combination with other therapies, may lead to new treatment options, especially for patients who are resistant to standard treatments. Cancer Res; 73(20); 6118–23. ©2013 AACR.
Clinical and Pharmacogenetic Predictors of Circulating Atorvastatin and Rosuvastatin Concentrations in Routine Clinical Care
Authors: DeGorter Marianne K. , Tirona Rommel G. , Schwarz Ute I. , Choi Yun-Hee , Dresser George K. , Suskin Neville , Myers Kathryn , Zou GuangYong , Iwuchukwu Otito , Wei Wei-Qi , Wilke Russell A. , Hegele Robert A. , Kim Richard B. 
Published: July 2013

Background—
A barrier to statin therapy is myopathy associated with elevated systemic drug exposure. Our objective was to examine the association between clinical and pharmacogenetic variables and statin concentrations in patients.

Methods and Results—

In total, 299 patients taking atorvastatin or rosuvastatin were prospectively recruited at an outpatient referral center. The contribution of clinical variables and transporter gene polymorphisms to statin concentration was assessed using multiple linear regression. We observed 45-fold variation in statin concentration among patients taking the same dose. After adjustment for sex, age, body mass index, ethnicity, dose, and time from last dose,
SLCO1B1
c.521T>C (
P
<0.001) and
ABCG2
c.421C>A (
P
<0.01) were important to rosuvastatin concentration (adjusted
R
2
=0.56 for the final model). Atorvastatin concentration was associated with
SLCO1B1
c.388A>G (
P
<0.01) and c.521T>C (
P
<0.05) and 4β-hydroxycholesterol, a CYP3A activity marker (adjusted
R
2
=0.47). A second cohort of 579 patients from primary and specialty care databases were retrospectively genotyped. In this cohort, genotypes associated with statin concentration were not differently distributed among dosing groups, implying providers had not yet optimized each patient’s risk–benefit ratio. Nearly 50% of patients in routine practice taking the highest doses were predicted to have statin concentrations greater than the 90th percentile.

Conclusions—
Interindividual variability in statin exposure in patients is associated with uptake and efflux transporter polymorphisms. An algorithm incorporating genomic and clinical variables to avoid high atorvastatin and rosuvastatin levels is described; further study will determine whether this approach reduces incidence of statin myopathy.
Drop Shapes and Fall Speeds in Rain: Two Contrasting Examples
Authors: Thurai M. , Bringi V. N. , Petersen W. A. , Gatlin P. N. 
Published: July 2013

AbstractTwo rain events are analyzed using two collocated 2D-video disdrometers (2DVD) and a C-band polarimetric radar at 15-km distance. Both events had moderate-to-intense rainfall rates, but the second event had an embedded convective line. For the first event, the fall speed distribution for a given drop diameter interval showed a narrow and symmetric distribution with a mode at the expected value; the second event produced a wider distribution with a significant skewness toward lower fall speeds. The “slower” drops in the second event were detected while the convective line was directly over the 2DVD site. Drop shape information from the two 2DVD instruments showed that, during the passage of the convection line, around 30%–40% of the drops did not have an axis of rotational symmetry, whereas for event 1, it was only 5%. The implications are that for event 1 the dominant mode of drop oscillation is the axisymmetric mode, and that within the convective line of event 2 other fundamental modes were frequent. The radar data for the second event were analyzed in terms of the self-consistency among the radar-measured quantities. The Kdp/Zh versus Zdr variations within the line convection were not consistent with the corresponding variation determined from the scattering calculations using the measured 1-min drop size distributions and using the “reference” drop shapes. Also found were low ρhv regions within the line convection that were considerably lower than the scattering calculations. These findings are consistent with the asymmetric oscillation modes inferred from the 2DVD measurements for event 2 (probably collision induced) within the convective line.