bluuebunny/crossref_metadata_2025_split huggingface dataset:
GiardiaInfection of the Small Intestine Induces Chronic Colitis in Genetically Susceptible Hosts
Authors: Dann Sara M. , Le Christine H. Y. , Hanson Elaine M. , Ross Matthew C. , Eckmann Lars 
Published: June 2018

AbstractThe lumen-dwelling protozoan Giardia is an important parasitic cause of diarrheal disease worldwide. Infection can persist over extended periods with minimal intestinal inflammation, suggesting that Giardia may attenuate host responses to ensure its survival, although clearance eventually occurs in most cases. IL-10 is an anti-inflammatory regulator critical for intestinal homeostasis and controlling host responses to bacterial exposure, yet its potential role in coordinating antiprotozoal host defense in the intestine is not known. In this study, we found that murine infection with the natural enteric pathogen Giardia muris induced a transient IL-10 response after 2–4 wk at the primary site of infection in the upper small intestine, but parasite colonization and eradication were not affected by the absence of the cytokine in gene-targeted mice. However, IL-10 was critical for controlling infection-associated immunological sequelae in the colon because severe and persistent diarrhea and colitis were observed in IL-10–deficient mice within 1–2 wk postinfection but not in uninfected littermate controls. Inflammation was characterized by epithelial hyperplasia, neutrophil and macrophage expansion, and Th1 induction and could be prevented by blockade of IL-12/IL-23 p40 but not depletion of CD11c+ dendritic cells. Furthermore, the intestinal microbiota underwent characteristic shifts in composition and was required for disease because antibiotics and loss of TLR signaling in MyD88-deficient mice protected against colitis. Together, our data suggest that transient infection by a luminal and seemingly noninflammatory pathogen can trigger sustained colitis in genetically susceptible hosts, which has broader implications for understanding postinfectious syndromes and other chronic intestinal inflammatory conditions.
Myeloid Cell–Restricted STAT3 Signaling Controls a Cell-Autonomous Antifibrotic Repair Program
Authors: Do Nhu-Nguyen , Willenborg Sebastian , Eckes Beate , Jüngst Christian , Sengle Gerhard , Zaucke Frank , Eming Sabine A. 
Published: June 2018

Abstract
Myeloid cells can be beneficial as well as harmful in tissue regenerative responses. The molecular mechanisms by which myeloid cells control this critical decision of the immune system are not well understood. Using two different models of physiological acute or pathological chronic skin damage, in this study we identified myeloid cell–restricted STAT3 signaling as important and an injury context–dependent regulator of skin fibrosis. Targeted disruption of STAT3 signaling in myeloid cells significantly accelerated development of pathological skin fibrosis in a model of chronic bleomycin-induced tissue injury, whereas the impact on wound closure dynamics and quality of healing after acute excision skin injury was minor. Chronic bleomycin-mediated tissue damage in control mice provoked an antifibrotic gene signature in macrophages that was characterized by upregulated expression of IL-10, SOCS3, and decorin. In contrast, in STAT3-deficient macrophages this antifibrotic repair program was abolished whereas TGF-β1 expression was increased. Notably, TGF-β1 synthesis in cultured control bone marrow–derived macrophages (BMDMs) was suppressed after IL-10 exposure, and this suppressive effect was alleviated by STAT3 deficiency. Accordingly, coculture of IL-10–stimulated control BMDMs with fibroblasts suppressed expression of the TGF-β1 downstream target connective tissue growth factor in fibroblasts, whereas this suppressive effect was lost by STAT3 deficiency in BMDMs. Our findings highlight a previously unrecognized protective role of myeloid cell–specific STAT3 signaling in immune cell–mediated skin fibrosis, and its regulatory pathway could be a potential target for therapy.
Detecting Rare AID-Induced Mutations in B-Lineage Oncogenes from High-Throughput Sequencing Data Using the Detection of Minor Variants by Error Correction Method
Authors: Martin Ophélie Alyssa , Garot Armand , Le Noir Sandrine , Aldigier Jean-Claude , Cogné Michel , Pinaud Eric , Boyer François 
Published: June 2018

Abstract
In B-lineage cells, the cytidine deaminase AID not only generates somatic mutations to variable regions of Ig genes but also inflicts, at a lower frequency, mutations to several non-Ig genes named AID off-targets, which include proto-oncogenes. High-throughput sequencing should be in principle the method of choice to detect and document these rare nucleotide substitutions. So far, high-throughput sequencing–based methods are impaired by a global sequencing error rate that usually covers the real mutation rate of AID off-target genes in activated B cells. We demonstrate the validity of a per-base background subtraction method called detection of minor variants by error correction (DeMinEr), which uses deep sequencing data from mutated and nonmutated samples to correct the substitution frequency at each nucleotide position along the sequenced region. Our DeMinEr method identifies somatic mutations at a frequency down to 0.02% at any nucleotide position within two off-target genes: Cd83 and Bcl6. Biological models and control conditions such as AID- and UNG-deficient mice validate the specificity and the sensitivity of our method. The high resolution and robustness of DeMinEr enable us to document fine effects such as age-dependent accumulation of mutations in these oncogenes in the mouse.
Kidney Proximal Tubular TLR9 Exacerbates Ischemic Acute Kidney Injury
Authors: Han Sang Jun , Li Hongmei , Kim Mihwa , Shlomchik Mark J. , Lee H. Thomas 
Published: June 2018

Abstract
The role for kidney TLR9 in ischemic acute kidney injury (AKI) remains unclear. In this study, we tested the hypothesis that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular epithelial apoptosis and inflammation. To test this hypothesis, we generated mice lacking TLR9 in renal proximal tubules (TLR9fl/fl PEPCK Cre mice). Contrasting previous studies in global TLR9 knockout mice, mice lacking renal proximal tubular TLR9 were protected against renal ischemia/reperfusion (IR) injury, with reduced renal tubular necrosis, inflammation (decreased proinflammatory cytokine synthesis and neutrophil infiltration), and apoptosis (decreased DNA fragmentation and caspase activation) when compared with wild-type (TLR9fl/fl) mice. Consistent with this, a selective TLR9 agonist oligonucleotide 1668 exacerbated renal IR injury in TLR9fl/fl mice but not in renal proximal tubular TLR9-null mice. Furthermore, in cultured human and mouse proximal tubule cells, TLR9-selective ligands induced NF-κB activation, proinflammatory cytokine mRNA synthesis, as well as caspase activation. We further confirm in the present study that global TLR9 deficiency had no impact on murine ischemic AKI. Taken together, our studies show that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular inflammation, apoptosis as well as necrosis, after IR via NF-κB and caspase activation. Our studies further suggest the complex nature of TLR9 activation, as renal tubular epithelial TLR9 promotes cell injury and death whereas TLR9 signaling in other cell types may promote cytoprotective effects.
Antibody Inhibition of Properdin Prevents Complement-Mediated Intravascular and Extravascular Hemolysis
Authors: Gullipalli Damodar , Zhang Fengkui , Sato Sayaka , Ueda Yoshiyasu , Kimura Yuko , Golla Madhu , Miwa Takashi , Wang Jianxiang , Song Wen-Chao 
Published: June 2018

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a serious blood disorder characterized by dysregulated complement activation on blood cells. Eculizumab, the current standard therapy and a humanized anti-C5 mAb, relieves anemia and thrombosis symptoms of PNH patients by preventing complement-dependent intravascular hemolysis (IVH). However, up to 20% of PNH patients on long-term eculizumab treatment still suffer from significant anemia and are transfusion dependent because of extravascular hemolysis (EVH) of C3-opsonized PNH erythrocytes. In this study, we show that function-blocking anti-properdin (P) mAbs dose-dependently inhibited autologous, complement-mediated hemolysis induced by factor H dysfunction. Furthermore, anti–human P (hP) mAbs potently and dose-dependently inhibited acidified serum–induced hemolysis of PNH erythrocytes (Ham test). In contrast to erythrocytes rescued by anti-C5 mAb, nonlysed PNH erythrocytes rescued by anti-P mAb incurred no activated C3 fragment deposition on their surface. These results suggested that anti-P mAbs may prevent EVH as well as IVH of PNH erythrocytes. To test the in vivo efficacy of anti-hP mAbs in preventing EVH, we generated a P humanized mouse by transgenic expression of hP in P knockout mice (hP-Tg/P−/−). In a murine EVH model, complement-susceptible erythrocytes were completely eliminated within 3 d in control mAb-treated hP-Tg/P−/− mice, whereas such cells were protected and persisted in hP-Tg/P−/− mice treated with an anti-hP mAb. Collectively, these data suggest that anti-P mAbs can inhibit both IVH and EVH mediated by complement and may offer improved efficacy over eculizumab, the current standard therapy for PNH.
Early Generated B-1–Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma–like Neoplasia in Aged Mice
Authors: Hayakawa Kyoko , Formica Anthony M. , Nakao Yuka , Ichikawa Daiju , Shinton Susan A. , Brill-Dashoff Joni , Smith Mitchell R. , Morse Herbert C. , Hardy Richard R. 
Published: June 2018

Abstract
In mice, fetal/neonatal B-1 cell development generates murine CD5+ B cells (B1a) with autoreactivity. We analyzed B1a cells at the neonatal stage in a VH11/D/JH knock-in mouse line (VH11t) that generates an autoreactive antiphosphatidylcholine BCR. Our study revealed that antiphosphatidylcholine B1a cells develop in liver, mature in spleen, and distribute in intestine/colon, mesenteric lymph node (mLN), and body cavity as the outcome of B-1 cell development before B-2 cell development. Throughout life, self-renewing B-1 B1a cells circulate through intestine, mesenteric vessel, and blood. The body cavity–deposited B1a cells also remigrate. In old age, some B1a cells proceed to monoclonal B cell lymphocytosis. When neonatal B-1 B1a cells express an antithymocyte/Thy-1 autoreactivity (ATA) BCR transgene in the C.B17 mouse background, ATA B cells increase in PBL and strongly develop lymphomas in aging mice that feature splenomegaly and mLN hyperplasia with heightened expression of CD11b, IL-10, and activated Stat3. At the adult stage, ATA B cells were normally present in the mantle zone area, including in intestine. Furthermore, frequent association with mLN hyperplasia suggests the influence by intestinal microenvironment on lymphoma development. When cyclin D1 was overexpressed by the Eμ-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgMhiIgDloCD5+CD23−CD43+ cells, resembling aggressive human mantle cell lymphoma. Thus, our findings reveal that early generated B cells, as an outcome of B-1 cell development, can progress to become lymphocytosis, lymphoma, and mantle cell lymphoma–like neoplasia in aged mice.
Work-Related Injury and Management Strategies Among Certified Athletic Trainers
Authors: Kucera Kristen L. , Lipscomb Hester J. , Roos Karen G. , Dement John M. , Hootman Jennifer M. 
Published: June 2018

Context:
Health care workers have high rates of musculoskeletal injuries, but many of these injuries go unreported to workers' compensation and national surveillance systems. Little is known regarding the work-related injuries of certified athletic trainers (ATs).

Objective:
To determine the 12-month incidence and prevalence of work-related injuries and describe injury-reporting and -management strategies.

Design:
Cross-sectional study.

Setting:
Population-based online survey.

Patients or Other Participants:
Of the 29 051 ATs currently certified by the Board of Certification, Inc, who “opted in” to research studies, we randomly selected 10 000. Of these, 1826 (18.3%) ATs currently working in the clinical setting were eligible and participated in the baseline survey.

Main Outcome Measure(s):
An online survey was e-mailed in May of 2012. We assessed self-reported work-related injuries in the previous 12 months and management strategies including medical care, work limitations or modifications, and time off work. Statistics (frequencies and percentages) were calculated to describe injury rates per 200 000 work hours, injury prevalence, injury characteristics, and injury-reporting and -management strategies.

Results:
A total of 247 ATs reported 419 work-related injuries during the previous 12 months, for an incidence rate of 21.6 per 200 000 hours (95% confidence interval = 19.6, 23.7) and injury prevalence of 13.5% (95% confidence interval = 12.0%, 15.1%). The low back (26%), hand/fingers (9%), and knee (9%) were frequently affected body sites. Injuries were most often caused by bodily motion/overexertion/repetition (52%), contact with objects/equipment/persons (24%), or slips/trips/falls (15%). More than half of injured ATs (55.5%) sought medical care, 25% missed work, and most (77%) did not file a workers' compensation claim for their injury. Half of injured ATs were limited at work (n = 125), and 89% modified or changed their athletic training work as a result of the injury.

Conclusions:
More than half of AT work-related injuries required medical care or work limitations and were not reported for workers' compensation. Understanding how ATs care for and manage their work-related injuries is important given that few take time off work.
Passive Hip Range-of-Motion Values Across Sex and Sport
Authors: Hogg Jennifer A. , Schmitz Randy J. , Nguyen Anh-Dung , Shultz Sandra J. 
Published: June 2018

Context: Greater passive hip range of motion (ROM) has been associated with greater dynamic knee valgus and thus the potential for increased risk of anterior cruciate ligament injuries. Normative data for passive hip ROM by sex are lacking.Objective: To establish and compare passive hip ROM values by sex and sport and to quantify side-to-side differences in internal-rotation ROM (ROMIR), external-rotation ROM (ROMER), and total ROM (ROMTOT).Design: Cross-sectional study.Setting: Station-based, preparticipation screening.Patients or Other Participants: A total of 339 National Collegiate Athletic Association Division I athletes, consisting of 168 women (age = 19.2 ± 1.2 years, height = 169.0 ± 7.2 cm, mass = 65.3 ± 10.2 kg) and 171 men (age = 19.4 ± 1.3 years, height = 200.0 ± 8.6 cm, mass = 78.4 ± 12.0 kg) in 6 sports screened over 3 years: soccer (58 women, 67 men), tennis (20 women, 22 men), basketball (28 women, 22 men), softball or baseball (38 women, 31 men), cross-country (18 women, 19 men), and golf (6 women, 10 men).Main Outcome Measure(s): Passive hip ROM was measured with the athlete lying prone with the hip abducted to 20° to 30° and knee flexed to 90°. The leg was passively internally and externally rotated until the point of sacral movement. Three measures were averaged for each direction and leg and used for analysis. We compared ROMIR, ROMER, ROMTOT (ROMTOT = ROMIR + ROMER), and relative ROM (ROMREL = ROMIR − ROMER) between sexes and among sports using separate 2 × 6 repeated-measures analyses of variance.Results: Women had greater ROMIR (38.1° ± 8.2° versus 28.6° ± 8.4°; F1,327 = 91.74, P &lt; .001), ROMTOT (72.1° ± 10.6° versus 64.4° ± 10.1°; F1,327 = 33.47, P &lt; .001), and ROMREL (1.5° ± 16.0° versus −7.6° ± 16.5°; F1,327 = 37.05, P &lt; .001) than men but similar ROMER (34.0° ± 12.2° versus 35.8° ± 11.5°; F1,327 = 1.65, P = .20) to men. Cross-country athletes exhibited greater ROMIR (37.0° ± 9.3° versus 30.9° ± 9.4° to 33.3° ± 9.5°; P = .001) and ROMREL (5.9° ± 18.3° versus −9.6° ± 16.9° to −2.7° ± 17.3°; P = .001) and less ROMER (25.7° ± 7.5° versus 35.0° ± 13.0° to 40.2° ± 12.0°; P &lt; .001) than basketball, soccer, softball or baseball, and tennis athletes. They also displayed less ROMTOT (62.7° ± 8.1° versus 70.0° ± 9.1° to 72.9° ± 11.9°; P &lt; .001) than basketball, softball or baseball, and tennis athletes.Conclusions: Women had greater ROMIR than men, resulting in greater ROMTOT and ROMREL. Researchers should examine the extent to which this greater bias toward ROMIR may explain women's greater tendency for dynamic knee valgus. With the exception of cross-country, ROM values were similar across sports. The clinical implications of these aberrant cross-country values require further study.
The influence of behavioural intention on third-party e-commerce payment
Authors: Chen Jih K. 
Published: June 2018

Background: Third-party e-commerce payment has been used by many businesses and consumers, enabling customers to easily access the payment platform during e-commerce transactions. Thus, the emergence of such new technology has become a major topic for organisations to study factors that have influenced the people’s adoption and acceptance of new technology as well as mutual influence. Setting: The Technology Acceptance Model is one of the most studied models of behavioural intention to use new information technology. Aim: However, in terms of the causal relationship of variables in the model, one variable is considered independent, ignoring the possibility of mutual influence, and many samples are required for statistical empirical research. This study aims to resolve these above two deficiencies. Methods: This study adopts the Decision-Making and Trial Evaluation Laboratory method, and applies the latest Technology Acceptance Model (TAM3) to examine. Results: The results found several extra causal relationships which are not present in the TAM3 model, and understood that Experience and Computer Playfulness are the driving factors of third-party e-commerce payment, and Computer Anxiety is the core factor. Conclusion: The feasibility of this approach was demonstrated through an empirical study, and these results could be used to guide management direction and marketing strategy.
Sensitivity of atmospheric aerosol scavenging to precipitation intensity and frequency in the context of global climate change
Authors: Hou Pei , Wu Shiliang , McCarty Jessica L. , Gao Yang 
Published: June 2018

Abstract. Wet deposition driven by precipitation is an important sink for atmospheric aerosols and soluble gases. We investigate the sensitivity of atmospheric aerosol lifetimes to precipitation intensity and frequency in the context of global climate change. Our sensitivity model simulations, through some simplified perturbations to precipitation in the GEOS-Chem model, show that the removal efficiency and hence the atmospheric lifetime of aerosols have significantly higher sensitivities to precipitation frequencies than to precipitation intensities, indicating that the same amount of precipitation may lead to different removal efficiencies of atmospheric aerosols. Combining the long-term trends of precipitation patterns for various regions with the sensitivities of atmospheric aerosol lifetimes to various precipitation characteristics allows us to examine the potential impacts of precipitation changes on atmospheric aerosols. Analyses based on an observational dataset show that precipitation frequencies in some regions have decreased in the past 14 years, which might increase the atmospheric aerosol lifetimes in those regions. Similar analyses based on multiple reanalysis meteorological datasets indicate that the changes of precipitation intensity and frequency over the past 30 years can lead to perturbations in the atmospheric aerosol lifetimes by 10 % or higher at the regional scale.
The Community Cloud retrieval for CLimate (CC4CL) – Part 2: The optimal estimation approach
Authors: McGarragh Gregory R. , Poulsen Caroline A. , Thomas Gareth E. , Povey Adam C. , Sus Oliver , Stapelberg Stefan , Schlundt Cornelia , Proud Simon , Christensen Matthew W. , Stengel Martin , Hollmann Rainer , Grainger Roy G. 
Published: June 2018

Abstract. The Community Cloud retrieval for Climate (CC4CL) is a cloud property retrieval system for satellite-based multispectral imagers and is an important component of the Cloud Climate Change Initiative (Cloud_cci) project. In this paper we discuss the optimal estimation retrieval of cloud optical thickness, effective radius and cloud top pressure based on the Optimal Retrieval of Aerosol and Cloud (ORAC) algorithm. Key to this method is the forward model, which includes the clear-sky model, the liquid water and ice cloud models, the surface model including a bidirectional reflectance distribution function (BRDF), and the "fast" radiative transfer solution (which includes a multiple scattering treatment). All of these components and their assumptions and limitations will be discussed in detail. The forward model provides the accuracy appropriate for our retrieval method. The errors are comparable to the instrument noise for cloud optical thicknesses greater than 10. At optical thicknesses less than 10 modeling errors become more significant. The retrieval method is then presented describing optimal estimation in general, the nonlinear inversion method employed, measurement and a priori inputs, the propagation of input uncertainties and the calculation of subsidiary quantities that are derived from the retrieval results. An evaluation of the retrieval was performed using measurements simulated with noise levels appropriate for the MODIS instrument. Results show errors less than 10 % for cloud optical thicknesses greater than 10. Results for clouds of optical thicknesses less than 10 have errors up to 20 %.
Climate sensitivity and meridional overturning circulation in the late Eocene using GFDL CM2.1
Authors: Hutchinson David K. , de Boer Agatha M. , Coxall Helen K. , Caballero Rodrigo , Nilsson Johan , Baatsen Michiel 
Published: June 2018

Abstract. The Eocene–Oligocene transition (EOT), which took place approximately 34 Ma ago, is an
interval of great interest in Earth's climate history, due to the inception
of the Antarctic ice sheet and major global cooling. Climate
simulations of the transition are needed to help interpret proxy data,
test mechanistic hypotheses for the transition and determine the climate
sensitivity at the time. However, model studies of the EOT thus far typically
employ control states designed for a different time period, or ocean
resolution on the order of 3∘. Here we developed a new higher
resolution palaeoclimate model configuration based on the GFDL CM2.1 climate
model adapted to a late Eocene (38 Ma) palaeogeography reconstruction. The
ocean and atmosphere horizontal resolutions are 1∘ × 1.5∘
and 3∘ × 3.75∘ respectively. This represents a
significant step forward in resolving the ocean geography, gateways and
circulation in a coupled climate model of this period. We run the model under
three different levels of atmospheric CO2: 400, 800 and 1600 ppm. The model
exhibits relatively high sensitivity to CO2 compared with other recent
model studies, and thus can capture the expected Eocene high latitude warmth
within observed estimates of atmospheric CO2. However, the model does
not capture the low meridional temperature gradient seen in proxies.
Equatorial sea surface temperatures are too high in the model
(30–37 ∘C) compared with observations (max 32 ∘C), although
observations are lacking in the warmest regions of the western Pacific. The
model exhibits bipolar sinking in the North Pacific and Southern Ocean, which
persists under all levels of CO2. North Atlantic surface salinities are
too fresh to permit sinking (25–30 psu), due to surface transport from the
very fresh Arctic (∼ 20 psu), where surface salinities
approximately agree with Eocene proxy estimates. North Atlantic salinity
increases by 1–2 psu when CO2 is halved, and similarly freshens when
CO2 is doubled, due to changes in the hydrological cycle.