bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Exposure Induces Inflammasome Pathway Activation in Immune Cells
Authors: Stoecklein Veit M. , Osuka Akinori , Ishikawa Shizu , Lederer Madeline R. , Wanke-Jellinek Lorenz , Lederer James A. 
Published: December 2014

Abstract
Radiation exposure induces cell and tissue damage, causing local and systemic inflammatory responses. Because the inflammasome pathway is triggered by cell death and danger-associated molecular patterns, we hypothesized that the inflammasome may signal acute and chronic immune responses to radiation. Using a mouse radiation model, we show that radiation induces a dose-dependent increase in inflammasome activation in macrophages, dendritic cells, NK cells, T cells, and B cells as judged by cleaved caspase-1 detection in cells. Time course analysis showed the appearance of cleaved caspase-1 in cells by day 1 and sustained expression until day 7 after radiation. Also, cells showing inflammasome activation coexpressed the cell surface apoptosis marker annexin V. The role of caspase-1 as a trigger for hematopoietic cell losses after radiation was studied in caspase-1−/− mice. We found less radiation-induced cell apoptosis and immune cell loss in caspase-1−/− mice than in control mice. Next, we tested whether uric acid might mediate inflammasome activation in cells by treating mice with allopurinol and discovered that allopurinol treatment completely blocked caspase-1 activation in cells. Finally, we demonstrate that radiation-induced caspase-1 activation occurs by a Nod-like receptor family protein 3–independent mechanism because radiation-exposed Nlrp3−/− mice showed caspase-1 activation profiles that were indistinguishable from those of wild-type mice. In summary, our data demonstrate that inflammasome activation occurs in many immune cell types following radiation exposure and that allopurinol prevented radiation-induced inflammasome activation. These results suggest that targeting the inflammasome may help control radiation-induced inflammation.
TSLP Expression: Analysis with a ZsGreen TSLP Reporter Mouse
Authors: Dewas Cedric , Chen Xi , Honda Tetsuya , Junttila Ilkka , Linton Jay , Udey Mark C. , Porcella Stephen F. , Sturdevant Daniel E. , Feigenbaum Lionel , Koo Lily , Williams Joy , Paul William E. 
Published: December 2014

AbstractThymic stromal lymphopoietin (TSLP) is a type I cytokine that plays a central role in induction of allergic inflammatory responses. Its principal targets have been reported to be dendritic cells and/or CD4 T cells; epithelial cells are a principal source. We report in this study the development of a reporter mouse (TSLP-ZsG) in which a ZsGreen (ZsG)-encoding construct has been inserted by recombineering into a bacterial artificial chromosome immediately at the translation initiating ATG of TSLP. The expression of ZsG by mice transgenic for the recombinant BAC appears to be a faithful surrogate for TSLP expression, particularly in keratinocytes and medullary thymic epithelial cells. Limited ZsG and TSLP mRNA was observed in bone marrow–derived mast cells, basophils, and dendritic cells. Using the TSLP-ZsG reporter mouse, we show that TNF-α and IL-4/IL-13 are potent inducers of TSLP expression by keratinocytes and that local activation of Th2 and Th1 cells induces keratinocyte TSLP expression. We suggest that the capacity of TSLP to both induce Th2 differentiation and to be induced by activated Th2 cells raises the possibility that TSLP may be involved in a positive feedback loop to enhance allergic inflammatory conditions.
Phosphatidylinositol 4–Phosphate 5–Kinase α and Vav1 Mutual Cooperation in CD28-Mediated Actin Remodeling and Signaling Functions
Authors: Muscolini Michela , Camperio Cristina , Porciello Nicla , Caristi Silvana , Capuano Cristina , Viola Antonella , Galandrini Ricciarda , Tuosto Loretta 
Published: December 2014

Abstract
Phosphatidylinositol 4,5–biphosphate (PIP2) is a cell membrane phosphoinositide crucial for cell signaling and activation. Indeed, PIP2 is a pivotal source for second messenger generation and controlling the activity of several proteins regulating cytoskeleton reorganization. Despite its critical role in T cell activation, the molecular mechanisms regulating PIP2 turnover remain largely unknown. In human primary CD4+ T lymphocytes, we have recently demonstrated that CD28 costimulatory receptor is crucial for regulating PIP2 turnover by allowing the recruitment and activation of the lipid kinase phosphatidylinositol 4–phosphate 5–kinase (PIP5Kα). We also identified PIP5Kα as a key modulator of CD28 costimulatory signals leading to the efficient T cell activation. In this study, we extend these data by demonstrating that PIP5Kα recruitment and activation is essential for CD28-mediated cytoskeleton rearrangement necessary for organizing a complete signaling compartment leading to downstream signaling functions. We also identified Vav1 as the linker molecule that couples the C-terminal proline-rich motif of CD28 to the recruitment and activation of PIP5Kα, which in turn cooperates with Vav1 in regulating actin polymerization and CD28 signaling functions.
Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Authors: Das Rituparna , Verma Rakesh , Sznol Mario , Boddupalli Chandra Sekhar , Gettinger Scott N. , Kluger Harriet , Callahan Margaret , Wolchok Jedd D. , Halaban Ruth , Dhodapkar Madhav V. , Dhodapkar Kavita M. 
Published: December 2014

Abstract
Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from 45 patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomic and functional signatures in vivo in purified human T cells and monocytes. Therapy-induced changes are more prominent in T cells than in monocytes and involve largely nonoverlapping changes in coding genes, including alternatively spliced transcripts and noncoding RNAs. Pathway analysis revealed that CTLA-4 blockade induces a proliferative signature predominantly in a subset of transitional memory T cells, whereas PD-1 blockade instead leads to changes in genes implicated in cytolysis and NK cell function. Combination blockade leads to nonoverlapping changes in gene expression, including proliferation-associated and chemokine genes. These therapies also have differential effects on plasma levels of CXCL10, soluble IL-2R, and IL-1α. Importantly, PD-1 receptor occupancy following anti–PD-1 therapy may be incomplete in the tumor T cells even in the setting of complete receptor occupancy in circulating T cells. These data demonstrate that, despite shared property of checkpoint blockade, Abs against PD-1, CTLA-4 alone, or in combination have distinct immunologic effects in vivo. Improved understanding of pharmacodynamic effects of these agents in patients will support rational development of immune-based combinations against cancer.
Cutting Edge: Maresin-1 Engages Regulatory T Cells To Limit Type 2 Innate Lymphoid Cell Activation and Promote Resolution of Lung Inflammation
Authors: Krishnamoorthy Nandini , Burkett Patrick R. , Dalli Jesmond , Abdulnour Raja-Elie E. , Colas Romain , Ramon Sesquile , Phipps Richard P. , Petasis Nicos A. , Kuchroo Vijay K. , Serhan Charles N. , Levy Bruce D. 
Published: December 2014

Abstract
Asthma is a chronic inflammatory disease that fails to resolve. Recently, a key role for type 2 innate lymphoid cells (ILC2s) was linked to asthma pathogenesis; however, mechanisms for ILC2 regulation remain to be determined. In this study, metabololipidomics of murine lungs identified temporal changes in endogenous maresin 1 (MaR1) during self-limited allergic inflammation. Exogenous MaR1 reduced lung inflammation and ILC2 expression of IL-5 and IL-13 and increased amphiregulin. MaR1 augmented de novo generation of regulatory T cells (Tregs), which interacted with ILC2s to markedly suppress cytokine production in a TGF-β–dependent manner. Ab-mediated depletion of Tregs interrupted MaR1 control of ILC2 expression of IL-13 in vivo. Together, the findings uncover Tregs as potent regulators of ILC2 activation; MaR1 targets Tregs and ILC2s to restrain allergic lung inflammation, suggesting MaR1 as the basis for a new proresolving therapeutic approach to asthma and other chronic inflammatory diseases.
Echocardiographic Evaluation of Aortic Atheromas in Patients With Aortic Stenosis
Authors: Vizzardi Enrico , D'Aloia Antonio , Sciatti Edoardo , Bonadei Ivano , Gelsomino Sandro , Lorusso Roberto , Metra Marco 
Published: December 2014

ObjectivesThe association of aortic atheromas in patients with isolated aortic stenosis has recently been acknowledged, probably because the pathogenic mechanisms are similar. Therefore, this study evaluated the extent and severity of thoracic aortic atheromas in patients with different grades of aortic stenosis using transesophageal echocardiography.MethodsWe retrospectively evaluated transesophageal echocardiographic examinations of 686 consecutive patients with a diagnosis of aortic stenosis. The prevalence and morphologic characteristics of atheromas in 3 segments of the thoracic aorta were assessed. Plaque thickness was measured at each segment, and the thickest plaque was used to establish severity. Atheromas were graded as mild, moderate, or severe according to plaque thickness (<2, 2–4, or >4 mm, respectively). Aortic stenosis was graded as mild, moderate, or severe on the basis of the gradient and anatomic aortic valve area (>1.5, 1.0–1.5, or <1.0 cm2).ResultsA total of 382 patients were men, and 304 were women (mean age ± SD, 74 ± 15 years); 86% of the patients had aortic atheromas. The severe stenosis group had a significantly higher rate of atheromas (95% versus 40%; P < .001) than the mild stenosis group, with more complex atheromas (52% versus 22%; P< .001). There was no significant difference in the atheroma grades between the severe and moderate stenosis groups, but moderate cases had more moderate and severe atheromas than mild cases (45% and 15% versus 19% and 3%; P < .01).ConclusionsThis study showed a correlation in the extent of aortic atheromas across several degrees of aortic stenosis. Patients with moderate and severe stenosis had more extensive atherosclerotic atheromas than those with mild stenosis.
Comparison of Lesion Detection in the Transverse and Coronal Views on Automated Breast Sonography
Authors: Chae Eun Young , Cha Joo Hee , Kim Hak Hee , Shin Hee Jung 
Published: December 2014

ObjectivesThe purpose of our study was to compare the accuracy of detection of lesions in the coronal and transverse views on automated breast sonography.MethodsThree breast radiologists independently interpreted automated breast sonograms from 113 women: 14 with negative findings and 99 with known breast lesions (99 benign and 53 malignant findings). The readers were asked to detect the presence or absence of the abnormalities using the transverse and coronal views in different reading sessions. If a lesion was detected, we evaluated its location, sonographic features, including shape, orientation, margin, boundary type, and echo pattern, and final American College of Radiology Breast Imaging Reporting and Data System assessment category. The reading time was also evaluated.ResultsOf 456 potential detections (152 lesions with 3 readers), 80.5% of the detections were made with the transverse view, and 67.3% were made with the coronal view. The detection rates for both malignant and benign lesions were significantly higher for the transverse view than for the coronal view (P < .001). The reading time for the coronal view was less than that for the transverse view (mean ± SD, 3.83 ± 1.71 versus 5.57 ± 2.21 minutes). The intraclass correlation coefficient values for lesion location, distance from the nipple, and lesion size for both views all exceeded 0.7.ConclusionsAlthough the coronal view on automated breast sonography showed comparable reliability and a shorter reading time, the detection rate for the coronal view was significantly lower than that for the transverse view in both benign and malignant lesions. It is preferable to reserve the coronal view as an additional method to the transverse view.
Chorionic Bump on First‐Trimester Sonography
Authors: Arleo Elizabeth Kagan , Troiano Robert N. 
Published: December 2014

ObjectivesThe purpose of this study was to determine the live birth rate of pregnancies with a diagnosis of a chorionic bump, a convex bulge from the choriodecidual surface into the first‐trimester gestational sac.MethodsPregnant patients at least 18 years old with the finding of a chorionic bump on first‐trimester sonography were included in this prospective observational study. The independent variables were chorionic bump size and number and presence or absence of a history of infertility or coagulation disorder. The primary end point was pregnancy outcome.ResultsDuring the 4‐year study period, 52 pregnancies had a diagnosis of a chorionic bump. Overall, 34 resulted in live births, corresponding to an absolute live birth rate of 65%, and 18 were nonviable. Forty‐one chorionic bump pregnancies were otherwise normal (ie, pregnancies in which a gestational sac, yolk sac, and embryo with heartbeat were seen at some point), and in this subset, the live birth rate was 83% (34 of 41). All pregnancies with more than 1 chorionic bump (4) ended in demise (100%). The average maximum dimension of the chorionic bump was 1.3 cm (range, 0.5–3.8 cm); however there was not a statistically significant correlation between chorionic bump size and pregnancy outcome (P = .5866; odds ratio, 0.54; 95% confidence interval, 0.06–5.01). Nine patients (17%) had a history of infertility treatment, and 4 (8%) had a history of coagulation disorder. Only 1 chorionic bump pregnancy was associated with a birth defect.ConclusionsThe live birth rate in our chorionic bump cohort was 65% overall and even higher (83%) if the pregnancy was otherwise normal. The clinical implication is that a chorionic bump on first‐trimester sonography is not necessarily associated with a guarded prognosis.
Detailed Transabdominal Fetal Anatomic Scanning in the Late First Trimester Versus the Early Second Trimester of Pregnancy
Authors: Yagel Simcha , Cohen Sarah M. , Porat Shay , Daum Hagit , Lipschuetz Michal , Amsalem Hagai , Messing Baruch , Valsky Dan V. 
Published: December 2014

ObjectivesTo compare visualization rates for early targeted organ scanning at gestational ages ranging from 11 weeks 3 days to 13 weeks 2 days versus 14 weeks 3 days to 16 weeks 2 days.MethodsWe conducted a prospective longitudinal study of patients who presented for nuchal translucency (NT) screening and targeted organ scanning. Extended targeted organ scanning, including the central nervous system, face and neck, chest, heart (including complete echocardiography), digestive system, abdominal wall, urinary system, skeleton, and umbilical cord with its insertion and placenta, was performed on gravidas in 2 age ranges. Uterine artery Doppler mapping was performed during the second scan. All cases were examined twice: once at NT screening (up to 13 weeks 2 days) and again in the early second trimester.ResultsA total of 408 women were recruited and scanned twice. Three abnormalities were diagnosed in the second scan that were not seen in the first: dysplastic long bones, tricuspid stenosis, and cleft lip (without palate involvement). None had chromosomal anomalies. Successful visualization rates in all organ systems exceeded 94% in the second trimester. At the first‐trimester scan, some systems had high success rates, whereas others were very low; eg, in the brain, the cerebellum and posterior fossa were visualized successfully approximately 50% of the time and the upper lip only approximately 10%. On fetal echocardiography, the 4‐chamber view and outflow tracts were imaged successfully approximately 40% of the time, and the kidneys approximately 35%. Uterine artery Doppler mapping was possible in all patients on at least one side. On third‐trimester follow‐up, we diagnosed 1 mild pulmonary stenosis, 1 autosomal recessive polycystic kidney disease, and 1 ventricular septal defect.ConclusionsThe early second‐trimester scan was much more productive than targeted organ scanning performed during the NT window. When counseling women regarding the optimal time for early transabdominal targeted organ scanning, successful visualization rates for various organ systems should be considered.
Factors Affecting the Feasibility of Routine First‐Trimester Fetal Echocardiography
Authors: Nemescu Dragos , Onofriescu Mircea 
Published: December 2014

ObjectivesThe purpose of our study was to assess the factors that may improve the feasibility of routine fetal echocardiography at the time of the first‐trimester scan.MethodsIn this prospective study, we included 616 healthy singleton fetuses. Examinations were performed transabdominally by a single sonographer at the beginning of his training in first‐trimester screening. The fetal heart was examined by high‐definition color Doppler imaging to obtain the 4‐chamber view, right and left ventricular outflow tracts, and 3‐vessel and trachea view. Logistic regression was used to investigate the effect on the ability to visualize different cardiac structures.ResultsThe frequency of successful heart examinations increased significantly with the number of scans performed (P < .05). The sonographer needed 180 examinations before he could successfully examine the heart in at least 80% of cases. Significant factors that increased the probability of adequate echocardiography were the length of the heart examination and the experience of the sonographer (P< .05) but not transducer‐heart distance, maternal body mass index, fetal crown‐rump length, placenta interposition, or restrictive fetal position. Visualization of the left ventricular outflow tract could be improved by increasing the experience of the sonographer and decreasing the transducer‐heart distance. Also, visualization of the 3‐vessel and trachea view depended on the length of the heart examination, the experience of the sonographer, an anterior position of the placenta, and a restrictive fetal position.ConclusionsCompetence in color flow mapping assessment of the fetal heart at gestational ages of 11 weeks to 13 weeks 6 days is achieved only after extensive supervised training.
A Taller‐Than‐Wide Shape Is a Good Predictor of Papillary Thyroid Carcinoma in Small Solid Nodules
Authors: Ren Jie , Liu Bin , Zhang Li-Li , Li Hong-Yu , Zhang Fan , Li Shuang , Zhao Li-Rong 
Published: December 2014

ObjectivesThe purpose of this study was to evaluate whether a nodule with a taller‐than‐wide shape (ie, an anteroposterior diameter that is longer than the transverse diameter on a transverse or longitudinal plane [anteroposterior‐to‐transverse ratio] >1) is a good predictor of papillary thyroid carcinoma (PTC) according to nodule size.MethodsWe retrospectively examined 207 thyroid nodules in our hospital from September 2011 to February 2013. Nodules were divided into groups by size: small (≤0.5 cm; group A), medium (0.5–1 cm; group B), and large (>1 cm; group C). Sonographic features were defined as an anteroposterior‐to‐transverse ratio greater than 1, microcalcifications, blurred margins, and hypoechogenicity.ResultsAn anteroposterior‐to‐transverse ratio greater than 1 was the most accurate sonographic feature for predicting PTC in small nodules, with high sensitivity (81.4%) and specificity (96.8%), but it was not accurate in large nodules (>1 cm). Microcalcifications showed higher sensitivity (P< .05) in large nodules (60.0%) than in small ones (27.9%). Hypoechogenicity and blurred margins showed high sensitivity (95.3% and 97.7%, respectively) but low specificity (19.4% and 29.9%) for diagnosis of PTC in small thyroid nodules. An anteroposterior‐to‐transverse ratio greater than 1 in conjunction with another sonographic feature achieved the highest diagnostic accuracy in small nodules.ConclusionsThe predictive values of sonographic features depend on nodule size. An anteroposterior‐to‐transverse ratio greater than 1, especially in conjunction with another sonographic risk factor, showed superior performance for PTC diagnosis in small nodules.
A Novel Approach to Patient Self‐Monitoring of Sonographic Examinations Using a Head‐Mounted Display
Authors: Inoue Masaharu , Kihara Kazunori , Yoshida Soichiro , Ito Masaya , Takeshita Hideki , Ishioka Junichiro , Matsuoka Yoh , Numao Noboru , Saito Kazutaka , Fujii Yasuhisa 
Published: December 2014

ObjectivesPatients' use of a head‐mounted display during their sonographic examinations could provide them with information about their diseases in real time and might help improve “patient‐centered care.” We conducted this prospective study to evaluate the feasibility of a modern head‐mounted display for patient self‐monitoring of sonographic examinations.MethodsIn November and December 2013, 58 patients were enrolled. Patients wore a head‐mounted display (HMZ‐T2; Sony Corporation, Tokyo, Japan) during their sonographic examinations and watched their own images in real time. After the sonographic examinations, the patients completed a questionnaire, in which they evaluated the utility of the head‐mounted display, their understanding of their diseases, their satisfaction with using the head‐mounted display, and any adverse events. Until November 26, 2013, patients' names were requested on the questionnaire; after that date, the questionnaire was changed to be anonymous.ResultsOf the 58 patients, 56 (97%) elected to participate in this study. The head‐mounted display was reported to have good image quality by 42 patients (75%) and good wearability by 39 (70%). Thirty‐six patients (64%) reported they had deepened their understanding of their diseases. There were no major complications, and only 2 patients (4%) had mild eye fatigue. There was no significant association between questionnaire results and patient characteristics. None of the questionnaire results changed significantly after the questionnaire was made anonymous.ConclusionsThe use of a modern head‐mounted display by patients during sonographic examinations provided good image quality with acceptable wearability. It could deepen their understanding of their diseases and help develop patient‐centered care.
Differentiation of Metastatic Cervical Lymph Nodes With Ultrasound Elastography by Virtual Touch Tissue Imaging
Authors: Che Dehong , Zhou Xianli , Sun Mei-Ling , Wang Xiao , Jiang Zhaopeng , Changjun-Wu  
Published: December 2014

ObjectivesThe purpose of this study was to investigate the clinical usefulness of acoustic radiation force impulse elastography for the differential diagnosis of cervical lymph nodes.MethodsVirtual touch tissue imaging (Siemens Medical Solutions, Mountain View, CA) was analyzed in 81 patients (mean age, 46.6 years; range, 5–82 years) with 81 lymph nodes (45 metastatic nodes and 36 benign nodes).ResultsMost benign lymph nodes were slightly darker or the same in brightness compared with surrounding tissue, whereas most metastatic nodes were obviously darker. The mean area ratio of benign lymph nodes ± SD (1.05 ± 0.15) was statistically lower than the mean area ratio of metastatic lymph nodes (1.39 ± 0.20; P < 0.001). The area ration cutoff level for metastatic lymph nodes was estimated to be 1.16. With the use of a receiver operating characteristic curve with this cutoff value, the area ratio predicted malignancy with sensitivity of 91.1%, specificity of 83.3%, and an area under the curve of 0.925.ConclusionsAcoustic radiation force impulse imaging is feasible for cervical lymph nodes. The Virtual Touch tissue imaging technique can complement conventional sonography, thereby making it easier to diagnose cervical lymph nodes.