bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safely ruling out inflammatory bowel disease in children and teenagers without referral for endoscopy
Authors: Van de Vijver Els , Schreuder Andrea Bertilde , Cnossen Wybrich Riemke , Muller Kobold Anna Caecilia , van Rheenen Patrick Ferry 
Published: September 2012

BackgroundUp to 70% of children and teenagers referred to a paediatric gastroenterology centre with suspected inflammatory bowel disease (IBD) do not have the disease.ObjectiveTo evaluate whether faecal calprotectin as an ‘add-on test’ improves the specificity of the clinical case definition for suspected IBD in a general paediatric practice.DesignA prospective diagnostic accuracy study.SettingSix outpatient clinics for general paediatrics and one tertiary care hospital in the Netherlands.Patients117 children and teenagers with a clinical suspicion of IBD.Diagnostic testsFaecal calprotectin was measured (index test) in all patients. Patients with a high index of suspicion on the basis of the paediatrician's global assessment, physical examination and blood results were referred for endoscopy (reference standard). Children and teenagers who were not selected for endoscopy initially were followed for half a year for the appearance of possible additional symptoms (delayed type reference standard).Primary outcomeThe proportion of referred patients with confirmed IBD.ResultsThe mean age of patients was 14 years (range 6–18). A total of 42 (36%) had confirmed IBD. The paediatricians, who were blinded to the faecal calprotectin result, referred 68 children and teenagers for endoscopy. If they had referred only those patients with a positive faecal calprotectin result (>50 μg/g), 54 patients would have undergone endoscopy.LimitationThe study relied on clinical follow-up to detect missed IBD.ConclusionsA diagnostic strategy in general paediatric practice of using a simple clinical case definition for suspected IBD in combination with a positive faecal calprotectin result increases the specificity to detect IBD and reduces the need for referral to a paediatric gastroenterology centre with a very low risk of missing cases.
Efficacy of metronome sound guidance via a phone speaker during dispatcher-assisted compression-only cardiopulmonary resuscitation by an untrained layperson: a randomised controlled simulation study using a manikin
Authors: Park Sang O , Hong Chong Kun , Shin Dong Hyuk , Lee Jun Ho , Hwang Seong Youn 
Published: September 2012

AimUntrained laypersons should perform compression-only cardiopulmonary resuscitation (COCPR) under a dispatcher's guidance, but the quality of the chest compressions may be suboptimal. We hypothesised that providing metronome sounds via a phone speaker may improve the quality of chest compressions during dispatcher-assisted COCPR (DA-COCPR).MethodsUntrained laypersons were allocated to either the metronome sound-guided group (MG), who performed DA-COCPR with metronome sounds (110 ticks/min), or the control group (CG), who performed conventional DA-COCPR. The participants of each group performed DA-COCPR for 4 min using a manikin with Skill-Reporter, and the data regarding chest compression quality were collected.ResultsThe data from 33 cases of DA-COCPR in the MG and 34 cases in the CG were compared. The MG showed a faster compression rate than the CG (111.9 vs 96.7/min; p=0.018). A significantly higher proportion of subjects in the MG performed the DA-COCPR with an accurate chest compression rate (100–120/min) compared with the subjects in the CG (32/33 (97.0%) vs 5/34 (14.7%); p<0.0001). The mean compression depth was not different between the MG and the CG (45.9 vs 46.8 mm; p=0.692). However, a higher proportion of subjects in the MG performed shallow compressions (compression depth <38 mm) compared with subjects in the CG (median % was 69.2 vs 15.7; p=0.035).ConclusionsMetronome sound guidance during DA-COCPR for the untrained bystanders improved the chest compression rates, but was associated more with shallow compressions than the conventional DA-COCPR in a manikin model.
The role of physical examination in diagnosing common causes of vaginitis: a prospective study
Authors: Singh Rameet H , Zenilman Jonathan M , Brown Kathryn M , Madden Tessa , Gaydos Charlotte , Ghanem Khalil G 
Published: September 2012

ObjectiveWe evaluated agreement in diagnoses for bacterial vaginosis (BV),Trichomonas vaginalis(TV) and vulvovaginal candidiasis (VVC) between clinicians examining the patient and performing diagnostic tests versus a clinician with access only to the patient's history and diagnostic findings from self-obtained vaginal swabs (SOVS).DesignWomen presenting with vaginal discharge to a sexually transmitted infections clinic provided SOVS for evaluation and completed the study and qualitative questionnaires. A clinician then obtained a history and performed speculum and bimanual examinations. Participants’ history and diagnostic test results from SOVS were provided to a masked non-examining clinician who rendered independent diagnoses. Overall agreement in diagnoses and κ statistics was calculated.ResultsThe prevalence of infections among the 197 participants was 63.4% (BV), 19% (TV) and 14% (VVC). The per cent agreement between the examining and non-examining clinician for the diagnoses of BV was 68.5%, 90.9% for TV and 91.9% for VVC. Of the 105 women diagnosed with BV by the examining clinician, 34 (32%) were missed by the non-examining clinician. The non-examining clinician missed 13 (48%) of 27 women and 12 (34%) of 35 women treated for VVC and TV, respectively. Four women who all presented with abdominal pain were diagnosed with pelvic inflammatory disease.ConclusionsTests from SOVS and history alone cannot be used to adequately diagnose BV, TV and VVC in women presenting with symptomatic vaginal discharge. Cost benefits from eliminating the speculum examination and using only tests from SOVS may be negated by long-term costs of mistreatment.
FGFR3 Stimulates Stearoyl CoA Desaturase 1 Activity to Promote Bladder Tumor Growth
Authors: Du Xiangnan , Wang Qian-Rena , Chan Emily , Merchant Mark , Liu Jinfeng , French Dorothy , Ashkenazi Avi , Qing Jing 
Published: September 2012

Abstract
Fibroblast growth factor receptor 3 (FGFR3) belongs to a family of receptor tyrosine kinases that control cell proliferation, differentiation, and survival. Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. Through transcriptional profiling of bladder carcinoma cells subjected to short hairpin RNA knockdown of FGFR3, we identified a gene-signature linking FGFR3 signaling with de novo sterol and lipid biosynthesis and metabolism. We found that FGFR3 signaling promotes the cleavage and activation of the master transcriptional regulator of lipogenesis, sterol regulatory element-binding protein 1(SREBP1/SREBF1), in a PI3K-mTORC1-dependent fashion. In turn, SREBP1 regulates the expression of key lipogenic enzymes, including stearoyl CoA desaturase 1 (SCD1/SCD). SCD1 is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids and is crucial for lipid homeostasis. In human bladder cancer cell lines expressing constitutively active FGFR3, knockdown of SCD1 by siRNA markedly attenuated cell-cycle progression, reduced proliferation, and induced apoptosis. Furthermore, inducible knockdown of SCD1 in a bladder cancer xenograft model substantially inhibited tumor progression. Pharmacologic inhibition of SCD1 blocked fatty acid desaturation and also exerted antitumor activity in vitro and in vivo. Together, these findings reveal a previously unrecognized role of FGFR3 in regulating lipid metabolism to maintain tumor growth and survival, and also identify SCD1 as a potential therapeutic target for FGFR3-driven bladder cancer. Cancer Res; 72(22); 5843–55. ©2012 AACR.
Loss of SNAIL Regulated miR-128-2 on Chromosome 3p22.3 Targets Multiple Stem Cell Factors to Promote Transformation of Mammary Epithelial Cells
Authors: Qian PengXu , Banerjee Arindam , Wu Zheng-Sheng , Zhang Xiao , Wang Hong , Pandey Vijay , Zhang Wei-Jie , Lv Xue-Fei , Tan Sheng , Lobie Peter E. , Zhu Tao 
Published: September 2012

AbstractA discontinuous pattern of LOH at chromosome 3p has been reported in 87% of primary breast cancers. Despite the identification of several tumor suppressor genes in this region, there has yet to be a detailed analysis of noncoding RNAs including miRNAs in this region. In this study, we identified 16 aberrant miRNAs in this region and determined several that are frequently lost or amplified in breast cancer. miR-128-2 was the most commonly deleted miRNA. Embedded in the intron of the ARPP21 gene at chromosome 3p22.3, miR-128-2 was frequently downregulated along with ARPP21 in breast cancer, where it was negatively associated with clinicopathologic characteristics and survival outcome. Forced expression of miR-128 impeded several oncogenic traits of mammary carcinoma cells, whereas depleting miR-128-2 expression was sufficient for oncogenic transformation and stem cell-like behaviors in immortalized nontumorigenic mammary epithelial cells, both in vitro and in vivo. miR-128-2 silencing enabled transforming capacity partly by derepressing a cohort of direct targets (BMI1, CSF1, KLF4, LIN28A, NANOG, and SNAIL), which together acted to stimulate the PI3K/AKT and STAT3 signaling pathways. We also found that miR-128-2 was directly downregulated by SNAIL and repressed by TGF-β signaling, adding 2 additional negative feedback loops to this network. In summary, we have identified a novel TGF-β/SNAIL/miR-128 axis that provides a new avenue to understand the basis for oncogenic transformation of mammary epithelial cells. Cancer Res; 72(22); 6036–50. ©2012 AACR.
DDX31 Regulates the p53-HDM2 Pathway and rRNA Gene Transcription through Its Interaction with NPM1 in Renal Cell Carcinomas
Authors: Fukawa Tomoya , Ono Masaya , Matsuo Taisuke , Uehara Hisanori , Miki Tsuneharu , Nakamura Yusuke , Kanayama Hiro-omi , Katagiri Toyomasa 
Published: September 2012

Abstract
Studies of renal cell carcinoma (RCC) have led to the development of new molecular-targeted drugs but its oncogenic origins remain poorly understood. Here, we report the identification and critical roles in renal carcinogenesis for DDX31, a novel nucleolar protein upregulated in the vast majority of human RCC. Immunohistochemical overexpression of DDX31 was an independent prognostic factor for patients with RCC. RNA interference (RNAi)-mediated attenuation of DDX31 in RCC cells significantly suppressed outgrowth, whereas ectopic DDX31 overexpression in human 293 kidney cells drove their proliferation. Endogenous DDX31 interacted and colocalized with nucleophosmin (NPM1) in the nucleoli of RCC cells, and attenuation of DDX31 or NPM1 expression decreased pre-ribosomal RNA biogenesis. Notably, in DDX31-attenuated cells, NPM1 was translocated from nucleoli to the nucleoplasm or cytoplasm where it bound to HDM2. As a result, HDM2 binding to p53 was reduced, causing p53 stablization with concomitant G1 phase cell-cycle arrest and apoptosis. Taken together, our findings define a mechanism through which control of the DDX31–NPM1 complex is likely to play critical roles in renal carcinogenesis. Cancer Res; 72(22); 5867–77. ©2012 AACR.
Antibody-Dependent Cell-Mediated Cytotoxicity Overcomes NK Cell Resistance in MLL-Rearranged Leukemia Expressing Inhibitory KIR Ligands but Not Activating Ligands
Authors: Chan Wing Keung , Kung Sutherland May , Li Ying , Zalevsky Jonathan , Schell Sarah , Leung Wing 
Published: September 2012

Abstract
Purpose: Leukemias with MLL gene rearrangement are associated with a poor prognosis. Natural killer (NK) cell therapy is a potential treatment, but leukemia cells may be resistant. Here, we sought to determine the susceptibility of MLL-rearranged leukemia cells to NK cell lysis and to develop a novel immunotherapeutic approach to optimize NK cell therapy, including the use of an antibody against leukemia-associated antigen and the elimination of killer-cell immunoglobulin-like receptor (KIR)–mediated inhibition.
Experimental Design: Three MLL-rearranged leukemia cell lines (RS4;11, SEM, and MV4-11) and primary leukemia blasts were assessed for surface phenotype and susceptibility to NK cell lysis with or without antibodies against CD19 (XmAb5574), CD33 (lintuzumab), or KIR ligands.
Results: All three cell lines were resistant to NK cell lysis, had some inhibitory KIR ligands and protease inhibitor-9, and expressed low levels of NKG2D activating ligands and adhesion molecules. After treatment with XmAb5574 or lintuzumab, MLL-rearranged leukemia cells were efficiently killed by NK cells. The addition of pan–major histocompatibility complex class I antibody, which blocked inhibitory KIR-HLA interaction, further augmented degranulation in all three KIR2DL1, KIR2DL2/3, and KIR3DL1 subsets of NK cells based on the rule of missing-self recognition. A mouse model showed a decreased rate of leukemia progression in vivo as monitored by bioluminescence imaging and longer survival after antibody treatment.
Conclusion: Our data support the use of a triple immunotherapy approach, including an antibody directed against tumor-associated antigen, KIR-mismatched NK cell transplantation, and inhibitory KIR blockade, for the treatment of NK cell–resistant MLL-rearranged leukemias. Clin Cancer Res; 18(22); 6296–305. ©2012 AACR.
Using Pharmacokinetic and Pharmacodynamic Data in Early Decision Making Regarding Drug Development: A Phase I Clinical Trial Evaluating Tyrosine Kinase Inhibitor, AEE788
Authors: Baselga José , Mita Alain C. , Schöffski Patrick , Dumez Herlinde , Rojo Frederico , Tabernero Josep , DiLea Clifford , Mietlowski William , Low Christie , Huang Jerry , Dugan Margaret , Parker Kathryn , Walk Eric , van Oosterom Allan , Martinelli Erika , Takimoto Chris H. 
Published: September 2012

Abstract
Purpose: In this first-in-human study of AEE788, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), HER-2, and VEGFR-2, a comprehensive pharmacodynamic program was implemented in addition to the evaluation of safety, pharmacokinetics, and preliminary efficacy of AEE788 in cancer patients.
Experimental design: Patients with advanced, solid tumors received escalating doses of oral AEE788 once daily. Primary endpoints were to determine dose-limiting toxicities (DLTs) and maximum-tolerated dose (MTD). A nonlinear model (Emax model) was used to describe the relationship between AEE788 exposure and target-pathway modulation in skin and tumor tissues.
Results: Overall, 111 patients were treated (25 to 550 mg/day). DLTs included rash and diarrhea; MTD was 450 mg/day. Effects on biomarkers correlated to serum AEE788 concentrations. The concentration at 50% inhibition (IC50) for EGFR in skin (0.033 μmol/L) and tumor (0.0125 μmol/L) were similar to IC50in vitro suggesting skin may be surrogate tissue for estimating tumor EGFR inhibition. No inhibition of p-MAPK and Ki67 was observed in skin vessels at ≤MTD. Hence, AEE788 inhibited EGFR, but not VEGFR, at doses ≤MTD. A total of 16 of 96 evaluable patients showed a &gt;10% shrinkage of tumor size; one partial response was observed.
Conclusion: Our pharmacodynamic-based study showed effective inhibition of EGFR, but not of VEGFR at tolerable AEE788 doses. Emax modeling integrated with biomarker data effectively guided real-time decision making in the early development of AEE788. Despite clinical activity, target inhibition of only EGFR led to discontinuation of further AEE788 development. Clin Cancer Res; 18(22); 6364–72. ©2012 AACR.
Model T Muscle CARs Can Treat Brain Tumors
Authors: Johnson Laura A. 
Published: September 2012

Abstract
Despite standard treatment with resection, radiation, and chemotherapy, glioblastoma remains a deadly disease with a dismal prognosis. Redirecting patient T cells to target the glioblastoma-associated antigen, IL13Rα2, offers a promising translational immunotherapy with the potential to make a meaningful impact for patients with this disease. Clin Cancer Res; 18(21); 5834–6. ©2012 AACR.
A Multiscale Model for the Modulation and Rectification of the ITCZ
Authors: Biello Joseph A. , Majda Andrew J. 
Published: September 2012

Abstract
The authors introduce the modulation of the ITCZ equations (M-ITCZ), which describes the multiscale dynamics of the ITCZ on diurnal to monthly time scales in which mesoscale convectively coupled Rossby waves in the ITCZ are modulated by a large-scale gravity wave that is also generated by convection. Westward-propagating disturbances are observed to cause ITCZ breakup over the course of a few days, and the M-ITCZ meso-/planetary-scale coupled waves provide a mechanism for this interaction, thereby providing a framework to study the modulation and rectification of the Hadley circulation over long zonal length scales in the ITCZ.
The authors consider examples of zonally symmetric heating profiles in the M-ITCZ system and generate a Hadley circulation consistent with the observed winds. Zonally localized heating creates a wind response throughout the tropics that is carried by a pair of zonally propagating gravity bores driving mean easterlies at the base and mean westerlies at the top of the troposphere. The bores carry low-temperature and upward velocity perturbations to the west of the heating and high-temperature and downward velocity perturbations to the east, making the westward-propagating branch favorable to convective triggering and the eastward-propagating branch favorable to convective suppression.
The mesoscale dynamics of the M-ITCZ describe convectively forced, nonlinear Rossby waves propagating in the zonal winds created by the planetary-scale gravity wave. The authors suggest that convective coupling slows the westward-propagating gravity wave, thereby creating a coupled gravity–Rossby wave that is similar to the westward-propagating disturbances seen in the ITCZ.
A Comparison of the Water Budgets between Clouds from AMMA and TWP-ICE
Authors: Zeng Xiping , Tao Wei-Kuo , Powell Scott W. , Houze Robert A. , Ciesielski Paul , Guy Nick , Pierce Harold , Matsui Toshihisa 
Published: September 2012

AbstractTwo field campaigns, the African Monsoon Multidisciplinary Analysis (AMMA) and the Tropical Warm Pool–International Cloud Experiment (TWP-ICE), took place in 2006 near Niamey, Niger, and Darwin, Northern Territory, Australia, providing extensive observations of mesoscale convective systems (MCSs) near a desert and a tropical coast, respectively. Under the constraint of their observations, three-dimensional cloud-resolving model simulations are carried out and presented in this paper to replicate the basic characteristics of the observed MCSs. All of the modeled MCSs exhibit a distinct structure having deep convective clouds accompanied by stratiform and anvil clouds. In contrast to the approximately 100-km-scale MCSs observed in TWP-ICE, the MCSs in AMMA have been successfully simulated with a scale of about 400 km.These modeled AMMA and TWP-ICE MCSs offer an opportunity to understand the structure and mechanism of MCSs. Comparing the water budgets between AMMA and TWP-ICE MCSs suggests that TWP-ICE convective clouds have stronger ascent while the mesoscale ascent outside convective clouds in AMMA is stronger. A case comparison, with the aid of sensitivity experiments, also suggests that vertical wind shear and ice crystal (or dust aerosol) concentration can significantly impact stratiform and anvil clouds (e.g., their areas) in MCSs. In addition, the obtained water budgets quantitatively describe the transport of water between convective, stratiform, and anvil regions as well as water sources/sinks from microphysical processes, providing information that can be used to help determine parameters in the convective and cloud parameterizations in general circulation models (GCMs).
Climate Impacts of Land-Cover and Land-Use Changes in Tropical Islands under Conditions of Global Climate Change
Authors: Comarazamy Daniel E. , González Jorge E. , Luvall Jeffrey C. , Rickman Douglas L. , Bornstein Robert D. 
Published: September 2012

AbstractLand-cover and land-use (LCLU) changes have significant climate impacts in tropical coastal regions with the added complexity of occurring within the context of a warming climate. The individual and combined effects of these two factors in tropical islands are investigated by use of an integrated mesoscale atmospheric modeling approach, taking the northeastern region of Puerto Rico as the test case. To achieve this goal, an ensemble of climate simulations is performed, combining two LCLU and global warming scenarios. Reconstructed agricultural maps and sea surface temperatures form the past (1955–59) scenario, while the present (2000–04) scenario is supported with high-resolution remote sensing LCLU data. Here, the authors show that LCLU changes produced the largest near-surface (2-m AGL) air temperature differences over heavily urbanized regions and that these changes do not penetrate the boundary layer. The influence of the global warming signal induces a positive inland gradient of maximum temperature, possibly because of increased trade winds in the present climatology. These increased winds also generate convergence zones and convection that transport heat and moisture into the boundary layer. In terms of minimum temperatures, the global warming signal induces temperature increases along the coastal plains and inland lowlands.
Seasonality of Airmass Pathways to Coastal Antarctica: Ramifications for Interpreting High-Resolution Ice Core Records
Authors: Sinclair Kate E. , Bertler Nancy A. N. , Trompetter W. J. , Baisden W. T. 
Published: September 2012

AbstractUnderstanding airmass pathways is critical for ice core interpretation, and the ability to determine the broadscale characteristics and seasonality of synoptic-scale flow using paleoclimate records offers great potential to improve the understanding of past atmospheric circulation. The dominant airmass pathways to a coastal Antarctic ice core site at the Whitehall Glacier in the Ross Sea are modeled using snowfall and high-resolution stable isotope data between 1979 and 2006, combined with back trajectories produced from both NCEP–NCAR and ECMWF Interim Re-Analysis (ERA-Interim) data. Back trajectories generated from both datasets produce comparable results. They show that high snowfall is associated with cyclonic airflow in the Ross Sea with a strong meridional component along the western Ross Sea coast. Over a 28-yr time frame, trajectories also reveal a clear distinction between flow paths associated with above- and below-average annual temperatures (high and low δD) in the ice core record. In cold months (low δD), when there is a strengthened trough of low pressure around the continent, synoptically driven incursions of marine air across West Antarctica and trajectories originating from coastal East Antarctica are dominant. Conversely, in warmer months (high δD), airmass pathways are centered over the Ross Sea and the adjacent Southern Ocean. These trajectories are slower moving and are expected to draw marine moisture from high-latitude seasonally open oceans.