bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Fat, High-Calorie Diet Promotes Early Pancreatic Neoplasia in the Conditional KrasG12D Mouse Model
Authors: Dawson David W. , Hertzer Kathleen , Moro Aune , Donald Graham , Chang Hui-Hua , Go Vay Liang , Pandol Steven J. , Lugea Aurelia , Gukovskaya Anna S. , Li Gang , Hines Oscar J. , Rozengurt Enrique , Eibl Guido 
Published: August 2013

Abstract
There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, for example, weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a high-fat, high-calorie diet (HFCD; ∼4,535 kcal/kg; 40% of calories from fats) or control diet (∼3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared with control animals, mice fed with the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin-like growth factor I (IGF-I). The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results show that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemopreventive strategies targeting obesity-associated pancreatic cancer development. Cancer Prev Res; 6(10); 1064–73. ©2013 AACR.
Acacetin InhibitsIn VitroandIn VivoAngiogenesis and Downregulates Stat Signaling and VEGF Expression
Authors: Bhat Tariq A. , Nambiar Dhanya , Tailor Dhanir , Pal Arttatrana , Agarwal Rajesh , Singh Rana P. 
Published: August 2013

AbstractAngiogenesis is an effective target in cancer control. The antiangiogenic efficacy and associated mechanisms of acacetin, a plant flavone, are poorly known. In the present study, acacetin inhibited growth and survival (up to 92%; P &lt; 0.001), and capillary-like tube formation on Matrigel (up to 98%; P &lt; 0.001) by human umbilical vein endothelial cells (HUVEC) in regular condition, as well as VEGF-induced and tumor cells conditioned medium–stimulated growth conditions. It caused retraction and disintegration of preformed capillary networks (up to 91%; P &lt; 0.001). HUVEC migration and invasion were suppressed by 68% to 100% (P &lt; 0.001). Acacetin inhibited Stat-1 (Tyr701) and Stat-3 (Tyr705) phosphorylation, and downregulated proangiogenic factors including VEGF, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and basic fibroblast growth factor (bFGF) in HUVEC. It also suppressed nuclear localization of pStat-3 (Tyr705). Acacetin strongly inhibited capillary sprouting and networking from rat aortic rings and fertilized chicken egg chorioallantoic membrane (CAM; ∼71%; P &lt; 0.001). Furthermore, it suppressed angiogenesis in Matrigel plugs implanted in Swiss albino mice. Acacetin also inhibited tyrosine phosphorylation of Stat-1 and -3, and expression of VEGF in cancer cells. Overall, acacetin inhibits Stat signaling and suppresses angiogenesis in vitro, ex vivo, and in vivo, and therefore, it could be a potential agent to inhibit tumor angiogenesis and growth. Cancer Prev Res; 6(10); 1128–39. ©2013 AACR.
Outcomes After Primary Transcatheter Therapy in Infants and Young Children With Severe Bilateral Peripheral Pulmonary Artery Stenosis
Authors: Cunningham Jonathan W. , McElhinney Doff B. , Gauvreau Kimberlee , Bergersen Lisa , Lacro Ronald V. , Marshall Audrey C. , Smoot Leslie , Lock James E. 
Published: August 2013

Background—
Angioplasty and stent implantation have become accepted therapies for isolated peripheral pulmonary stenosis, and have been shown to increase vessel diameter and reduce right ventricular (RV) pressure acutely in patients with pulmonary artery (PA) stenosis. The purpose of this study was to assess long-term outcomes after primary transcatheter therapy for peripheral pulmonary stenosis.

Methods and Results—

We studied 69 patients who underwent primary transcatheter intervention for severe isolated peripheral pulmonary stenosis at ≤5 years of age. Genetic/syndromic diagnoses included Williams syndrome (n=23), non-Williams familial arteriopathy (n=12), and Alagille syndrome (n=3). At the initial PA intervention, median RV:aortic pressure ratio decreased from 1.00 to 0.88 (median decrease, 0.18;
P
<0.001). Patients with a higher preintervention RV:aortic pressure ratio had a greater reduction (
P
<0.001). During follow-up (median, 8.5 years), 10 patients died, 5 from complications of PA catheterization (all before 1998). Thirteen patients underwent surgical PA intervention, most within 1 year and along with repair of supravalvar aortic stenosis. Freedom from any PA reintervention was 38±6% at 1 year and 22±6% at 5 years. The median RV:aortic pressure ratio decreased from 1.0 at baseline to 0.53 at the most recent catheterization (
P
<0.001), and 82% of patients with available clinical follow-up were asymptomatic.

Conclusions—
Transcatheter therapy for infants with severe peripheral pulmonary stenosis has become safer, regardless of genetic condition. Coupled with reintervention and surgical relief in selected cases, RV:aortic pressure ratios decrease substantially and most patients are asymptomatic at late follow-up.
Pre-modern Chinese Sources in the National History of Brunei: The Case of Poli
Authors: Kurz Johannes L. 
Published: August 2013

Abstract
The article deals with the appropriation of pre-modern Chinese sources by R. Nicholl and others for the national history of Brunei. It provides an analysis of the relevant sources and argues that Poli, a country described in the Chinese texts, was not a precursor of Brunei.
Cultivating Plantations and Subjects in East Timor: A Genealogy
Authors: Shepherd Christopher J. , McWilliam Andrew 
Published: August 2013

Abstract
This article traces the emergence and institutionalization of plantation systems and cash crops in East Timor over two centuries. It examines the continuities, ruptures and shifting politics across successive plantation styles and political regimes, from Portuguese colonialism through Indonesian occupation to post-colonial independence. In following plantation agriculture from its origins to the present, the article explores how plantation subjects have been formed successively through racial discourse, repressive discipline, technical authority and neoliberal market policies. We argue that plantation politics have been instrumental in reproducing the class distinctions that remain evident in East Timor today.
Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates
Authors: Tazawa Hirofumi , Irei Toshimitsu , Tanaka Yuka , Igarashi Yuka , Tashiro Hirotaka , Ohdan Hideki 
Published: August 2013

Key PointsAdministration of anti-mouse CD1d blocking mAb prior to A-RBC immunization abolished IL-5 production and anti-A Ab production in mice. In human peripheral blood mononuclear cell–NOD/SCID mice, administration of anti-human CD1d mAb prior to A-RBC immunization completely inhibited anti-A Ab production.
Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia
Authors: Yang Wen-Chi , Tsai Wan-Chi , Lin Pai-Mei , Yang Ming-Yu , Liu Yi-Chang , Chang Chao-Sung , Yu Wen-Hui , Lin Sheng-Fung 
Published: August 2013

Abstract

Background
The relevance of recurrent molecular abnormalities in cytogenetically normal (CN) acute myeloid leukemia (AML) was recently acknowledged by the inclusion of molecular markers such as NPM1, FLT3, and CEBPA as a complement to cytogenetic information within both the World Health Organization and the European Leukemia Net classifications. Mitochondrial metabolism is different in cancer and normal cells. A novel cytosolic type 2-hydroxybutyrate dehydrogenase, BDH2, originally named DHRS6, plays a physiological role in the cytosolic utilization of ketone bodies, which can subsequently enter mitochondria and the tricarboxylic acid cycle. Moreover, BDH2 catalyzes the production of 2, 3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis.

Results
We observed that BDH2 expression is an independent poor prognostic factor for CN-AML, with an anti-apoptotic role. Patients with high BDH2 expression have relatively shorter overall survival (P = 0.007) and a low complete response rate (P = 0.032). BDH2-knockdown (BDH2-KD) in THP1 and HL60 cells increased the apoptosis rate under reactive oxygen species stimulation. Decrease inducible survivin, a member of the inhibitors of apoptosis family, but not members of the Bcl-2 family, induced apoptosis via a caspase-3-independent pathway upon BDH2-KD.

Conclusions

BDH2 is a novel independent poor prognostic marker for CN-AML, with the role of anti-apoptosis, through surviving.
Genetic diversity and population structure of rice landraces from Eastern and North Eastern States of India
Authors: Das Basabdatta , Sengupta Samik , Parida Swarup Kumar , Roy Bipasha , Ghosh Mrityunjay , Prasad Manoj , Ghose Tapas Kumar 
Published: August 2013

Abstract

Background
Adaptations to different habitats across the globe and consequent genetic variation within rice have resulted in more than 120,000 diverse accessions including landraces, which are vital genetic resources for agronomic and quality traits. In India the rice landraces of the states West Bengal, Assam, Mizoram, Manipur and Nagaland are worthy candidates for genetic assessment. Keeping the above in view, the present study was conducted with the aim to (i) calculate the genetic distances among the accessions of 83 landraces collected from these states along with 8 check accessions (total 91 accessions) using 23 previously mapped SSR markers and (ii) examine the population structure among the accessions using model-based clustering approach.

Results
Among the 91 accessions, 182 alleles were identified which included 51 rare and 27 null alleles. The average PIC value was 0.7467/marker. The non-aromatic landraces from West Bengal was most diverse with 154 alleles and an average PIC value of 0.8005/marker, followed by the aromatic landraces from West Bengal with 118 alleles and an average PIC value of 0.6524/marker, while the landraces from North East ranked third with 113 alleles and an average PIC value of 0.5745/marker. In the dendrogram distinct clusters consisting of predominantly aromatic landraces and predominantly North East Indian landraces were observed. The non-aromatic landraces from West Bengal were interspersed within these two clusters. The accessions were moderately structured, showing four sub-populations (A-D) with an Fst value of 0.398, 0.364, 0.206 and 0.281, respectively. The assigned clustering of accessions was well in agreement in both distance-based and model-based approaches.

Conclusions
Each of the accessions could be identified unequivocally by the SSR profiles. Genetically the non aromatic landraces from West Bengal were most diverse followed by the aromatic landraces from the same state. The North Eastern accessions ranked third. Further, grouping of accessions based on their agronomic traits may serve as a resource for future studies, leading to the improvement of rice. Moreover in-situ preservation of the landraces is also a means of protection of biodiversity and cultural heritage.
DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice
Authors: Cao Jun , Jin Yiqi , Li Wei , Zhang Bin , He Yang , Liu Hongqiang , Xia Ning , Wei Huafeng , Yan Jian 
Published: August 2013

AbstractBackgroundAlthough DNA vaccine holds a great potential for cancer immunotherapy, effective long-lasting antitumoral immunity sufficient to induce durable responses in cancer patients remains to be achieved. Considering the pivotal role of dendritic cells (DC) in the antigen processing and presentation, we prepared DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from NLDC-145 antibody specific for DC-restricted surface molecule DEC-205 (scFvNLDC-145), and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models.ResultsIn vivo targeting assay demonstrated that scFvNLDC-145specifically delivered DNA vaccine-encoded antigen to DC. Compared with untargeted HER2/neu DNA vaccines, vaccination with scFvNLDC-145-HER2/neu markedly promoted the HER2/neu-specific cellular and humoral immune responses with long-lasting immune memory, resulting in effective protection against challenge of HER2/neu-positive D2F2/E2 breast tumor while ineffective in parental HER2/neu-negative D2F2 breast tumor. More importantly, in combination with temporary depletion of regulatory T cells (Treg) by low-dose cyclophosphamide, vaccination with scFvNLDC-145-HER2/neu induced the regression of established D2F2/E2 breast tumor and significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice.ConclusionOur findings demonstrate that DC-targeted DNA vaccines for in vivo direct delivery of tumor antigens to DC could induce potent antigen-specific cellular and humoral immune responses and, if additional combination with systemic Treg depletion, was able to elicit an impressively therapeutic antitumoral activity, providing a rationale for further development of this approach for cancer treatment.
The development of chronic cough in children following presentation to a tertiary paediatric emergency department with acute respiratory illness: study protocol for a prospective cohort study
Authors: Drescher Benjamin J , Chang Anne B , Phillips Natalie , Acworth Jason , Marchant Julie , Sloots Theo P , David Michael , O’Grady Kerry-Ann F 
Published: August 2013

Abstract

Background
Acute respiratory illness, a leading cause of cough in children, accounts for a substantial proportion of childhood morbidity and mortality worldwide. In some children acute cough progresses to chronic cough (>4 weeks duration), impacting on morbidity and decreasing quality of life. Despite the importance of chronic cough as a cause of substantial childhood morbidity and associated economic, family and social costs, data on the prevalence, predictors, aetiology and natural history of the symptom are scarce. This study aims to comprehensively describe the epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children presenting to a tertiary paediatric emergency department.

Methods/design
A prospective cohort study of children aged <15 years attending the Royal Children’s Hospital Emergency Department, Brisbane, for a respiratory illness that includes parent reported cough (wet or dry) as a symptom. The primary objective is to determine the prevalence and predictors of chronic cough (≥4 weeks duration) post presentation with acute respiratory illness. Demographic, epidemiological, risk factor, microbiological and clinical data are completed at enrolment. Subjects complete daily cough dairies and weekly follow-up contacts for 28(±3) days to ascertain cough persistence. Children who continue to cough for 28 days post enrolment are referred to a paediatric respiratory physician for review. Primary analysis will be the proportion of children with persistent cough at day 28(±3). Multivariate analyses will be performed to evaluate variables independently associated with chronic cough at day 28(±3).

Discussion
Our protocol will be the first to comprehensively describe the natural history, epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children. The results will contribute to studies leading to the development of evidence-based clinical guidelines to improve the early detection and management of chronic cough in children during and after acute respiratory illness.
Symptoms, signs and nerve conduction velocities in patients with suspected carpal tunnel syndrome
Authors: Ntani Georgia , Palmer Keith T , Linaker Cathy , Harris E Clare , Van der Star Richard , Cooper Cyrus , Coggon David 
Published: August 2013

Abstract

Background
To inform the clinical management of patients with suspected carpal tunnel syndrome (CTS) and case definition for CTS in epidemiological research, we explored the relation of symptoms and signs to sensory nerve conduction (SNC) measurements.

Methods
Patients aged 20–64 years who were referred to a neurophysiology service for investigation of suspected CTS, completed a symptom questionnaire (including hand diagrams) and physical examination (including Tinel’s and Phalen’s tests). Differences in SNC velocity between the little and index finger were compared according to the anatomical distribution of symptoms in the hand and findings on physical examination.

Results
Analysis was based on 1806 hands in 908 patients (response rate 73%). In hands with numbness or tingling but negative on both Tinel’s and Phalen’s tests, the mean difference in SNC velocities was no higher than in hands with no numbness or tingling. The largest differences in SNC velocities occurred in hands with extensive numbness or tingling in the median nerve sensory distribution and both Tinel’s and Phalen’s tests positive (mean 13.8, 95% confidence interval (CI) 12.6-15.0 m/s). Hand pain and thumb weakness were unrelated to SNC velocity.

Conclusions
Our findings suggest that in the absence of other objective evidence of median nerve dysfunction, there is little value in referring patients of working age with suspected CTS for nerve conduction studies if they are negative on both Tinel’s and Phalen’s tests. Alternative case definitions for CTS in epidemiological research are proposed according to the extent of diagnostic information available and the relative importance of sensitivity and specificity.
The relationship between baseline nutritional status with subsequent parenteral nutrition and clinical outcomes in cancer patients undergoing hyperthermic intraperitoneal chemotherapy
Authors: Vashi Pankaj G , Gupta Digant , Lammersfeld Carolyn A , Braun Donald P , Popiel Brenten , Misra Subhasis , Brown Komen C 
Published: August 2013

Abstract

Background
The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for selected patients with peritoneal carcinomatosis. This retrospective study investigated the relationship between baseline nutritional assessment with subsequent parenteral nutritional (PN) and clinical outcomes in cancer patients undergoing CRS and HIPEC.

Methods
A consecutive series of 60 patients undergoing CRS and HIPEC at our institution between January 2009 and May 2011. Subjective Global Assessment (SGA) was used to assess nutritional status. Patients were classified preoperatively as: well nourished (SGA-A), mildly-moderately malnourished (SGA-B), and severely malnourished (SGA-C). For PN, patients were divided into 2 groups: those who received PN (PN+) and those who did not receive PN (PN-). The primary outcomes of interest were length of stay (LOS), postoperative complications, ECOG performance status (PS) and survival. LOS was calculated as the number of days in the hospital post surgery. Performance status was measured on a scale of 0-4. Survival was calculated from the date of first visit to the date of death/last contact.

Results
Of 60 patients, 19 were males and 41 females. The mean age at presentation was 50.3 years. The most common cancer types were colorectal (n = 24) and gynecologic (n = 19) with the majority of patients (n = 47) treated previously before coming to our institution. 33 patients were SGA-A, 22 SGA-B and 5 SGA-C prior to surgery. Of a total of 60 patients, 31 received PN. Mean LOS for the entire cohort was 16.2 days (SD = 9.8). Mean LOS for preoperative SGA-A, SGA-B and SGA-C were 15.0, 15.2 and 27.8 days respectively (ANOVA p = 0.02). Overall incidence of complications was 26.7% (16/60). Complications were recorded in 9 of 33 (27.3%) preoperative SGA-A patients and 7 of 27 (25.9%) SGA-B + C patients (p = 0.91). The median overall survival was 17.5 months (95% CI = 13.0 to 22.1 months). Median survival for preoperative SGA-A and SGA-B + C cohorts was 22.4 and 10.4 months respectively (p = 0.006).

Conclusions
The preoperative SGA predicts LOS and survival in cancer patients undergoing HIPEC. Future randomized clinical trials in this patient population should investigate the systematic provision of PN to all malnourished patients in the preoperative period for a minimum of 7-10 days with the continuation of PN in the postoperative period.
The identification of novel targets of miR-16 and characterization of their biological functions in cancer cells
Authors: Yan Xin , Liang Hongwei , Deng Ting , Zhu Kegan , Zhang Suyang , Wang Nan , Jiang Xueyuan , Wang Xueliang , Liu Rui , Zen Ke , Zhang Chen-Yu , Ba Yi , Chen Xi 
Published: August 2013

Abstract

Background
In eukaryotes, miR-16 is an important microRNA (miRNA) that is involved in numerous biological processes. However, it is not fully understood how miR-16 executes its physiological functions. In the present study, we aimed to identify novel miR-16 targets and study their biological functions.

Methods
Candidate target genes of miR-16 were screened by microarray analysis of mRNA levels in several cancer cell lines with enhanced miR-16. Three bioinformatics algorithms, including TargetScan, PicTar, and miRanda, were used in combination to calculate the miR-16 targets. The expression levels of miR-16 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. The effect of miR-16 and target gene on cell viability was evaluated using MTT assays. The effects of miR-16 and target gene on apoptosis and cell cycle distribution were evaluated by flow cytometry analysis.

Results
By overexpressing miR-16 in several cancer cell lines and measuring global mRNA levels using microarray analysis, we identified 27 genes that may be regulated by miR-16. After the bioinformatics filtering process, 18 genes were selected as candidate miR-16 targets. Furthermore, we experimentally validated three of these candidates, MAP7 (microtubule-associated protein 7), PRDM4 (PR domain containing 4) and CDS2 (CDP-diacylglycerol synthase 2), as direct targets of miR-16. Finally, we demonstrated that miR-16 targeting MAP7 played a critical role in regulating proliferation but not apoptosis and cell cycle progression in cancer cells.

Conclusion
In summary, the present study identifies several novel miR-16 targets and illustrates a novel function of miR-16 targeting MAP7 in modulating proliferation in cancer cells.