bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers
Authors: Carotenuto Pietro , Fassan Matteo , Pandolfo Rosantony , Lampis Andrea , Vicentini Caterina , Cascione Luciano , Paulus-Hock Viola , Boulter Luke , Guest Rachel , Quagliata Luca , Hahne Jens Claus , Ridgway Rachel , Jamieson Tam , Athineos Dimitris , Veronese Angelo , Visone Rosa , Murgia Claudio , Ferrari Giulia , Guzzardo Vincenza , Evans Thomas Ronald Jeffry , MacLeod Martin , Feng Gui Ji , Dale Trevor , Negrini Massimo , Forbes Stuart J , Terracciano Luigi , Scarpa Aldo , Patel Tushar , Valeri Nicola , Workman Paul , Sansom Owen , Braconi Chiara 
Published: September 2016

ObjectiveTranscribed-ultraconserved regions (T-UCR) are long non-coding RNAs which are conserved across species and are involved in carcinogenesis. We studied T-UCRs downstream of the Wnt/β-catenin pathway in liver cancer.DesignHypomorphic Apc mice (Apcfl/fl) and thiocetamide (TAA)-treated rats developed Wnt/β-catenin dependent hepatocarcinoma (HCC) and cholangiocarcinoma (CCA), respectively. T-UCR expression was assessed by microarray, real-time PCR and in situ hybridisation.ResultsOverexpression of the T-UCR uc.158− could differentiate Wnt/β-catenin dependent HCC from normal liver and from β-catenin negative diethylnitrosamine (DEN)-induced HCC. uc.158− was overexpressed in human HepG2 versus Huh7 cells in line with activation of the Wnt pathway. In vitro modulation of β-catenin altered uc.158− expression in human malignant hepatocytes. uc.158− expression was increased inCTNNB1-mutated human HCCs compared with non-mutated human HCCs, and in human HCC with nuclear localisation of β-catenin. uc.158− was increased in TAA rat CCA and reduced after treatment with Wnt/β-catenin inhibitors. uc.158− expression was negative in human normal liver and biliary epithelia, while it was increased in human CCA in two different cohorts. Locked nucleic acid-mediated inhibition of uc.158− reduced anchorage cell growth, 3D-spheroid formation and spheroid-based cell migration, and increased apoptosis in HepG2 and SW1 cells. miR-193b was predicted to have binding sites within the uc.158− sequence. Modulation of uc.158− changed miR-193b expression in human malignant hepatocytes. Co-transfection of uc.158− inhibitor and anti-miR-193b rescued the effect of uc.158− inhibition on cell viability.ConclusionsWe showed that uc.158− is activated by the Wnt pathway in liver cancers and drives their growth. Thus, it may represent a promising target for the development of novel therapeutics.
Expression pattern of miR-451 and its targetMIF(macrophage migration inhibitory factor) in colorectal cancer
Authors: Mamoori Afraa , Gopalan Vinod , Lu Cu-Tai , Chua Terence C , Morris David L , Smith Robert Anthony , Lam Alfred K-Y 
Published: September 2016

AimsTo investigate the expression pattern of microRNA-451 (miR-451) in patients with colorectal carcinoma and correlate with the expression of its target geneMIF(macrophage migration inhibitory factor).MethodsMatched cancer and non-cancer fresh frozen tissues were prospectively collected from 70 patients (35 men and 35 women) who underwent resection of colorectal adenocarcinoma. These tissues collected were extracted for miR and complementary DNA conversion. Then, miR-451 expressions in these tissues were measured by quantitative real-time PCR. The expression was correlated with clinical and pathological parameters of these patients. In addition, paraffin blocks of 10 colorectal carcinomas with lowest expression of miR-451 were used for the study of MIF protein expression by immunohistochemistry.ResultsmiR-451 was downregulated in majority of the colorectal cancer tissues when compared with their matched normal tissues (84.3%, n=59/70). Downregulation of miR-451 correlates significantly with presence of coexisting adenoma (91.4%, p=0.025). In addition, persistence of cancer or cancer recurrence after surgery showed significant correlation with downregulation of miR-451 (80% vs 0%; p=0.028). There is no significant correlation between miR-451 expression and age, gender of the patients as well as size, grades, pathological stages, presence of lymphovascular permeation, perineural invasion and microsatellite instability status of the colorectal carcinoma (p>0.05). Majority of the cases (80%) with low expression of miR-451 showed high levels of MIF protein expression confirming the inverse relationship between miR-451 and MIF expressions.ConclusionsThe results showed that miR-451 could play a role in development and progression of colorectal cancer and likely by targetingMIF.
Impact of a child stimulation intervention on early child development in rural Peru: a cluster randomised trial using a reciprocal control design
Authors: Hartinger Stella Maria , Lanata Claudio Franco , Hattendorf Jan , Wolf Jennyfer , Gil Ana Isabel , Obando Mariela Ortiz , Noblega Magaly , Verastegui Hector , Mäusezahl Daniel 
Published: September 2016

ObjectiveStimulation in early childhood can alleviate adverse effects of poverty. In a community-randomised trial, we implemented 2 home-based interventions, each serving as an attention control for the other. One group received an integrated household intervention package (IHIP), whereas the other group received an early child development (ECD) intervention. The primary objective of the study was to evaluate the effect of IHIP on diarrhoea and respiratory infections, the details of which are described elsewhere. Here, we present the impact of the ECD intervention on early childhood development indicators.MethodsIn this non-blinded community-randomised trial, an ECD intervention, adapted from the Peruvian government's National Wawa Wasi ECD programme, was implemented in 25 rural Peruvian Andean communities. We enrolled 534 children aged 6–35 months, from 50 communities randomised 1:1 into ECD and IHIP communities. In ECD communities, trained fieldworkers instructed mothers every 3 weeks over the 12 months study, to stimulate and interact with their children and to use standard programme toys. IHIP communities received an improved stove and hygiene promotion. Using a nationally validated ECD evaluation instrument, all children were assessed at baseline and 12 months later for overall performance on age-specific developmental milestones which fall into 7 developmental domains.FindingsAt baseline, ECD-group and IHIP-group children performed similarly in all domains. After 12 months, data from 258 ECD-group and 251 IHIP-group children could be analysed. The proportion of children scoring above the mean in their specific age group was significantly higher in the ECD group in all domains (range: 12–23%-points higher than IHIP group). We observed the biggest difference in fine motor skills (62% vs 39% scores above the mean, OR: 2.6, 95% CI 1.7 to 3.9).ConclusionsThe home-based ECD intervention effectively improved child development overall across domains and separately by investigated domain. Home-based strategies could be a promising component of poverty alleviation programmes seeking to improve developmental outcomes among rural Peruvian children.Trial registration numberISRCTN28191222; results.
Increase in avoidable hospital admissions after the Great East Japan Earthquake
Authors: Sasabuchi Yusuke , Matsui Hiroki , Yasunaga Hideo , Fushimi Kiyohide 
Published: September 2016

BackgroundThe Great East Japan Earthquake and subsequent tsunami and nuclear disaster on 11 March 2011 had a short-term influence on the increase in emergency department visits and hospital admissions due to various diseases. However, it remains unclear whether the earthquake and tsunami disaster affected the long-term health conditions of people in the affected areas.MethodsUsing a national inpatient database in Japan, we investigated people's ambulatory care sensitive conditions (ACSCs), which are defined as conditions for which effective management and treatment should prevent admission to a hospital. We compared the number of admissions for ACSCs before-quake (July 2010 to February 2011) with after-quake (July 2012 to February 2013) periods in the disaster area compared with other areas using a difference-in-differences design. Linear regression models with the interaction between periods and areas were used to estimate the impact of the earthquake on admissions for ACSCs.ResultsNo significant difference in difference was seen in preventable ACSCs (where immunisation and other interventions can prevent illness) or chronic ACSCs (where effective care can prevent flare-ups), while acute ACSCs (where early intervention can prevent more serious progression) increased significantly (3.3 admissions per 100 000 population; 95% CI 0.4 to 6.3; p=0.028).ConclusionsPreventable and chronic ACSCs may have increased just after the earthquake and then immediately decreased. However, avoidable admissions due to acute ACSCs remained high in the long term after the earthquake and tsunami disaster.
One-year effects of glucocorticoids on bone density: a meta-analysis in cohorts on high and low-dose therapy
Authors: Lems Willem F , Baak Merel M E , van Tuyl Lilian H D , Lodder Mariëtte C , Dijkmans Ben A C , Boers Maarten 
Published: September 2016

BackgroundBone loss during glucocorticoid (GC) therapy is poorly quantified.ObjectiveQuantification of bone loss in GC-treated patients with chronic inflammatory diseases (CID; low dose) and transplants (high dose).MethodsMeta-analysis of cohorts: PubMed, Cochrane, EMBASE and bibliographic searches (1995–2012). Eligible studies prospectively included GC-treated patients with two dual X-ray absorptiometry measurements of spine or hip over a period of at least 12 months. Only supplementation with calcium or vitamin D3 was allowed. 5602 titles yielded 285 articles: 51 study arms in CID (N=1565), 18 study arms in transplantation (N=571). Prednisone-equivalent GC doses and inverse variance weighted mean bone changes were used in a random effects model.ResultsIn CID, the mean GC dose was 8.7 mg/day (range 1.2–16.4). The mean 1-year bone loss in the lumbar spine was −1.7% (95% CI –2.2% to –1.2%); in the femoral neck: –1.3 (–1.8 to –0.7). In transplantation, the mean GC dose was 18.9 mg/day (range 6.0–52.7). Bone loss in the lumbar spine was −3.6% (–5.2% to –2.0%); in the femoral neck: –3.1% (–5.1% to –1.1%). Within the two groups, bone loss was not related to GC dose.ConclusionIn CID, GC-related bone loss appears limited and manageable if current anti-osteoporotic strategies are fully implemented. In transplantation, and probably also other high-dose settings, bone loss is considerable and represents unmet need. The heterogeneity probably reflects the important influence of other factors, most notably the underlying disease and the efficacy of GC treatment.
A Fault-Tolerant Deflection Routing for Network-on-Chip
Authors: Zhou Xiaofeng , Liu Lu , Zhu Zhangming 
Published: September 2016

Network-on-Chip (NoC) has become a promising design methodology for the modern on-chip communication infrastructure of many-core system. To guarantee the reliability of traffic, effective fault-tolerant scheme is critical to NoC systems. In this paper, we propose a fault-tolerant deflection routing (FTDR) to address faults on links and router by redundancy technique. The proposed FTDR employs backup links and a redundant fault-tolerant unit (FTU) at router-level to sustain the traffic reliability of NoC. Experimental results show that the proposed FTDR yields an improvement of routing performance and fault-tolerant capability over the reported fault-tolerant routing schemes in average flit deflection rate, average packet latency, saturation throughput and reliability by up to 13.5%, 9.8%, 10.6% and 17.5%, respectively. The layout area and power consumption are increased merely 3.5% and 2.6%.
Adoptive Transfer of Tumor-Specific Th2 Cells Eradicates Tumors by Triggering anIn SituInflammatory Immune Response
Authors: Lorvik Kristina Berg , Hammarström Clara , Fauskanger Marte , Haabeth Ole Audun Werner , Zangani Michael , Haraldsen Guttorm , Bogen Bjarne , Corthay Alexandre 
Published: September 2016

AbstractAdoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells; however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with IFNγ-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with MHC class II-negative myeloma. Th2 ACT efficiently eradicated subcutaneous myeloma in an antigen-specific fashion. Transferred Th2 cells persisted in vivo and conferred long-lasting immunity. Cancer eradication mediated by tumor-specific Th2 cells did not require B cells, natural killer T cells, CD8+ T cells, or IFNγ. Th2 ACT was also curative against B-cell lymphoma. Upon transfer, Th2 cells induced a type II inflammation at the tumor site with massive infiltration of M2-type macrophages producing arginase. In vivo blockade of arginase strongly inhibited Th2 ACT, consistent with a key role of arginase and M2 macrophages in myeloma elimination by Th2 cells. These results illustrate that cancer eradication may be achieved by induction of a tumor-specific Th2 inflammatory immune response at the tumor site. Thus, ACT with tumor-specific Th2 cells may represent a highly efficient immunotherapy protocol against cancer. Cancer Res; 76(23); 6864–76. ©2016 AACR.
Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI–Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation
Authors: Yamaoka Toshimitsu , Ohmori Tohru , Ohba Motoi , Arata Satoru , Kishino Yasunari , Murata Yasunori , Kusumoto Sojiro , Ishida Hiroo , Shirai Takao , Hirose Takashi , Ohnishi Tsukasa , Sasaki Yasutsuna 
Published: September 2016

Abstract
Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non–small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition of EGFR and Met tyrosine kinase activities. PC-9 lung adenocarcinoma cells harboring 15-bp deletions (Del E746_A750) in EGFR exon 19 were treated with increasing concentrations of the Met-TKI PHA665752 and 1 μmol/L gefitinib for 1 year; three resistant clones were established via Met amplification. The three dual-resistance cell lines (PC-9DR2, PC-9DR4, and PC-9DR6, designated as DR2, DR4, and DR6, respectively) exhibited different mechanisms for evading both EGFR and Met inhibition. None of the clones harbored a secondary mutation of EGFR T790M or a Met mutation. Insulin-like growth factor (IGF)/IGF1 receptor activation in DR2 and DR4 cells acted as a bypass signaling pathway. Met expression was attenuated to a greater extent in DR2 than in PC-9 cells, but was maintained in DR4 cells by overexpression of IGF-binding protein 3. In DR6 cells, Met was further amplified by association with HSP90, which protected Met from degradation and induced SET and MYND domain-containing 3 (SMYD3)-mediated Met transcription. This is the first report describing the acquisition of dual resistance mechanisms in NSCLC harboring an activating EGFR mutation to Met-TKI and EGFR-TKI following previous EGFR-TKI treatment. These results might inform the development of more effective therapeutic strategies for NSCLC treatment. Mol Cancer Ther; 15(12); 3040–54. ©2016 AACR.
Classification and Surgical Repair of Injuries Sustained During Transvenous Lead Extraction
Authors: Bashir Jamil , Fedoruk Lynn M. , Ofiesh John , Karim Shahzad S. , Tyers G. Frank O. 
Published: September 2016

Background—
Injuries to cardiac and venous structures during pacemaker and defibrillator lead extraction are serious complications that have been studied poorly. The incidence of these injuries is unknown but likely underestimated. No systematic multicenter review of these injuries or their management has been undertaken.

Methods and Results—
We interrogated our mandatory administrative database for all excimer laser extractions that sustained a cardiac or venous injury in the province of British Columbia. Injuries were classified according to presentation and compared with respect to nature of injury, type of repair, utilization of cardiopulmonary bypass, and outcome. Of 1082 excimer laser extractions over 19 years, 33 sustained an injury (3.0%). The majority of injuries occurred in women (21/33; 63.6%), and median age of oldest lead extracted was 10.8 (7.5, 12.2) years. A type 1 presentation, defined as circulatory collapse, was found in 12/33 patients (36.4%). A type 2 presentation, defined as progressive hypotension responsive to treatment, was found in 20/33 patients (60.6%). Over half the patients had a moderate or large injury, and cardiopulmonary bypass was required in 13 patients with extensive injury. Despite the presence of devastating injuries, the immediate availability of aggressive salvage measures resulted in a survival of 87.9% of patients at 30 days.

Conclusions—
The immediate availability of a cardiovascular surgeon, perfusionist, and cardiopulmonary bypass pump facilitates lifesaving repair of injuries sustained during laser lead extraction. The size and complexity of injury correlates closely with the presentation, blood loss, and need for cardiopulmonary bypass to facilitate repair.
Prevalence and Electrocardiographic and Electrophysiological Characteristics of Idiopathic Ventricular Arrhythmias Originating From Intramural Foci in the Left Ventricular Outflow Tract
Authors: Yamada Takumi , Doppalapudi Harish , Maddox William R. , McElderry H. Thomas , Plumb Vance J. , Kay G. Neal 
Published: September 2016

Backgrounds—
Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from both the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the prevalence and electrocardiographic and electrophysiological characteristics of these idiopathic intramural LVOT VAs when compared with the idiopathic endocardial and epicardial LVOT VAs.

Methods and Results—
We studied 82 consecutive VAs with origins in the aortomitral continuity (n=30), LV summit (n=34), and intramural site (n=18). The maximum deflection index (the time to the maximum deflection in the precordial leads/QRS duration) was the largest in LV summit VAs (0.52±0.07), smallest in aortomitral continuity VAs (0.45±0.06), and midrange in intramural VAs (0.49±0.05). The electrocardiographic and electrophysiological characteristics of the intramural LVOT VAs were similar to those of the aortomitral continuity VAs. The intramural LVOT VAs exhibited a significantly smaller R-wave amplitude ratio in leads III to II, and ratio of the Q-wave amplitude in leads aVL to aVR, and a significantly earlier and later local ventricular activation time relative to the QRS onset at the His bundle and successful ablation sites than the LV summit VAs, respectively.

Conclusions—
Intramural sites account for a significant proportion of LVOT VAs. The electrocardiographic and electrophysiological characteristics of the idiopathic intramural LVOT VAs were midrange between those of the idiopathic endocardial and epicardial LVOT VAs, and more similar to those of the idiopathic endocardial LVOT VAs than those of the idiopathic epicardial LVOT VAs.
Left Atrial and Left Atrial Appendage 4D Blood Flow Dynamics in Atrial Fibrillation
Authors: Markl Michael , Lee Daniel C. , Furiasse Nicholas , Carr Maria , Foucar Charles , Ng Jason , Carr James , Goldberger Jeffrey J. 
Published: September 2016

Background—
Atrial 4D flow magnetic resonance imaging was used for the characterization of left atrial (LA) and left atrial appendage (LAA) flow dynamics in patients with atrial fibrillation (AF).

Methods and Results—

4D flow magnetic resonance imaging measured in vivo 3D blood flow velocities in 60 AF patients and 15 controls. Anatomic maps of LA and LAA stasis and velocity were calculated to quantify atrial peak velocity, mean velocity, and stasis (velocities <0.1 m/s). In a substudy with 30 AF patients, 4D flow metrics were compared with Doppler transesophageal echocardiography. For all 15 controls, LAA mean and peak velocities were consistently lower (by 21%/12%;
P
<0.001) while LAA stasis was higher (by 58%;
P
<0.001) compared with the LA. In contrast, lower LAA velocity and increased LAA stasis were only found in a fraction (38 of 60) of AF patients. In AF patients, increased CHA
2
DS
2
-VASc score was associated with significantly (
P
<0.043) reduced LA velocities and elevated stasis. There was a heterogeneous expression of atrial flow dynamics, and 25% to 68% of AF patients demonstrated flow in the normal range: 25%/68% for LA/LAA stasis and 38%/60% for LA/LAA peak velocities. Transesophageal echocardiography velocities modestly but significantly (
P
<0.05) correlated with 4D flow–based LA velocities (
r
=0.41) and stasis (
r
=−0.39).

Conclusions—

AF resulted in overall impaired but individually variable flow dynamics in both the LA and LAA. AF patients demonstrated atrial flow in the normal range, despite elevated CHA
2
DS
2
-VASc score.
Evidence for Gap Flows in the Birch Creek Valley, Idaho
Authors: Finn D. , Reese B. , Butler B. , Wagenbrenner N. , Clawson K. L. , Rich J. , Russell E. , Gao Z. , Liu H. 
Published: September 2016

Abstract
A field study was conducted of flows in the Birch Creek Valley in eastern Idaho. There is a distinct topographic constriction in the Birch Creek Valley that creates two subbasins: an upper and lower valley. The data were classified into one of three groups based on synoptic influence (weak/absent, high wind speeds, and other evidence of synoptic influence). Gap flows commonly developed downwind of the constriction in association with the weak/absent group but also occurred in association with the two synoptic groups suggesting the potential for more diverse origins. In general, the frequency and strength of gap flows appeared to be linked to the development of the requisite thermal regime and minimization of any synoptically driven southerly winds that would suppress outflows. Gap flows were characterized by high wind speeds with jetlike vertical profiles along the axis of the lower valley. For all three groups the morning transition in the upper valley and western sidewall usually proceeded slightly ahead of the lower valley, consistent with the principles of the topographic amplification factor. The persistence of southerly winds in the lower valley past evening transition inhibited the development of gap flows, promoted strong nighttime inversions, and delayed the onset of morning transition relative to the upper valley. Nocturnal temperature inversions in the lower valley were largely eliminated with the onset of strong gap flows resulting in earlier morning transitions there. The form for a method of predicting gap flow wind speeds is proposed.