bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shank2 mutant mice display a hypersecretory response to cholera toxin
Authors: Jung Eun Suk , Park Joonhee , Gee Heon Yung , Jung Jinsei , Noh Shin Hye , Lee Jung‐Soo , Richter Wito , Namkung Wan , Lee Min Goo 
Published: January 2014

Key points
Among the three Shank proteins in human (Shank1–3), Shank2 is abundantly expressed in epithelial cells. However, the in vivo physiological role of Shank2 in epithelial transport remains elusive.
The functional activity and expression of cystic fibrosis transmembrane conductance regulator (CFTR) and fluid secretion in the gastrointestinal epithelia were examined in the intestines of Shank2+/+ and Shank2−/− mice using an integrated molecular and physiological approach.
Shank2 deletion augmented the CFTR‐mediated short‐circuit current in the mouse colon and profoundly increased the cholera toxin‐induced fluid accumulation in the mouse intestine.
Shank2 appears to be a key molecule regulating epithelial fluid secretion. Modulation of Shank2‐mediated function would be helpful to treat diseases associated with hypersecretion or hyposecretion in epithelia.
AbstractShank2 is a PDZ (PSD‐95/discs large/ZO‐1)‐based adaptor that has been suggested to regulate membrane transporting proteins in the brain and epithelial tissues. Here, we report that Shank2 mutant (Shank2−/−) mice exhibit aberrant fluid and ion transport in the intestine. Molecular characterization using epithelial tissues from Shank2+/+ and Shank2−/− mice revealed that a long spliceoform of Shank2 (Shank2E) is predominantly expressed in the pancreatic, renal and intestinal epithelia. In functional assays, deletion of Shank2 increased the cystic fibrosis transmembrane conductance regulator (CFTR)‐dependent short‐circuit currents by 84% (P < 0.05) and 101% (P < 0.05) in the mouse colon and rectum, respectively. Disruption of the CFTR–Shank2–phosphodiesterase 4D protein complex appeared to be mostly responsible for the changes in CFTR activities. Notably, Shank2 deletion profoundly increased cholera toxin‐induced fluid accumulation in the mouse intestine (∼90%, P < 0.01). Analyses with chemical inhibitors confirmed that the hyperactivation of CFTR channel function is responsible for the increased response to cholera toxin. These results suggest that Shank2 is a key molecule that participates in epithelial homeostasis, in particular to prevent overt secretory responses caused by epithelial pathogens.
A Comparison of Women With Fibromyalgia Syndrome to Criterion Fitness Standards: A Pilot Study
Authors: Jones C. Jessie , Rakovski Carter , Rutledge Dana , Gutierrez Angela 
Published: January 2014

Purpose:To compare fitness of women with fibromyalgia syndrome (FMS) aged 50+ with performance standards associated with functional independence in late life.Methods:Data came from a longitudinal study tracking physical and cognitive function of 93 women with FMS and included the most recent symptoms, activity levels, and fitness assessments.Results:Most women performed below criterion-referenced fitness standards for all measures. Nearly 90% percent of those < 70 years scored below the standard for lower body strength. Only ~20% of respondents < 70 years old met the criteria for aerobic endurance. A third of those aged over 70 met the standard in agility and dynamic balance. Physical activity was positively associated with fitness performance, while pain and depression symptoms were negatively associated.Discussion:High proportions of women with FMS do not meet fitness standards recommended for maintaining physical independence in late life, indicating a risk for disability. Regular fitness assessments and targeted exercise interventions are warranted.
Effect of Foam Rolling and Static Stretching on Passive Hip-Flexion Range of Motion
Authors: Mohr Andrew R. , Long Blaine C. , Goad Carla L. 
Published: January 2014

Context:Many athletes report that foam rollers help release tension in their muscles, thus resulting in greater range of motion (ROM) when used before stretching. To date, no investigators have examined foam rollers and static stretching.Objective:To determine if foam rolling before static stretching produces a significant change in passive hip-flexion ROM.Design:Controlled laboratory study.Setting:Research laboratory.Participants:40 subjects with less than 90° of passive hip-flexion ROM and no lower-extremity injury in the 6 mo before data collection.Interventions:During each of 6 sessions, subjects' passive hip-flexion ROM was measured before and immediately after static stretching, foam rolling and static stretching, foam rolling, or nothing (control). To minimize accessory movement of the hip and contralateral leg, subjects lay supine with a strap placed across their hip and another strap located over the uninvolved leg just superior to the patella. A bubble inclinometer was then aligned on the thigh of the involved leg, with which subjects then performed hip flexion.Main Outcome Measure:Change in passive hip-flexion ROM from the preintervention measure on day 1 to the postintervention measure on day 6.Results:There was a significant change in passive hip-flexion ROM regardless of treatment (F3,17 = 8.06, P = .001). Subjects receiving foam roll and static stretch had a greater change in passive hip-flexion ROM compared with the static-stretch (P = .04), foam-rolling (P = .006), and control (P = .001) groups.Conclusions:Our results support the use of a foam roller in combination with a static-stretching protocol. If time allows and maximal gains in hip-flexion ROM are desired, foam rolling the hamstrings muscle group before static stretching would be appropriate in noninjured subjects who have less than 90° of hamstring ROM.
The Accuracy of the Functional Movement Screen to Identify Individuals With an Elevated Risk of Musculoskeletal Injury
Authors: Krumrei Kirk , Flanagan Molly , Bruner Josh , Durall Chris 
Published: January 2014

Clinical Scenario:Injuries are somewhat commonplace in highly active populations. One strategy for reducing injuries is to identify individuals with an elevated injury risk before participation so that remediative interventions can be provided. Preparticipation screenings have traditionally entailed strength and flexibility measures thought to be indicative of inflated injury risk. Some researchers, however, have suggested that functional movements/tasks should be assessed to help identify individuals with a high risk of future injury. One assessment tool used for this purpose is the Functional Movement Screen (FMS). The FMS generates a numeric score based on performance attributes during 7 dynamic tasks; this score is purported to reflect future injury risk. Expanding interest in the FMS has led researchers to investigate how accurately it can identify individuals with an increased risk of injury.Focused Clinical Question:Can the Functional Movement Screen accurately identify highly active individuals with an elevated risk of injury?
Triggering effective social support for online groups
Authors: Kumar Rohit , Rosé Carolyn P. 
Published: January 2014

Conversational agent technology is an emerging paradigm for creating a social environment in online groups that is conducive to effective teamwork. Prior work has demonstrated advantages in terms of learning gains and satisfaction scores when groups learning together online have been supported by conversational agents that employ Balesian social strategies. This prior work raises two important questions that are addressed in this article. The first question is one of generality. Specifically, are the positive effects of the designed support specific to learning contexts? Or are they in evidence in other collaborative task domains as well? We present a study conducted within a collaborative decision-making task where we see that the positive effects of the Balesian social strategies extend to this new context. The second question is whether it is possible to increase the effectiveness of the Balesian social strategies by increasing the context sensitivity with which the social strategies are triggered. To this end, we present technical work that increases the sensitivity of the triggering. Next, we present a user study that demonstrates an improvement in performance of the support agent with the new, more sensitive triggering policy over the baseline approach from prior work.
The technical contribution of this article is that we extend prior work where such support agents were modeled using a composition of conversational behaviors integrated within an event-driven framework. Within the present approach, conversation is orchestrated through context-sensitive triggering of the composed behaviors. The core effort involved in applying this approach involves building a set of triggering policies that achieve this orchestration in a time-sensitive and coherent manner. In line with recent developments in data-driven approaches for building dialog systems, we present a novel technique for learning behavior-specific triggering policies, deploying it as part of our efforts to improve a socially capable conversational tutor agent that supports collaborative learning.
Gene Silencing Associated with SWI/SNF Complex Loss during NSCLC Development
Authors: Song Shujie , Walter Vonn , Karaca Mehmet , Li Ying , Bartlett Christopher S. , Smiraglia Dominic J. , Serber Daniel , Sproul Christopher D. , Plass Christoph , Zhang Jiren , Hayes D. Neil , Zheng Yanfang , Weissman Bernard E. 
Published: January 2014

Abstract
The SWI/SNF chromatin-remodeling complex regulates gene expression and alters chromatin structures in an ATP-dependent manner. Recent sequencing efforts have shown mutations in BRG1 (SMARCA4), one of two mutually exclusive ATPase subunits in the complex, in a significant number of human lung tumor cell lines and primary non–small cell lung carcinoma (NSCLC) clinical specimens. To determine how BRG1 loss fuels tumor progression in NSCLC, molecular profiling was performed after restoration of BRG1 expression or treatment with a histone deacetylase inhibitor or a DNA methyltransferase (DNMT) inhibitor in a BRG1-deficient NSCLC cells. Importantly, validation studies from multiple cell lines revealed that BRG1 reexpression led to substantial changes in the expression of CDH1, CDH3, EHF, and RRAD that commonly undergo silencing by other epigenetic mechanisms during NSCLC development. Furthermore, treatment with DNMT inhibitors did not restore expression of these transcripts, indicating that this common mechanism of gene silencing did not account for their loss of expression. Collectively, BRG1 loss is an important mechanism for the epigenetic silencing of target genes during NSCLC development.
Implications: Inactivation of the SWI/SNF complex provides a novel mechanism to induce gene silencing during NSCLC development. Mol Cancer Res; 12(4); 560–70. ©2014 AACR.
RapidCaP, a Novel GEM Model for Metastatic Prostate Cancer Analysis and Therapy, Reveals Myc as a Driver of Pten-Mutant Metastasis
Authors: Cho Hyejin , Herzka Tali , Zheng Wu , Qi Jun , Wilkinson John E. , Bradner James E. , Robinson Brian D. , Castillo-Martin Mireia , Cordon-Cardo Carlos , Trotman Lloyd C. 
Published: January 2014

Abstract
Genetically engineered mouse (GEM) models are a pillar of functional cancer research. Here, we developed RapidCaP, a GEM modeling system that uses surgical injection for viral gene delivery to the prostate. We show that in Pten deficiency, loss of p53 suffices to trigger metastasis to distant sites at greater than 50% penetrance by four months, consistent with results from human prostate cancer genome analysis. Live bioluminescence tracking showed that endogenous primary and metastatic disease responds to castration before developing lethal castration resistance. To our surprise, the resulting lesions showed no activation of Akt but activation of the Myc oncogene. Using RapidCaP, we find that Myc drives local prostate metastasis and is critical for maintenance of metastasis, as shown by using the Brd4 inhibitor JQ1. Taken together, our data suggest that a “MYC-switch” away from AKT forms a critical and druggable event in PTEN-mutant prostate cancer metastasis and castration resistance.
Significance: The RapidCaP system introduces fast and flexible genetics for functional analysis and therapy for endogenous metastatic prostate cancer. The approach introduces targeting of MYC as a critical strategy against PTEN-deficient lethal prostate cancer. Cancer Discov; 4(3); 318–33. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 259
Inhibition of KRAS-Driven Tumorigenicity by Interruption of an Autocrine Cytokine Circuit
Authors: Zhu Zehua , Aref Amir R. , Cohoon Travis J. , Barbie Thanh U. , Imamura Yu , Yang Shenghong , Moody Susan E. , Shen Rhine R. , Schinzel Anna C. , Thai Tran C. , Reibel Jacob B. , Tamayo Pablo , Godfrey Jason T. , Qian Zhi Rong , Page Asher N. , Maciag Karolina , Chan Edmond M. , Silkworth Whitney , Labowsky Mary T. , Rozhansky Lior , Mesirov Jill P. , Gillanders William E. , Ogino Shuji , Hacohen Nir , Gaudet Suzanne , Eck Michael J. , Engelman Jeffrey A. , Corcoran Ryan B. , Wong Kwok-Kin , Hahn William C. , Barbie David A. 
Published: January 2014

Abstract
Although the roles of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well established, KRAS activates additional pathways required for tumor maintenance, the inhibition of which are likely to be necessary for effective KRAS-directed therapy. Here, we show that the IκB kinase (IKK)–related kinases Tank-binding kinase-1 (TBK1) and IKKϵ promote KRAS-driven tumorigenesis by regulating autocrine CCL5 and interleukin (IL)-6 and identify CYT387 as a potent JAK/TBK1/IKKϵ inhibitor. CYT387 treatment ablates RAS-associated cytokine signaling and impairs Kras-driven murine lung cancer growth. Combined CYT387 treatment and MAPK pathway inhibition induces regression of aggressive murine lung adenocarcinomas driven by Kras mutation and p53 loss. These observations reveal that TBK1/IKKϵ promote tumor survival by activating CCL5 and IL-6 and identify concurrent inhibition of TBK1/IKKϵ, Janus-activated kinase (JAK), and MEK signaling as an effective approach to inhibit the actions of oncogenic KRAS.
Significance: In addition to activating MAPK and PI3K, oncogenic KRAS engages cytokine signaling to promote tumorigenesis. CYT387, originally described as a selective JAK inhibitor, is also a potent TBK/IKKϵ inhibitor that uniquely disrupts a cytokine circuit involving CCL5, IL-6, and STAT3. The efficacy of CYT387-based treatment in murine Kras-driven lung cancer models uncovers a novel therapeutic approach for these refractory tumors with immediate translational implications. Cancer Discov; 4(4); 452–65. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 377
Effect of Radiofrequency Catheter Ablation for Atrial Fibrillation on Morbidity and Mortality
Authors: Chang Chia-Hsuin , Lin Jou-Wei , Chiu Fu-Chun , Caffrey James L. , Wu Li-Chiu , Lai Mei-Shu 
Published: January 2014

Background—
This study examined the effect of radiofrequency catheter ablation (RFA) on reducing morbidity and mortality among patients with atrial fibrillation (AF).

Methods and Results—

A retrospective cohort of patients with AF without prior stroke or heart failure (HF) who underwent RFA between 2003 and 2009 was identified using Taiwan’s National Health Insurance claims database. Outpatients with AF who met the same enrollment criteria but did not receive RFA were matched (≤1:20) by hospitals and dates to serve as controls. Outcomes of interest were death, stroke, or hospitalization for HF. A proportional hazard Cox regression model adjusted by propensity scores (based on age, sex, hypertension, diabetes mellitus, comorbidities, medications, and medical resource utilization) was applied to estimate the hazard ratio and 95% confidence interval. A total of 846 patients with AF who received RFA and 11 324 matched AF controls were included, with a mean follow-up of 3.74 and 3.96 years, respectively. RFA was associated with a lower hazard for stroke (hazard ratio, 0.57; 95% confidence interval, 0.35–0.94;
P
=0.026). The reduction in the hazard for death and HF did not reach statistical significance (hazard ratio, 0.88; 95% confidence interval, 0.62–1.23;
P
=0.451 and hazard ratio, 0.78; 95% confidence interval, 0.55–1.12;
P
=0.185, respectively). Additional analysis using death as a competing risk showed similar results for stroke and HF.

Conclusions—
RFA did not reduce mortality or hospitalization for HF during the immediate 3.5-year follow-up. Although a beneficial effect on stroke prevention associated with RFA was suggested, residual confounding attributable to unmeasured factors remains a concern.
Time Course of Inflammation, Myocardial Injury, and Prothrombotic Response After Radiofrequency Catheter Ablation for Atrial Fibrillation
Authors: Lim Han S. , Schultz Carlee , Dang Jerry , Alasady Muayad , Lau Dennis H. , Brooks Anthony G. , Wong Christopher X. , Roberts-Thomson Kurt C. , Young Glenn D. , Worthley Matthew I. , Sanders Prashanthan , Willoughby Scott R. 
Published: January 2014

Background—
Inflammation has been linked to the genesis of stroke in atrial fibrillation (AF) and is implicated in early recurrent arrhythmia after AF ablation. We aimed to define the time course of inflammation, myocardial injury, and prothrombotic markers after radiofrequency ablation for AF and its relation to AF recurrence.

Methods and Results—

Ninety consecutive AF patients (53% paroxysmal) undergoing radiofrequency ablation were recruited. High-sensitivity C-reactive protein (hs-CRP), Troponin-T, creatine kinase-MB, fibrinogen, and D-Dimer concentrations were measured at baseline, at 1, 2, 3, 7 days, and at 1 month after ablation. AF recurrence was documented at 3 days and at 1, 3, and 6 months follow-up. Troponin-T and creatine kinase-MB peaked at day 1 after procedure (both
P
<0.05). Hs-CRP peaked at day 3 after procedure (
P
<0.05). Fibrinogen (
P
<0.05) and D-Dimer (
P
<0.05) concentrations were significantly elevated at 1 week after procedure. Ln hs-CRP elevation correlated with Ln Troponin-T and fibrinogen elevation. The extent of Ln hs-CRP, Ln Troponin-T, and fibrinogen elevation predicted early AF recurrence within 3 days after procedure (
P
<0.05, respectively), but not at 3 and 6 months.

Conclusions—
Patients undergoing radiofrequency ablation for AF exhibit an inflammatory response within 3 days. The extent of inflammatory response predicts early AF recurrence but not late recurrence. Prothrombotic markers are elevated at 1 week after ablation and may contribute to increased risk of early thrombotic events after AF ablation.
Is there a need for MRI within 24 hours after CT-guided percutaneous thermoablation of the liver?
Authors: Ringe Kristina Imeen , Wacker Frank , Raatschen Hans-Jürgen 
Published: January 2014

Background Radiofrequency (RFA) and microwave ablation (MWA) are established minimally invasive techniques for treatment of hepatic tumors. Purpose To compare technical success and accuracy of hepatic thermoablation using computed tomography (CT) and magnetic resonance imaging (MRI) acquired 24 h after ablation with regard to evaluation of the post-interventional ablation zone and local tumor recurrence (LTR), and to assess whether additional MRI within 24 h is beneficial. Material and Methods Thirty-two patients (23 men, 9 women; mean age, 60 years) with 48 lesions were included in this retrospective study. CT was performed immediately and MRI was performed 24 h after ablation. Diameter and volume calculations of the ablation zone were compared (T-Test). Technical success and ablation margin distinction, shape, and configuration were evaluated (κ-statistic). Local effectiveness was calculated based on follow-up imaging. Technical success and ablation margin features were correlated with LTR (log-rank test, Fisher's exact test). Results Ablation zone volumes were significantly higher with MRI compared to CT ( P < 0.05; mean volume, 55.19 and 45.97 mL). Agreement between CT and MRI for technical success was good (κ = 0.801) and for margin conspicuity fair (κ = 0.289). LTR was 26.1% (mean follow-up, 11.7 months). LTR showed no correlation with technical success or margin conspicuity. Conclusion CT and MRI are suited for early evaluation of technical success after thermoablation. Within 24 h a significant increase of the ablation volume is observed, which has to be taken into account when interpreting immediate postprocedural imaging and treating lesions near critical structures. Additional MRI 24 h after ablation seems of limited value regarding prognosis of LTR, especially with regards to evaluation of ablation margin shape and conspicuity.
Contrast-enhanced ultrasound using real-time contrast harmonic imaging in invasive breast cancer: comparison of enhancement dynamics with three different doses of contrast agent
Authors: Saracco Ariel , Szabó Botond K , Aspelin Peter , Leifland Karin , Tánczos Ervin , Wilczek Brigitte , Axelsson Rimma 
Published: January 2014

BackgroundIn the last few years new potential applications have been developed for contrast-enhanced ultrasound (CEUS) and the management of breast diseases, but there is still some debate concerning the optimal dose to evaluate breast lesions, especially as a diagnostic tool.PurposeTo compare different CEUS doses of injected contrast agent in order to establish an optimal dose for the diagnosis of invasive breast cancer.Material and MethodsIn Group A we compared the bolus dose of 1.2 mL vs. 2.4 mL and in Group B we compared the bolus dose of 2.4 mL vs. 4.8 mL (26 and 25 invasive carcinomas, respectively). CEUS was performed in real-time contrast harmonic imaging (CHI) using a L9-3 MHz probe. All examinations were recorded in a contrast side/side imaging mode loop for 120 s. Wash-in and wash-out patterns of the contrast agent were analyzed with advanced US quantification software and kinetic curves were used for statistical analysis.ResultsIn Group B (2.4 mL vs. 4.8 mL), more and stronger correlation was found among kinetic parameters (area under the curve, P < 0.00001; lognormal model parameters, μ, P = 0.0007 and σ, P < 0.0001; mean transit time, P < 0.0001; model-based wash-out ratios, W21m, P = 0.0002; W50m, P = 0.0001; time-to-peak, P = 0.005) as compared to Group A (1.2 mL vs. 2.4 mL).ConclusionThe optimal way to evaluate kinetic features of invasive breast tumors using real-time CEUS is with an injection of contrast agent of either 2.4 mL or 4.8 mL.