bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is hip strength a risk factor for patellofemoral pain? A systematic review and meta-analysis
Authors: Rathleff M S , Rathleff C R , Crossley K M , Barton C J 
Published: April 2014

ObjectiveTo evaluate and synthesise the literature on hip strength among patients with patellofemoral pain (PFP) to address the following: (1) differentiate between hip strength as a risk factor and associated deficit in PFP; (2) describe hip strength in men and women with PFP across different age ranges; (3) investigate the effects of hip strengthening on biomechanical knee variables associated with PFP development.MethodsMEDLINE, CINAHL, Web of Science, SportDiscus and Google Scholar were searched in November 2013 for studies investigating hip strength among patients with PFP. Two reviewers independently assessed papers for inclusion and quality. Means and SDs were extracted from each included study to allow effect size calculations and comparisons of results.ResultsModerate-to-strong evidence from prospective studies indicates no association between isometric hip strength and risk of developing PFP. Moderate evidence from cross-sectional studies indicates that men and women with PFP have lower isometric hip musculature strength compared to pain-free individuals. Limited evidence indicates that adolescents with PFP do not have the same strength deficits as adults with PFP.ConclusionsThis review highlights a possible discrepancy between prospective and cross-sectional research. Cross-sectional studies indicate that adult men and women with PFP appear to have lower hip strength compared to pain-free individuals. Contrary to this, a limited number of prospective studies indicate that there may be no association between isometric hip strength and risk of developing PFP. Therefore, reduced hip strength may be a result of PFP rather than the cause.
Barriers to life jacket use among adult recreational boaters
Authors: Quistberg D Alex , Quan Linda , Ebel Beth E , Bennett Elizabeth E , Mueller Beth A 
Published: April 2014

ObjectiveTo identify barriers to life jacket use.DesignCross-sectional survey.SettingNine public boat ramps in western Washington State, USA, August–November, 2008.Participants675 adult boaters (>18 years) on motor boats <26 feet long.Main outcomeLow or no life jacket use (0–50% of time) versus high life jacket use (51–100% of time).ResultsLow/no life jacket use (0–50% of time) was associated with longer boat length (per foot, risk ratio [RR] 1.03, 95% CI 1.02 to 1.05), alcohol use (RR 1.11, 95% CI 1.01 to 1.20), perception of life jackets as ‘uncomfortable’ (RR 1.29, 95% CI 1.09 to 1.52), perceived greater level of swimming ability (RR 1.25, 95% CI 1.03 to 1.53 for ‘expert swimmer’) and possibly with lack of confidence that a life jacket may save one from drowning (RR 1.13, 95% CI 0.96 to 1.32). Low life jacket use was less likely when an inflatable life jacket was the primary life jacket used by a subject (RR 0.77, 95% CI 0.63 to 0.94), a child was onboard (RR 0.88, 95% CI 0.79 to 0.99) or if the respondent had taken a boating safety class (RR 0.94, 95% CI 0.87 to 1.01).ConclusionsLife jacket use may increase with more comfortable devices, such as inflatable life jackets, and with increased awareness of their efficacy in preventing drowning. Boater education classes may be associated with increased life jacket use among adults.
A case–control study of boat-related injuries and fatalities in Washington State
Authors: Stempski Sarah , Schiff Melissa , Bennett Elizabeth , Quan Linda 
Published: April 2014

ObjectivesTo identify risk factors associated with boat-related injuries and deaths.MethodsWe performed a case–control study using the Washington Boat Accident Investigation Report Database for 2003–2010. Cases were fatally injured boat occupants, and controls were non-fatally injured boat occupants involved in a boating incident. We evaluated the association between victim, boat and incident factors and risk of death using Poisson regression to estimate RRs and 95% CIs.ResultsOf 968 injured boaters, 26% died. Fatalities were 2.6 times more likely to not be wearing a personal flotation device (PFD) and 2.2 times more likely to not have any safety features on their boat compared with those who survived. Boating fatalities were more likely to be in a non-motorised boat, to have alcohol involved in the incident, to be in an incident that involved capsizing, sinking, flooding or swamping, and to involve a person leaving the boat voluntarily, being ejected or falling than those who survived.ConclusionsIncreasing PFD use, safety features on the boat and alcohol non-use are key strategies and non-motorised boaters are key target populations to prevent boating deaths.
Outcomes of surgery for chronic exertional compartment syndrome in a military population
Authors: Roberts Andrew J , Krishnasamy P , Quayle J M , Houghton J M 
Published: April 2014

AimTo determine the outcome following fasciectomy for chronic exertional compartment syndrome (CECS) in the UK military, and the association between presurgical intramuscular pressure (IMP) and outcome.MethodsAll patients who underwent fasciectomy for anterior CECS were identified between 2007 and 2010. Presurgery and postsurgery military medical grading for leg function was extracted from the medical records system. The Wilcoxon signed-rank test compared grades before and after surgery. Spearman's rank correlation examined the relationship between IMP and outcome.ResultsPresurgery and postsurgery grading was available for 63% of patients. These patients had significantly better leg function after surgery (Z=−3.63, p<0.001). Of these, 49% improved by at least one grade, 36% showed no improvement in grading and 15% had a poorer outcome. There were no significant correlations between IMP and outcome.ConclusionsA large proportion of patients do not return to full fitness following fasciectomy in the military population. This is in line with a recent study in the US military, but conflicts with most civilian reports. The reasons for these differences are not clear. Furthermore, the lack of a relationship between IMP and outcome questions the role of pressure in this condition. These results suggest that the role of postoperative rehabilitation protocols and other conservative options should be explored.
Adrenal incidentalomas: management in British district general hospitals
Authors: Davenport Emily , Lang Ping Nam Pitsien , Wilson Michael , Reid Alastair , Aspinall Sebastian 
Published: April 2014

Abstract

Introduction
Adrenal incidentalomas have become a common clinical dilemma with the increasing use and resolution of cross sectional imaging modalities.

Objectives
This retrospective observational study examined the management of adrenal incidentalomas in district general hospitals in Northumbria and adherence to current guidelines.

Materials and methods
We searched 4028 abdominal CT scans performed in Northumbria between 1 January and 31 December 2010. All patients with an incidental adrenal lesion were identified and their clinical records reviewed.

Results
75 patients with adrenal incidentalomas were identified. Of these, only 13 (17%) were referred for specialist review with a further two patients undergoing additional evaluation by the primary medical team; 80% received no biochemical investigation or follow-up. Comorbidity may have affected the decision in a proportion, but 36 of 62 patients (58%) had no comorbidities precluding additional evaluation. In contrast, all patients reviewed by an endocrine specialist were appropriately investigated and managed, the majority conservatively, with three requiring adrenalectomy for phaeochromocytoma or cortisol secreting adenomas. In the patients with an incidentaloma, comorbidities which may be attributable to autonomous adrenal cortisol or aldosterone release were higher than regional averages, suggesting possible undiagnosed functional tumours.

Conclusions
The management of adrenal incidentalomas in British district general hospitals in Northumbria shows poor adherence to guidelines. Adherence was significantly better in those patients managed by an endocrine specialist. We suggest a pathway for the management and referral process.
Analysis of Search and Browsing Behavior of Young Users on the Web
Authors: Duarte Torres Sergio , Weber Ingmar , Hiemstra Djoerd 
Published: April 2014

The Internet is increasingly used by young children for all kinds of purposes. Nonetheless, there are not many resources especially designed for children on the Internet and most of the content online is designed for grown-up users. This situation is problematic if we consider the large differences between young users and adults since their topic interests, computer skills, and language capabilities evolve rapidly during childhood. There is little research aimed at exploring and measuring the difficulties that children encounter on the Internet when searching for information and browsing for content. In the first part of this work, we employed query logs from a commercial search engine to quantify the difficulties children of different ages encounter on the Internet and to characterize the topics that they search for. We employed query metrics (e.g., the fraction of queries posed in natural language), session metrics (e.g., the fraction of abandoned sessions), and click activity (e.g., the fraction of ad clicks). The search logs were also used to retrace stages of child development. Concretely, we looked for changes in interests (e.g., the distribution of topics searched) and language development (e.g., the readability of the content accessed and the vocabulary size).
In the second part of this work, we employed toolbar logs from a commercial search engine to characterize the browsing behavior of young users, particularly to understand the activities on the Internet that trigger search. We quantified the proportion of browsing and search activity in the toolbar sessions and we estimated the likelihood of a user to carry out search on the Web vertical and multimedia verticals (i.e., videos and images) given that the previous event is another search event or a browsing event.
We observed that these metrics clearly demonstrate an increased level of confusion and unsuccessful search sessions among children. We also found a clear relation between the reading level of the clicked pages and characteristics of the users such as age and educational attainment.
In terms of browsing behavior, children were found to start their activities on the Internet with a search engine (instead of directly browsing content) more often than adults. We also observed a significantly larger amount of browsing activity for the case of teenager users. Interestingly we also found that if children visit knowledge-related Web sites (i.e., information-dense pages such as Wikipedia articles), they subsequently do more Web searches than adults. Additionally, children and especially teenagers were found to have a greater tendency to engage in multimedia search, which calls to improve the aggregation of multimedia results into the current search result pages.
Src Kinase Is a Novel Therapeutic Target in Lymphangioleiomyomatosis
Authors: Tyryshkin Alexey , Bhattacharya Abhisek , Eissa N. Tony 
Published: April 2014

Abstract
Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease affecting some women with tuberous sclerosis complex (TSC). Sporadic LAM can develop in women without TSC, owing to somatic mutations in the TSC2 gene. Accumulating evidence supports the view of LAM as a low-grade, destructive, metastasizing neoplasm. The mechanisms underlying the metastatic capability of LAM cells remain poorly understood. The observed behavior of LAM cells with respect to their infiltrative growth pattern, metastatic potential, and altered cell differentiation bears similarity to cells undergoing epithelial–mesenchymal transition. Here, we report increased levels of active Src kinase in LAM lungs and in TSC2−/− cells, caused by a reduction of autophagy. Furthermore, increased Src kinase activation promoted migration, invasion, and inhibition of E-cadherin expression in TSC2−/− cells by upregulating the transcription factor Snail. Notably, Src kinase inhibitors reduced migration and invasion properties of TSC2−/− cells and attenuated lung colonization of intravenously injected TSC2−/− cells in vivo to a greater extent than control TSC2+/+ cells. Our results reveal mechanistic basis for the pathogenicity of LAM cells and they rationalize Src kinase as a novel therapeutic target for treatment of LAM and TSC. Cancer Res; 74(7); 1996–2005. ©2014 AACR.
VISTA Is an Immune Checkpoint Molecule for Human T Cells
Authors: Lines J. Louise , Pantazi Eirini , Mak Justin , Sempere Lorenzo F. , Wang Li , O'Connell Samuel , Ceeraz Sabrina , Suriawinata Arief A. , Yan Shaofeng , Ernstoff Marc S. , Noelle Randolph 
Published: April 2014

AbstractV-domain Ig suppressor of T cell activation (VISTA) is a potent negative regulator of T-cell function that is expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses in mice. In humans, blockade of the related programmed cell death 1 (PD-1) pathway has shown great potential in clinical immunotherapy trials. Here, we report the structure of human VISTA and examine its function in lymphocyte negative regulation in cancer. VISTA is expressed predominantly within the hematopoietic compartment with highest expression within the myeloid lineage. VISTA-Ig suppressed proliferation of T cells but not B cells and blunted the production of T-cell cytokines and activation markers. Our results establish VISTA as a negative checkpoint regulator that suppresses T-cell activation, induces Foxp3 expression, and is highly expressed within the tumor microenvironment. By analogy to PD-1 and PD-L1 blockade, VISTA blockade may offer an immunotherapeutic strategy for human cancer. Cancer Res; 74(7); 1924–32. ©2013 AACR.
VISTA Regulates the Development of Protective Antitumor Immunity
Authors: Le Mercier Isabelle , Chen Wenna , Lines Janet L. , Day Maria , Li Jiannan , Sergent Petra , Noelle Randolph J. , Wang Li 
Published: April 2014

AbstractV-domain Ig suppressor of T-cell activation (VISTA) is a novel negative checkpoint ligand that is homologous to PD-L1 and suppresses T-cell activation. This study demonstrates the multiple mechanisms whereby VISTA relieves negative regulation by hematopoietic cells and enhances protective antitumor immunity. VISTA is highly expressed on myeloid cells and Foxp3+CD4+ regulatory cells, but not on tumor cells within the tumor microenvironment (TME). VISTA monoclonal antibody (mAb) treatment increased the number of tumor-specific T cells in the periphery and enhanced the infiltration, proliferation, and effector function of tumor-reactive T cells within the TME. VISTA blockade altered the suppressive feature of the TME by decreasing the presence of monocytic myeloid-derived suppressor cells and increasing the presence of activated dendritic cells within the tumor microenvironment. In addition, VISTA blockade impaired the suppressive function and reduced the emergence of tumor-specific Foxp3+CD4+ regulatory T cells. Consequently, VISTA mAb administration as a monotherapy significantly suppressed the growth of both transplantable and inducible melanoma. Initial studies explored a combinatorial regimen using VISTA blockade and a peptide-based cancer vaccine with TLR agonists as adjuvants. VISTA blockade synergized with the vaccine to effectively impair the growth of established tumors. Our study therefore establishes a foundation for designing VISTA-targeted approaches either as a monotherapy or in combination with additional immune-targeted strategies for cancer immunotherapy. Cancer Res; 74(7); 1933–44. ©2014 AACR.
IGF-I Regulates Redox Status in Breast Cancer Cells by Activating the Amino Acid Transport Molecule xC−
Authors: Yang Yuzhe , Yee Douglas 
Published: April 2014

AbstractInsulin-like growth factors (IGF) stimulate cell growth in part by increasing amino acid uptake. xCT (SLC7A11) encodes the functional subunit of the cell surface transport system xC−, which mediates cystine uptake, a pivotal step in glutathione synthesis and cellular redox control. In this study, we show that IGF-I regulates cystine uptake and cellular redox status by activating the expression and function of xCT in estrogen receptor-positive (ER+) breast cancer cells by a mechanism that relies on the IGF receptor substrate-1 (IRS-1). Breast cancer cell proliferation mediated by IGF-I was suppressed by attenuating xCT expression or blocking xCT activity with the pharmacologic inhibitor sulfasalazine (SASP). Notably, SASP sensitized breast cancer cells to inhibitors of the type I IGF receptor (IGF-IR) in a manner reversed by the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine. Thus, IGF-I promoted the proliferation of ER+ breast cancer cells by regulating xC− transporter function to protect cancer cells from ROS in an IRS-1–dependent manner. Our findings suggest that inhibiting xC− transporter function may synergize with modalities that target the IGF-IR to heighten their therapeutic effects. Cancer Res; 74(8); 2295–305. ©2014 AACR.
NF-κB Gene Signature Predicts Prostate Cancer Progression
Authors: Jin Renjie , Yi Yajun , Yull Fiona E. , Blackwell Timothy S. , Clark Peter E. , Koyama Tatsuki , Smith Joseph A. , Matusik Robert J. 
Published: April 2014

Abstract
In many patients with prostate cancer, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage prostate cancer would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with prostate cancer progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse prostate cancer model when compared with Hi-Myc alone. Using the nonmalignant NF-κB–activated androgen-depleted mouse prostate, a NF-κB–activated recurrence predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with prostate cancer. This transgenic mouse model–derived gene signature provides a useful and unique molecular profile for human prostate cancer prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery. Cancer Res; 74(10); 2763–72. ©2014 AACR.
SPINK1 Protein Expression and Prostate Cancer Progression
Authors: Flavin Richard , Pettersson Andreas , Hendrickson Whitney K. , Fiorentino Michelangelo , Finn Stephen , Kunz Lauren , Judson Gregory L. , Lis Rosina , Bailey Dyane , Fiore Christopher , Nuttall Elizabeth , Martin Neil E. , Stack Edward , Penney Kathryn L. , Rider Jennifer R. , Sinnott Jennifer , Sweeney Christopher , Sesso Howard D. , Fall Katja , Giovannucci Edward , Kantoff Philip , Stampfer Meir , Loda Massimo , Mucci Lorelei A. 
Published: April 2014

Abstract
Purpose: SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer–specific survival.
Experimental Design: The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983–2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays.
Results: Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P &lt; 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29–1.76).
Conclusions: Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested. Clin Cancer Res; 20(18); 4904–11. ©2014 AACR.
Biomarker Analyses from a Placebo-Controlled Phase II Study Evaluating Erlotinib ± Onartuzumab in Advanced Non–Small Cell Lung Cancer: MET Expression Levels Are Predictive of Patient Benefit
Authors: Koeppen Hartmut , Yu Wei , Zha Jiping , Pandita Ajay , Penuel Elicia , Rangell Linda , Raja Rajiv , Mohan Sankar , Patel Rajesh , Desai Rupal , Fu Ling , Do An , Parab Vaishali , Xia Xiaoling , Januario Tom , Louie Sharianne G. , Filvaroff Ellen , Shames David S. , Wistuba Ignacio , Lipkind Marina , Huang Jenny , Lazarov Mirella , Ramakrishnan Vanitha , Amler Lukas , Phan See-Chun , Patel Premal , Peterson Amy , Yauch Robert L. 
Published: April 2014

Abstract
Purpose: In a recent phase II study of onartuzumab (MetMAb), patients whose non–small cell lung cancer (NSCLC) tissue scored as positive for MET protein by immunohistochemistry (IHC) experienced a significant benefit with onartuzumab plus erlotinib (O+E) versus erlotinib. We describe development and validation of a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers as predictors of patient benefit.
Experimental Design: Biomarkers related to MET and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative reverse transcription PCR, mutation detection techniques, and ELISA.
Results: A positive correlation between IHC, Western blotting, and MET mRNA expression was observed in NSCLC cell lines/tissues. An IHC scoring system of MET expression taking proportional and intensity-based thresholds into consideration was applied in an analysis of the phase II study and resulted in the best differentiation of outcomes. Further analyses revealed a nonsignificant overall survival (OS) improvement with O+E in patients with high MET copy number (mean ≥5 copies/cell by FISH); however, benefit was maintained in “MET IHC-positive”/MET FISH-negative patients (HR, 0.37; P = 0.01). MET, EGFR, amphiregulin, epiregulin, or HGF mRNA expression did not predict a significant benefit with onartuzumab; a nonsignificant OS improvement was observed in patients with high tumor MET mRNA levels (HR, 0.59; P = 0.23). Patients with low baseline plasma hepatocyte growth factor (HGF) exhibited an HR for OS of 0.519 (P = 0.09) in favor of onartuzumab treatment.
Conclusions: MET IHC remains the most robust predictor of OS and progression-free survival benefit from O+E relative to all examined exploratory markers. Clin Cancer Res; 20(17); 4488–98. ©2014 AACR.