bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomised controlled trial of an intervention delivered by app instant messaging to increase the acceptability of effective contraception among young people in Tajikistan: study protocol
Authors: McCarthy Ona , Leurent Baptiste , Edwards Phil , Tokhirov Ravshan , Free Caroline 
Published: September 2017

IntroductionWomen in lower income countries experience unintended pregnancies at a higher rate compared with women in higher income countries. Unintended pregnancy is associated with numerous poorer health outcomes for both women and their children. In Tajikistan, an estimated 26% of married individuals aged 15–24 years have an unmet need for contraception. The strong cultural value placed on childbearing and oppositional attitudes towards contraception are major barriers to contraceptive uptake in the country.Mobile phone ownership is widespread in Tajikistan. The option of receiving reproductive health support on your personal phone may be an appealing alternative to attending a clinic, particularly for young people. The London School of Hygiene & Tropical Medicine and the Tajik Family Planning Association have partnered to develop and evaluate a contraceptive behavioural intervention delivered by mobile phone. The intervention was developed in 2015–2016 guided by behavioural science. It consists of short instant messages sent through an app over 4 months, contains information about contraception and behaviour change methods.Methods and analysisThis randomised controlled trial is designed to evaluate the effect of the intervention on self-reported acceptability of effective contraception at 4 months. 570 men and women aged 16–24 years will be allocated with a ratio of 1:1 to receive the intervention messages or the control messages about trial participation. The messages will be sent through the Tajik Family Planning Association’s ‘healthy lifestyles’ app, which contains basic information about contraception.Ethics and disseminationThe trial was granted ethical approval by the London School of Hygiene & Tropical Medicine Interventions Research Ethics Committee on 16 May 2016 and by the Tajik National Scientific and Research Centre on Paediatrics and Child Surgery on 15 April 2016. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated to study stakeholders.Trial registration numberClinicaltrial.govNCT02905513.Date of registration14 September 2016.WHO trial registration datasethttp://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02905513
Verbal augmented feedback in the rehabilitation of lower extremity musculoskeletal dysfunctions: a systematic review
Authors: Storberget Marianne , Grødahl Linn Helen J , Snodgrass Suzanne , Vliet Paulette van , Heneghan Nicola 
Published: September 2017

BackgroundVerbal augmented feedback (VAF) is commonly used in physiotherapy rehabilitation of individuals with lower extremity musculoskeletal dysfunction or to induce motor learning for injury prevention. Its effectiveness for acquisition, retention and transfer of learning of new skills in this population is unknown.ObjectivesFirst, to investigate the effect of VAF for rehabilitation and prevention of lower extremity musculoskeletal dysfunction. Second, to determine its effect on motor learning and the stages of acquisition, retention and transfer in this population.DesignSystematic review designed in accordance with the Centre for Reviews and Dissemination and reported in line with Preferred Reporting Items for Systematic Review and Meta-analysis.MethodMEDLINE, Embase, PubMed and five additional databases were searched to identify primary studies with a focus on VAF for prevention and rehabilitation of lower extremity musculoskeletal dysfunction. One reviewer screened the titles and abstracts. Two reviewers retrieved full text articles for final inclusion. The first reviewer extracted data, whereas the second reviewer audited. Two reviewers independently assessed risk of bias and quality of evidence using Cochrane Collaboration’s tool and Grading of Recommendations Assessment, Development and Evaluation, respectively.ResultsSix studies were included, with a total sample of 304 participants. Participants included patients with lateral ankle sprain (n=76), postoperative ACL reconstruction (n=16) and healthy individuals in injury prevention (n=212). All six studies included acquisition, whereas retention was found in five studies. Only one study examined transfer of the achieved motor learning (n=36). VAF was found to be effective for improving lower extremity biomechanics and postural control with moderate evidence from five studies.ConclusionVAF should be considered in the rehabilitation of lower extremity musculoskeletal dysfunctions. However, it cannot be unequivocally confirmed that VAF is effective in this population, owing to study heterogeneity and a lack of high-quality evidence. Nevertheless, positive effects on lower extremity biomechanics and postural control have been identified. This suggests that further research into this topic is warranted where an investigation of long-term effects of interventions is required. All stages (acquisition, retention and transfer) should be evaluated.
R-Spondin1/LGR5 Activates TGFβ Signaling and Suppresses Colon Cancer Metastasis
Authors: Zhou Xiaolin , Geng Liying , Wang Degeng , Yi Haowei , Talmon Geoffrey , Wang Jing 
Published: September 2017

Abstract
Leucine-rich repeat containing G-protein–coupled receptor 5 (LGR5), an intestinal stem cell marker, is known to exhibit tumor suppressor activity in colon cancer, the mechanism of which is not understood. Here we show that R-spondin 1 (RSPO1)/LGR5 directly activates TGFβ signaling cooperatively with TGFβ type II receptor in colon cancer cells, enhancing TGFβ-mediated growth inhibition and stress-induced apoptosis. Knockdown of LGR5 attenuated downstream TGFβ signaling and increased cell proliferation, survival, and metastasis in an orthotopic model of colon cancer in vivo. Upon RSPO1 stimulation, LGR5 formed complexes with TGFβ receptors. Studies of patient specimens indicate that LGR5 expression was reduced in advanced stages and positively correlated with markers of TGFβ activation in colon cancer. Our study uncovers a novel cross-talk between LGR5 and TGFβ signaling in colon cancer and identifies LGR5 as a new modulator of TGFβ signaling able to suppress colon cancer metastasis. Cancer Res; 77(23); 6589–602. ©2017 AACR.
Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease
Authors: Lu Donghao , Carlsson Jessica , Penney Kathryn L. , Davidsson Sabina , Andersson Swen-Olof , Mucci Lorelei A. , Valdimarsdóttir Unnur , Andrén Ove , Fang Fang , Fall Katja 
Published: September 2017

Abstract
Background: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared with men with nonlethal disease.
Methods: On the basis of the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through transurethral resection of the prostate during 1977–1998 with follow-up up to 30 years. For those with tumor tissue (N = 262), we measured mRNA expression of 223 selected genes included in neuroendocrine pathways. Using DNA from normal prostate tissue (N = 396), we genotyped 36 SNPs from 14 receptor genes. Lethal prostate cancer was the primary outcome in analyses with pathway gene expression and genetic variants.
Results: Differential expression of genes in the serotoninergic pathway was associated with risk of lethal prostate cancer (P = 0.007); similar but weaker associations were noted for the adrenergic (P = 0.014) and glucocorticoid (P = 0.020) pathways. Variants of the HTR2A (rs2296972; P = 0.002) and NR3CI (rs33388; P = 0.035) genes (within the serotoninergic and glucocorticoid pathways) were associated with lethal cancer in overdominant models. These genetic variants were correlated with expression of several genes in corresponding pathways (P &lt; 0.05).
Conclusions: Our findings lend support to hypothesis that the neuroendocrine pathways, particularly serotoninergic pathway, are associated with lethal outcome in the natural course of localized prostate cancer.
Impact: This study provides evidence of the role of neuroendocrine pathways in prostate cancer progression that may have clinical utility. Cancer Epidemiol Biomarkers Prev; 26(12); 1781–7. ©2017 AACR.
A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma
Authors: Federico Sara M. , McCarville M. Beth , Shulkin Barry L. , Sondel Paul M. , Hank Jacquelyn A. , Hutson Paul , Meagher Michael , Shafer Aaron , Ng Catherine Y. , Leung Wing , Janssen William E. , Wu Jianrong , Mao Shenghua , Brennan Rachel C. , Santana Victor M. , Pappo Alberto S. , Furman Wayne L. 
Published: September 2017

Abstract
Purpose: Anti-GD2 mAbs, acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines, and haploidentical natural killer (NK) cells.
Experimental Design: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40 mg/m2/dose, days 2–5), GM-CSF, and IL2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4), and ifosfamide/carboplatin/etoposide (courses 5,6). Parentally derived NK cells were administered with courses 2, 4, and 6. Serum for pharmacokinetic studies of hu14.18K322A, soluble IL2 receptor alpha (sIL2Rα) levels, and human antihuman antibodies (HAHA) were obtained.
Results: Thirteen heavily pretreated patients (9 with prior anti-GD2 therapy) completed 65 courses. One patient developed an unacceptable toxicity (grade 4 thrombocytopenia &gt;35 days). Four patients discontinued treatment for adverse events (hu14.18K322A allergic reaction, viral infection, surgical death, second malignancy). Common toxicities included grade 3/4 myelosuppression (13/13 patients) and grade 1/2 pain (13/13 patients). Eleven patients received 29 NK-cell infusions. The response rate was 61.5% (4 complete responses, 1 very good partial response, 3 partial responses) and five had stable disease. The median time to progression was 274 days (range, 239–568 days); 10 of 13 patients (77%) survived 1 year. Hu14.18K322A pharmacokinetics was not affected by chemotherapy or HAHA. All patients had increased sIL2Rα levels, indicating immune activation.
Conclusions: Chemotherapy plus hu14.18K322A, cytokines, and NK cells is feasible and resulted in clinically meaningful responses in patients with refractory/recurrent neuroblastoma. Further studies of this approach are warranted in patients with relapsed and newly diagnosed neuroblastoma. Clin Cancer Res; 23(21); 6441–9. ©2017 AACR.
Radiomics Analysis for Evaluation of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
Authors: Liu Zhenyu , Zhang Xiao-Yan , Shi Yan-Jie , Wang Lin , Zhu Hai-Tao , Tang Zhenchao , Wang Shuo , Li Xiao-Ting , Tian Jie , Sun Ying-Shi 
Published: September 2017

Abstract
Purpose: To develop and validate a radiomics model for evaluating pathologic complete response (pCR) to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC).
Experimental Design: We enrolled 222 patients (152 in the primary cohort and 70 in the validation cohort) with clinicopathologically confirmed LARC who received chemoradiotherapy before surgery. All patients underwent T2-weighted and diffusion-weighted imaging before and after chemoradiotherapy; 2,252 radiomic features were extracted from each patient before and after treatment imaging. The two-sample t test and the least absolute shrinkage and selection operator regression were used for feature selection, whereupon a radiomics signature was built with support vector machines. Multivariable logistic regression analysis was then used to develop a radiomics model incorporating the radiomics signature and independent clinicopathologic risk factors. The performance of the radiomics model was assessed by its calibration, discrimination, and clinical usefulness with independent validation.
Results: The radiomics signature comprised 30 selected features and showed good discrimination performance in both the primary and validation cohorts. The individualized radiomics model, which incorporated the radiomics signature and tumor length, also showed good discrimination, with an area under the receiver operating characteristic curve of 0.9756 (95% confidence interval, 0.9185–0.9711) in the validation cohort, and good calibration. Decision curve analysis confirmed the clinical utility of the radiomics model.
Conclusions: Using pre- and posttreatment MRI data, we developed a radiomics model with excellent performance for individualized, noninvasive prediction of pCR. This model may be used to identify LARC patients who can omit surgery after chemoradiotherapy. Clin Cancer Res; 23(23); 7253–62. ©2017 AACR.
In-depth Genetic Analysis of Sclerosing Epithelioid Fibrosarcoma Reveals Recurrent Genomic Alterations and Potential Treatment Targets
Authors: Arbajian Elsa , Puls Florian , Antonescu Cristina R. , Amary Fernanda , Sciot Raf , Debiec-Rychter Maria , Sumathi Vaiyapuri P. , Järås Marcus , Magnusson Linda , Nilsson Jenny , Hofvander Jakob , Mertens Fredrik 
Published: September 2017

Abstract
Purpose: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid sarcoma (LGFMS). Some tumors display morphologic characteristics of both SEF and LGFMS, hence they are known as hybrid SEF/LGFMS. Despite the overlap of gene fusion variants between these two tumor types, SEF is much more aggressive. The current study aimed to further characterize SEF and hybrid SEF/LGFMS genetically to better understand the role of the characteristic fusion genes and possible additional genetic alterations in tumorigenesis.
Experimental Design: We performed whole-exome sequencing, SNP array analysis, RNA sequencing (RNA-seq), global gene expression analyses, and/or IHC on a series of 13 SEFs and 6 hybrid SEF/LGFMS. We also expressed the FUS-CREB3L2 and EWSR1-CREB3L1 fusion genes conditionally in a fibroblast cell line; these cells were subsequently analyzed by RNA-seq, and expression of the CD24 protein was assessed by FACS analysis.
Results: The SNP array analysis detected a large number of structural aberrations in SEF and SEF/LGFMS, many of which were recurrent, notably DMD microdeletions. RNA-seq identified FUS-CREM and PAX5-CREB3L1 as alternative fusion genes in one SEF each. CD24 was strongly upregulated, presumably a direct target of the fusion proteins. This was further confirmed by the gene expression analysis and FACS analysis on Tet-On 3G cells expressing EWSR1-CREB3L1.
Conclusions: Although gene fusions are the primary tumorigenic events in both SEF and LGFMS, additional genomic changes explain the differences in aggressiveness and clinical outcome between the two types. CD24 and DMD constitute potential therapeutic targets. Clin Cancer Res; 23(23); 7426–34. ©2017 AACR.
ABC294640, A Novel Sphingosine Kinase 2 Inhibitor, Induces Oncogenic Virus–Infected Cell Autophagic Death and Represses Tumor Growth
Authors: Dai Lu , Bai Aiping , Smith Charles D. , Rodriguez Paulo C. , Yu Fangyou , Qin Zhiqiang 
Published: September 2017

Abstract
Kaposi sarcoma–associated herpes virus (KSHV) is the etiologic agent of several malignancies, including Kaposi sarcoma and primary effusion lymphoma (PEL), which preferentially arise in HIV+ patients and lack effective treatment. Sphingosine kinase 2 (SphK2) is a key factor within sphingolipid metabolism, responsible for the conversion of proapoptotic ceramides to antiapoptotic sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to the accumulation of intracellular ceramides and induces apoptosis in KSHV-infected primary endothelial cells and PEL tumor cells but not in uninfected cells. In this study, we found that ABC294640 induces autophagic death instead of apoptosis in a KSHV long-term–infected immortalized endothelial cell-line, TIVE-LTC, but not in uninfected TIVE cells, through the upregulation of LC3B protein. Transcriptomic analysis indicates that many genes related to cellular stress responses, cell cycle/proliferation, and cellular metabolic process are altered in TIVE-LTC exposed to ABC294640. One of the candidates, Egr-1, was found to directly regulate LC3B expression and was required for the ABC294640-induced autophagic death. By using a Kaposi sarcoma–like nude mice model with TIVE-LTC, we found that ABC294640 treatment significantly suppressed KSHV-induced tumor growth in vivo, which indicates that targeting sphingolipid metabolism, especially SphK2, may represent a promising therapeutic strategy against KSHV-related malignancies. Mol Cancer Ther; 16(12); 2724–34. ©2017 AACR.
Obesity, Treatment Times, and Cardiovascular Outcomes After ST‐Elevation Myocardial Infarction: Findings From Mission: Lifeline North Texas
Authors: Champagne‐Langabeer Tiffany , Kim Junghyun , Bower Julie K. , Gardner Angela , Fowler Raymond , Langabeer James R. 
Published: September 2017

Background
With increasing rates of obesity and its link with cardiovascular disease, there is a need for better understanding of the obesity‐outcome relationship. This study explores the association between categories of obesity with treatment times and mortality for patients experiencing ST‐segment elevation myocardial infarction.

Methods and Results
We examined 8725 patients with ST‐segment elevation myocardial infarction who underwent primary percutaneous coronary intervention and used regression models to analyze the relationship between 6 categories of body mass index with key door‐to‐balloon time, total ischemic time, and in‐hospital mortality. We relied on data from the Mission: Lifeline North Texas program, consisting of 33 percutaneous coronary intervention–capable hospitals in 6 counties surrounding Dallas, Texas. Data were extracted from the National Cardiovascular Data Registry for each participating hospital. Of the samples, 76% were overweight or obese. Comparing the univariate differences between the normal‐weight group and the pooled sample, we observed a U‐shaped association between body mass index and both mortality and door‐to‐balloon times. The most underweight and severely obese had the highest mortality and median door‐to‐balloon time, respectively. These differences persisted after multivariate adjustments for door‐to‐balloon time, but not for mortality.

Conclusions
Extremely obese patients have longer treatment time delays than other body mass index categories. However, this did not extend to significant differences in mortality in the multivariate models. We conclude that clinicians should incorporate body mass assessments into their diagnosis and treatment plans to mitigate observed disparities.
Association Between Troponin Levels and Embolic Stroke of Undetermined Source
Authors: Merkler Alexander E. , Gialdini Gino , Murthy Santosh B. , Salehi Omran Setareh , Moya Antonio , Lerario Michael P. , Chong Ji , Okin Peter M. , Weinsaft Jonathan W. , Safford Monika M. , Fink Matthew E. , Navi Babak B. , Iadecola Costantino , Kamel Hooman 
Published: September 2017

Background

Our aim was to determine whether patients with embolic strokes of undetermined source (
ESUS
) have higher rates of elevated troponin than patients with noncardioembolic strokes.

Methods and Results

CAESAR (The Cornell Acute Stroke Academic Registry) prospectively enrolled all adults with acute stroke from 2011 to 2014. Two neurologists used standard definitions to retrospectively ascertain the etiology of stroke, with a third resolving disagreements. In this analysis we included patients with
ESUS
and, as controls, patients with small‐ and large‐artery strokes; only patients with a troponin measured within 24 hours of stroke onset were included. A troponin elevation was defined as a value exceeding our laboratory's upper limit (0.04 ng/mL) without a clinically recognized acute
ST
‐segment elevation myocardial infarction. Multiple logistic regression was used to evaluate the association between troponin elevation and
ESUS
after adjustment for demographics, stroke severity, insular infarction, and vascular risk factors. In a sensitivity analysis we excluded patients diagnosed with atrial fibrillation after discharge. Among 512 patients, 243 (47.5%) had
ESUS
, and 269 (52.5%) had small‐ or large‐artery stroke. In multivariable analysis an elevated troponin was independently associated with
ESUS
(odds ratio 3.3; 95% confidence interval 1.2, 8.8). This result was unchanged after excluding patients diagnosed with atrial fibrillation after discharge (odds ratio 3.4; 95% confidence interval 1.3, 9.1), and the association remained significant when troponin was considered a continuous variable (odds ratio for log[troponin], 1.4; 95% confidence interval 1.1, 1.7).

Conclusions

Elevations in cardiac troponin are more common in patients with
ESUS
than in those with noncardioembolic strokes.