bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensorimotor Incongruence in People with Musculoskeletal Pain: A Systematic Review
Authors: Don Sanneke , Voogt Lennard , Meeus Mira , De Kooning Margot , Nijs Jo 
Published: May 2016

AbstractObjectivesMusculoskeletal pain has major public health implications, but the theoretical framework remains unclear. It is hypothesized that sensorimotor incongruence (SMI) might be a cause of long‐lasting pain sensations in people with chronic musculoskeletal pain. Research data about experimental SMI triggering pain has been equivocal, making the relation between SMI and pain elusive. The aim of this study was to systematically review the studies on experimental SMI in people with musculoskeletal pain and healthy individuals.MethodsPreferred reporting items for systematic reviews and meta‐analyses guidelines were followed. A systematic literature search was conducted using several databases until January 2015. To identify relevant articles, keywords regarding musculoskeletal pain or healthy subjects and the sensory or the motor system were combined. Study characteristics were extracted. Risk of bias was assessed using the Dutch Institute for Healthcare Improvement (CBO) checklist for randomized controlled trials, and level of evidence was judged.ResultsEight cross‐over studies met the inclusion criteria. The methodological quality of the studies varied, and populations were heterogeneous. In populations with musculoskeletal pain, outcomes of sensory disturbances and pain were higher during all experimental conditions compared to baseline conditions. In healthy subjects, pain reports during experimental SMI were very low or did not occur at all.DiscussionBased on the current evidence and despite some methodological issues, there is no evidence that experimental SMI triggers pain in healthy individuals and in people with chronic musculoskeletal pain. However, people with chronic musculoskeletal pain report more sensory disturbances and pain during the experimental conditions, indicating that visual manipulation influences pain outcomes in this population.
Low-Level Laser Therapy for Chronic Non-Specific Low Back Pain: A Meta-Analysis of Randomised Controlled Trials
Authors: Glazov Gregory , Yelland Michael , Emery Jon 
Published: May 2016

Objective The efficacy of low-level laser treatment (LLLT) for chronic back pain remains controversial due to insufficient trial data. We aimed to conduct an updated review to determine if LLLT (including laser acupuncture) has specific benefits in chronic non-specific low back pain (CNLBP). Methods Electronic databases were searched for randomised trials using sham controls and blinded assessment examining the intervention of LLLT in adults with CNLBP. Primary outcomes were pain and global assessment of improvement with up to short-term follow-up. Secondary outcomes were disability, range of back movement, and adverse effects. A random effects meta-analysis was conducted. Subgroup analyses were based on laser dose, duration of baseline pain, and whether or not laser therapy used an acupuncture approach. Results 15 studies were selected involving 1039 participants. At immediate and short-term follow-up there was significant pain reduction of up to WMD (weighted mean difference) −1.40 cm (95% CI −1.91 to −0.88 cm) in favour of laser treatment, occurring in trials using at least 3 Joules (J) per point, with baseline pain <30 months and in non-acupuncture LLLT trials. Global assessment showed a risk ratio of 2.16 (95% CI 1.61 to 2.90) in favour of laser treatment in the same groups only at immediate follow-up. Conclusions We demonstrated moderate quality of evidence (GRADE) to support a clinically important benefit in LLLT for CNLBP in the short term, which was only seen following higher laser dose interventions and in participants with a shorter duration of back pain. Rigorously blinded trials using appropriate laser dosage would provide greater certainty around this conclusion.
Formative research to develop theory-based messages for a Western Australian child drowning prevention television campaign: study protocol
Authors: Denehy Mel , Crawford Gemma , Leavy Justine , Nimmo Lauren , Jancey Jonine 
Published: May 2016

IntroductionWorldwide, children under the age of 5 years are at particular risk of drowning. Responding to this need requires the development of evidence-informed drowning prevention strategies. Historically, drowning prevention strategies have included denying access, learning survival skills and providing supervision, as well as education and information which includes the use of mass media. Interventions underpinned by behavioural theory and formative evaluation tend to be more effective, yet few practical examples exist in the drowning and/or injury prevention literature. The Health Belief Model and Social Cognitive Theory will be used to explore participants' perspectives regarding proposed mass media messaging. This paper describes a qualitative protocol to undertake formative research to develop theory-based messages for a child drowning prevention campaign.Methods and analysisThe primary data source will be focus group interviews with parents and caregivers of children under 5 years of age in metropolitan and regional Western Australia. Qualitative content analysis will be used to analyse the data.Ethics and disseminationThis study will contribute to the drowning prevention literature to inform the development of future child drowning prevention mass media campaigns. Findings from the study will be disseminated to practitioners, policymakers and researchers via international conferences, peer and non-peer-reviewed journals and evidence summaries. The study was submitted and approved by the Curtin University Human Research Ethics Committee.
Nipple sparing versus skin sparing mastectomy: a systematic review protocol
Authors: Agha Riaz A , Wellstead Georgina , Sagoo Harkiran , Al Omran Yasser , Barai Ishani , Rajmohan Shivanchan , Fowler Alexander J , Orgill Dennis P , Rusby Jennifer E 
Published: May 2016

IntroductionBreast cancer has a lifetime incidence of one in eight women. Over the past three decades there has been a move towards breast conservation and a focus on aesthetic outcomes while maintaining oncological safety. For some patients, mastectomy is the preferred option. There is growing interest in the potential use of nipple sparing mastectomy (NSM). However, oncological safety remains unproven, and the benefits and indications have not been clearly identified. The objective of this systematic review will be to determine the safety and efficacy of NSM as compared with skin sparing mastectomy (SSM).Methods and analysisAll original comparative studies including; randomised controlled trials, cohort studies and case–control studies involving women undergoing either NSM or SSM for breast cancer will be included. Outcomes are primary—relating to oncological outcomes and secondary—relating to clinical, aesthetic, patient reported and quality of life outcomes. A comprehensive electronic literature search, designed by a search specialist, will be undertaken. Grey literature searches will also be conducted. Eligibility assessment will occur in two stages; title and abstract screening and then full text assessment. Each step will be conducted by two trained teams acting independently. Data will then be extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry. Data analysis will be undertaken to explore the relationship between NSM or SSM and preselected outcomes, heterogeneity will be assessed using the Cochrane tests.Ethics and disseminationThis systematic review requires no ethical approval. It will be published in a peer-reviewed journal. It will also be presented at national and international conferences. Updates of the review will be conducted to inform and guide healthcare practice and policy.
Evaluation of the optimal provision of formalin-fixed, paraffin-embedded material for reverse transcription-PCR in soft-tissue tumour diagnosis
Authors: Thway Khin , Wren Dorte , Lee Jasmin , Thompson Lisa , Fisher Cyril , Gonzalez David 
Published: May 2016

AimsMolecular genetic analysis is now a routine ancillary diagnostic modality to the histopathological diagnosis of soft-tissue neoplasms, many of which harbour characteristic gene fusions detectable by reverse transcription-PCR (RT-PCR). As the final diagnosis often depends on the molecular result, it is important to obtain the optimal yield of patient RNA.MethodsWe assessed the most reliable method of providing formalin-fixed, paraffin-embedded material for optimal RNA yield by comparing three consecutive periods in which different preparations (5×10 μm scrolls, 5×5 μm sections and 1×10 μm sections) were used for RNA extraction for RT-PCR, with its technical success rate.ResultsFor ‘2011’, ‘2012’ and ‘2013’, RT-PCR technical failure rates were 13.4%, 4.4% and 7.9%, respectively. The percentage of failed referral cases was 71.4%, 85.7% and 31.3%, and the proportion of core biopsy to excision specimens was 3:15, 2:5 and 13:3.ConclusionsThis study shows that the effectiveness of RNA extraction and purification is dependent on both specimen type and the tissue sectioning strategy. The failure rate has improved over recent years, particularly for large specimens as large numbers of thick 10 μm scrolls can saturate RNA extraction columns. In contrast, recent technical fails are more frequent in core biopsies, where 1×10 μm sections are insufficient for adequate RNA extraction. While previous technical fails occurred mostly in referred cases, this appears no longer the case due to the better fixation and processing of specimens in external surgical pathology departments because of the widespread recognition of the importance of molecular diagnostics as an important part of the patient pathway.
Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel
Authors: Liu Xianzhe , Gao Yan , Shen Jacson , Yang Wen , Choy Edwin , Mankin Henry , Hornicek Francis J. , Duan Zhenfeng 
Published: May 2016

Abstract
Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNAi-mediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients. Mol Cancer Ther; 15(7); 1691–701. ©2016 AACR.
Combining ABCG2 Inhibitors with IMMU-132, an Anti–Trop-2 Antibody Conjugate of SN-38, Overcomes Resistance to SN-38 in Breast and Gastric Cancers
Authors: Chang Chien-Hsing , Wang Yang , Zalath Maria , Liu Donglin , Cardillo Thomas M. , Goldenberg David M. 
Published: May 2016

Abstract
Sacituzumab govitecan (IMMU-132), an SN-38–conjugated antibody–drug conjugate, is showing promising therapeutic results in a phase I/II trial of patients with advanced Trop-2–expressing, metastatic, solid cancers. As members of the ATP-binding cassette (ABC) transporters confer chemotherapy resistance by active drug efflux, which is a frequent cause of treatment failure, we explored the use of known inhibitors of ABC transporters for improving the therapeutic efficacy of IMMU-132 by overcoming SN-38 resistance. Two human tumor cell lines made resistant to SN-38, MDA-MB-231-S120 (human breast cancer) and NCI-N87-S120 (human gastric cancer), were established by continuous exposure of the parental cells to stepwise increased concentrations of SN-38 and analyzed by flow cytometry for functional activities of ABCG2 and ABCB1, immunoblotting and qRT-PCR for the expression of ABCG2 at both protein and mRNA levels, and MTS assays for the potency of SN-38 alone or in combination with a modulator of ABC transporters. MDA-MB-231-S120 and NCI-N87-S120 displayed reduced sensitivity to SN-38 in vitro, with IC50 values approximately 50-fold higher than parental MDA-MB-231 and NCI-N87 cells. The increase in drug resistance of both S120 cell populations is associated with the expression of functional ABCG2, but not ABCB1. Importantly, treatment of both S120 sublines with known ABCG2 inhibitors (fumitremorgin C, Ko143, and YHO-13351) restored toxicity of SN-38, and the combination of YHO-13351 with IMMU-132 increased the median survival of mice bearing NCI-N87-S120 xenografts. These results provide a rationale for combination therapy of IMMU-132 and inhibitors of ABC transporters, such as YHO-13351. Mol Cancer Ther; 15(8); 1910–9. ©2016 AACR.
Helical Centerline Stent Improves Patency
Authors: Zeller Thomas , Gaines Peter A. , Ansel Gary M. , Caro Colin G. 
Published: May 2016

Background—
Reintervention in the femoropopliteal artery is frequent and a major driver of cost-effectiveness. High wall shear generated by swirling blood flow is associated with reduced occurrence of atherosclerosis and restenosis. This trial investigated the clinical and hemodynamic outcomes of the BioMimics 3D self-expanding tubular nitinol stent with helical centerline geometry compared with a straight stent in the femoropopliteal artery.

Methods and Results—

In a prospective, multicenter, randomized controlled trial, 76 patients with symptomatic peripheral arterial disease were randomized 2:1 to receive a helical or a straight stent. An independent core laboratory adjudicated angiographic and ultrasound parameters. The primary safety end point was freedom from a composite of all death, target limb amputation, and target lesion revascularization at 30 days. The primary effectiveness end point was freedom from clinically driven target lesion revascularization at 6 months. Patency was a secondary end point. Subjects were followed up for 2 years from intervention. The primary safety (1-sided
P
<0.01) and efficacy (1-sided
P
<0.001) end points for the helical stent were met. The proportion of patients treated with the helical stent who maintained patency at 12 and 24 months was 80% and 72%, respectively, compared with 71% and 55% for the control group. The difference was significant through 24 months (
P
=0.05). Freedom from clinically driven target lesion revascularization for the helical compared with straight stent was 91% versus 92% at 12 months and 91% versus 76% at 24 months.

Conclusions—
Both groups had similar safety outcomes and clinically driven target lesion revascularization to 2 years. However, after placement of a BioMimics 3D helical stent, there was improved patency to 2 years.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02163863.
Multimarker Risk Stratification in Patients With Acute Myocardial Infarction
Authors: O'Donoghue Michelle L. , Morrow David A. , Cannon Christopher P. , Jarolim Petr , Desai Nihar R. , Sherwood Matthew W. , Murphy Sabina A. , Gerszten Robert E. , Sabatine Marc S. 
Published: May 2016

Background

Several biomarkers have individually been shown to be useful for risk stratification in patients with acute myocardial infarction (
MI
). The optimal multimarker strategy remains undefined.

Methods and Results

Biomarkers representing different pathobiological axes were studied, including myocardial stress/structural changes (
NT
‐pro B‐type natriuretic peptide [
NT
‐pro
BNP
], midregional proatrial natriuretic peptide [
MR
‐pro
ANP
], suppression of tumorigenicity 2 [
ST
2], galectin‐3, midregional proadrenomedullin [
MR
‐pro
ADM
], and copeptin), myonecrosis (troponin T), and inflammation (myeloperoxidase [
MPO
], high sensitivity C‐reactive protein [hs
CRP
], pregnancy‐associated plasma protein A [
PAPP
‐A], and growth‐differentiation factor‐15 [
GDF
‐15]), in up to 1258 patients from Clopidogrel as Adjunctive Reperfusion Therapy‐Thrombolysis in Myocardial Infarction 28 (
CLARITY
‐
TIMI
28), a randomized trial of clopidogrel in
ST
‐elevation
MI
(
STEMI
). Patients were followed for 30 days. Biomarker analyses were adjusted for traditional clinical variables. Forward step‐wise selection was used to assess a multimarker strategy. After adjustment for clinical variables and using a dichotomous cutpoint, 7 biomarkers were each significantly associated with a higher odds of cardiovascular death or heart failure (
HF
) through 30 days, including
NT
‐pro
BNP
(adjusted odds ratio [
OR
adj
], 2.54; 95%
CI
, 1.47–4.37),
MR
‐pro
ANP
(2.18; 1.27–3.76),
ST
2 (2.88; 1.72–4.81), troponin T (4.13; 1.85–9.20),
MPO
(2.75; 1.20–6.27), hs
CRP
(1.96, 1.17–3.30), and
PAPP
‐A (3.04; 1.17–7.88). In a multimarker model, 3 biomarkers emerged as significant and complementary predictors of cardiovascular death or
HF
:
ST
2 (
OR
adj
, 2.87; 1.61–5.12), troponin T (2.34; 1.09–5.01 and 4.13, 1.85–9.20, respectively for intermediate and high levels), and
MPO
(2.49; 1.04–5.96). When added to the
TIMI STEMI
Risk Score alone, the multimarker risk score significantly improved the C‐statistic (area under the curve, 0.75 [95%
CI
, 0.69–0.81] to 0.82 [0.78–0.87];
P
=0.001), net reclassification index (0.93;
P
<0.001), and integrated discrimination index (0.09;
P
<0.001).

Conclusions

In patients with
STEMI
, a multimarker strategy that combines biomarkers across pathobiological axes of myocardial stress, myocyte necrosis, and inflammation provides incremental prognostic information for prediction of cardiovascular death or
HF
.
Dairy Consumption and Risk of Stroke: A Systematic Review and Updated Dose–Response Meta‐Analysis of Prospective Cohort Studies
Authors: de Goede Janette , Soedamah‐Muthu Sabita S. , Pan An , Gijsbers Lieke , Geleijnse Johanna M. 
Published: May 2016

Background
A higher milk consumption may be associated with a lower stroke risk. We conducted a comprehensive systematic review and dose–response meta‐analysis of milk and other dairy products in relation to stroke risk.

Methods and Results

Through a systematic literature search, prospective cohort studies of dairy foods and incident stroke in stroke‐free adults were identified. Random‐effects meta‐analyses with summarized dose–response data were performed, taking into account sources of heterogeneity, and spline models were used to systematically investigate nonlinearity of the associations. We included 18 studies with 8 to 26 years of follow‐up that included 762 414 individuals and 29 943 stroke events. An increment of 200 g of daily milk intake was associated with a 7% lower risk of stroke (relative risk 0.93; 95%
CI
0.88–0.98;
P
=0.004; I
2
=86%). Relative risks were 0.82 (95%
CI
0.75–0.90) in East Asian and 0.98 (95%
CI
0.95–1.01) in Western countries (median intakes 38 and 266 g/day, respectively) with less but still considerable heterogeneity within the continents. Cheese intake was marginally inversely associated with stroke risk (relative risk 0.97; 95%
CI
0.94–1.01 per 40 g/day). Risk reductions were maximal around 125 g/day for milk and from 25 g/day onwards for cheese. Based on a limited number of studies, high‐fat milk was directly associated with stroke risk. No associations were found for yogurt, butter, or total dairy.

Conclusions
Milk and cheese consumption were inversely associated with stroke risk. Results should be placed in the context of the observed heterogeneity. Future epidemiological studies should provide more details about dairy types, including fat content. In addition, the role of dairy in Asian populations deserves further attention.
Sphingosine‐1‐Phosphate Receptor 1 Regulates Cardiac Function by Modulating Ca
2+
Sensitivity and Na
+
/H
+
Exchange and Mediates Protection by Ischemic Preconditioning
Authors: Keul Petra , van Borren Marcel M. G. J. , Ghanem Alexander , Müller Frank Ulrich , Baartscheer Antonius , Verkerk Arie O. , Stümpel Frank , Schulte Jan Sebastian , Hamdani Nazha , Linke Wolfgang A. , van Loenen Pieter , Matus Marek , Schmitz Wilhelm , Stypmann Jörg , Tiemann Klaus , Ravesloot Jan‐Hindrik , Alewijnse Astrid E. , Hermann Sven , Spijkers Léon J. A. , Hiller Karl‐Heinz , Herr Deron , Heusch Gerd , Schäfers Michael , Peters Stephan L. M. , Chun Jerold , Levkau Bodo 
Published: May 2016

Background

Sphingosine‐1‐phosphate plays vital roles in cardiomyocyte physiology, myocardial ischemia–reperfusion injury, and ischemic preconditioning. The function of the cardiomyocyte sphingosine‐1‐phosphate receptor 1 (S1P
1
) in vivo is unknown.

Methods and Results

Cardiomyocyte‐restricted deletion of S1P
1
in mice (S1P
1
α

MHCC

re
) resulted in progressive cardiomyopathy, compromised response to dobutamine, and premature death. Isolated cardiomyocytes from S1P
1
α

MHCC

re
mice revealed reduced diastolic and systolic Ca
2+
concentrations that were secondary to reduced intracellular Na
+
and caused by suppressed activity of the sarcolemmal Na
+
/H
+
exchanger
NHE
‐1 in the absence of S1P
1
. This scenario was successfully reproduced in wild‐type cardiomyocytes by pharmacological inhibition of S1P
1
or sphingosine kinases. Furthermore, Sarcomere shortening of S1P
1
α

MHCC

re
cardiomyocytes was intact, but sarcomere relaxation was attenuated and Ca
2+
sensitivity increased, respectively. This went along with reduced phosphorylation of regulatory myofilament proteins such as myosin light chain 2, myosin‐binding protein C, and troponin I. In addition, S1P
1
mediated the inhibitory effect of exogenous sphingosine‐1‐phosphate on β‐adrenergic–induced cardiomyocyte contractility by inhibiting the adenylate cyclase. Furthermore, ischemic precondtioning was abolished in S1P
1
α

MHCC

re
mice and was accompanied by defective Akt activation during preconditioning.

Conclusions

Tonic S1P
1
signaling by endogenous sphingosine‐1‐phosphate contributes to intracellular Ca
2+
homeostasis by maintaining basal
NHE
‐1 activity and controls simultaneously myofibril Ca
2+
sensitivity through its inhibitory effect on adenylate cyclase. Cardioprotection by ischemic precondtioning depends on intact S1P
1
signaling. These key findings on S1P
1
functions in cardiac physiology may offer novel therapeutic approaches to cardiac diseases.
High Risk of Venous Thromboembolism in Klinefelter Syndrome
Authors: Zöller Bengt , Ji Jianguang , Sundquist Jan , Sundquist Kristina 
Published: May 2016

Background

Klinefelter syndrome (
KS
) is the most common sex chromosome disorder. The genetic background is the extra X chromosome. Venous thromboembolism (
VTE
) has been observed among
KS
patients. The aim of the present study was to examine whether
KS
is associated with
VTE
.

Methods and Results

We followed up all hospital in‐ and outpatients (N=1085) in Sweden with a diagnosis of
KS
between January 1, 1969, and December 31, 2010, for diagnosis of
VTE
. The reference population was the total male populace of Sweden. We calculated standardized incidence ratios for
VTE
, adjusted for age, sex, education, time period, and region of residence. The standardized incidence ratio for
KS
was 6.43 (95% CI 5.15–7.93), with the highest ratio observed at young age. The standardized incidence ratios for
VTE
were 12.10 (95%
CI
6.22–21.21) before age 30 years, 11.00 (95% CI 7.86–14.99) between ages 30 and 49 years, 4.83 (95% CI 3.23–6.95) between ages 50 and 69 years, and 2.07 (95% CI 0.74–4.53) for ages ≥70 years. The cumulative incidence of
VTE
for
KS
patients was 8.6% at age 50 years and 20.8% at age 70 years.

Conclusions

KS is associated with high risk of VTE. KS could be considered a genetic hypercoagulable state. This has clinical implications for the prevention and diagnosis of
VTE
among patients with KS.