bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point-of-care lung ultrasound in young children with respiratory tract infections and wheeze
Authors: Varshney Terry , Mok Elise , Shapiro Adam J , Li Patricia , Dubrovsky Alexander S 
Published: April 2016

ObjectiveCharacterise lung ultrasound (LUS) findings, diagnostic accuracy and agreement between novice and expert interpretations in young children with respiratory tract infections and wheeze.MethodsProspective cross-sectional study in a paediatric ED. Patients ≤2 years with a respiratory tract infection and wheeze at triage were recruited unless in severe respiratory distress. Prior to clinical management, a novice sonologist performed the LUS using a six-zone scanning protocol. The treating physician remained blinded to ultrasound findings; final diagnoses were extracted from the medical record. An expert sonologist, blinded to all clinical information, assessed the ultrasound video clips at study completion. Positive LUS was defined as the presence of ≥1 of the following findings: ≥3 B-lines per intercostal space, consolidation and/or pleural abnormalities.ResultsNinety-four patients were enrolled (median age 11.1 months). LUS was positive in 42% (39/94) of patients (multiple B-lines in 80%, consolidation in 64%, pleural abnormalities in 23%). The proportion of positive LUS, along with their diagnostic accuracy (sensitivity (95% CI), specificity (95% CI)), were as follows for children with bronchiolitis, asthma, pneumonia and asthma/pneumonia: 46% (45.8% (34.0% to 58.0%), 72.7% (49.8% to 89.3%)), 0% (0% (0.0% to 23.3%), 51.3% (39.8% to 62.6%)), 100% (100% (39.8% to 100.0%), 61.1% (50.3% to 71.2%)), 50% (50% (6.8% to 93.2%), 58.9% (48.0% to 69.2%)), respectively. There was good agreement between the novice and expert sonographers for a positive LUS (kappa 0.68 (95% CI 0.54 to 0.82)).ConclusionsAmong children with respiratory tract infections and wheeze, a positive LUS seems to distinguish between clinical syndromes by ruling in pneumonia and ruling out asthma. If confirmed in future studies, LUS may emerge as a point-of-care tool to guide diagnosis and disposition in young children with wheeze.
ASPECTS decay during inter-facility transfer in patients with large vessel occlusion strokes
Authors: Mokin Maxim , Gupta Rishi , Guerrero Waldo R , Rose David Z , Burgin William S , Sivakanthan Sananthan 
Published: April 2016

BackgroundFavorable imaging profile according to the Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast head CT is a key criterion for the selection of patients with ischemic stroke from large vessel occlusion (LVO) for IA revascularization therapies.ObjectiveTo analyze factors associated with changes in ASPECTS during inter-hospital transfer and to determine how deterioration of ASPECTS affects eligibility for endovascular procedures.MethodsWe analyzed factors associated with changes in ASPECTS during inter-hospital transfer and their potential impact on eligibility for IA stroke therapies in patients with anterior circulation ischemic strokes. Clinical and demographic characteristics between patients with favorable (ASPECTS ≥6) and unfavorable (ASPECTS <6) imaging on repeat CT were compared.ResultsStroke evolution towards unfavorable ASPECTS occurred in 13/42 (31%) patients who initially had a favorable imaging profile at outside hospitals. A higher National Institutes of Health Stroke Scale (NIHSS) score was the only significant predictor of ASPECTS decay, whereas other clinical characteristics, such as the use of IV thrombolysis and site of LVO, were similar between the two groups.ConclusionsIn our cohort, one out of three patients became ineligible for IA thrombectomy because of unfavorable ASPECTS ‘decay’ following inter-hospital transfer. Except for NIHSS severity, baseline clinical factors could not identify which patients were at risk for ASPECTS deterioration.
Preclinical Evaluation of Fatty Acid Synthase and EGFR Inhibition in Triple-Negative Breast Cancer
Authors: Giró-Perafita Ariadna , Palomeras Sònia , Lum David H. , Blancafort Adriana , Viñas Gemma , Oliveras Glòria , Pérez-Bueno Ferran , Sarrats Ariadna , Welm Alana L. , Puig Teresa 
Published: April 2016

Abstract
Purpose: Triple-negative breast cancer (TNBC) lacks an approved targeted therapy. Despite initial good response to chemotherapy, 30% of the patients relapse within 5 years after treatment. EGFR overexpression is a common marker in TNBC, and its expression has been correlated with poor outcome. Inhibition of fatty acid synthase (FASN) activity leads to apoptosis of human carcinoma cells overexpressing FASN. We tested the hypothesis that blocking FASN in combination with anti-EGFR signaling agents would be an effective antitumor strategy in sensitive and chemoresistant TNBC.
Experimental Design: Several TNBC cell lines and 29 primary tumors were included to determine whether FASN is a potential target in TNBC. Doxorubicin-resistant TNBC cell lines (231DXR and HCCDXR) have been developed and characterized in our laboratory. Cellular and molecular interactions of anti-FASN compounds (EGCG and C75) with cetuximab were analyzed. In vivo tumor growth inhibition was evaluated after cetuximab, EGCG, or the combination in TNBC orthoxenograft models.
Results: TNBC cell lines showed overexpression of FASN enzyme and its inhibition correlated to FASN levels. FASN staining was observed in all of the 29 TNBC tumor samples. In vitro, EGCG and C75 plus cetuximab showed strong synergism in sensitive and chemoresistant cells. In vivo, the combination of EGCG with cetuximab displayed strong antitumor activity against the sensitive and chemoresistant TNBC orthoxenografts, without signs of toxicity.
Conclusions: Our results show that the simultaneous blockade of FASN and EGFR is effective in preclinical models of sensitive and chemoresistant TNBC. Clin Cancer Res; 22(18); 4687–97. ©2016 AACR.
MSK1-Mediated β-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma
Authors: Wu Shaofang , Wang Shuzhen , Zheng Siyuan , Verhaak Roel , Koul Dimpy , Yung W.K. Alfred 
Published: April 2016

Abstract
Glioblastoma (GBM) represents a compelling disease for kinase inhibitor therapy because most of these tumors harbor genetic alterations that result in aberrant activation of growth factor–signaling pathways. The PI3K/mammalian target of the rapamycin (mTOR) pathway is dysregulated in over 50% of human GBM but remains a challenging clinical target. Inhibitors against PI3K/mTOR mediators have limited clinical efficacy as single agents. We investigated potential bypass mechanisms to PI3K/mTOR inhibition using gene expression profiling before and after PI3K inhibitor treatment by Affymetrix microarrays. Mitogen- and stress-activated protein kinase 1 (MSK1) was markedly induced after PI3K/mTOR inhibitor treatment and disruption of MSK1 by specific shRNAs attenuated resistance to PI3K/mTOR inhibitors in glioma-initiating cells (GIC). Further investigation showed that MSK1 phosphorylates β-catenin and regulates its nuclear translocation and transcriptional activity. The depletion of β-catenin potentiated PI3K/mTOR inhibitor-induced cytotoxicity and the inhibition of MSK1 synergized with PI3K/mTOR inhibitors to extend survival in an intracranial animal model and decreased phosphorylation of β-catenin at Ser552. These observations suggest that MSK1/β-catenin signaling serves as an escape survival signal upon PI3K/mTOR inhibition and provides a strong rationale for the combined use of PI3K/mTOR and MSK1/β-catenin inhibition to induce lethal growth inhibition in human GBM. Mol Cancer Ther; 15(7); 1656–68. ©2016 AACR.
Personalized Oncology Meets Immunology: The Path toward Precision Immunotherapy
Authors: Mandal Rajarsi , Chan Timothy A. 
Published: April 2016

AbstractPersonalized oncology aims to tailor therapy by targeting the unique genetic characteristics of a patient's tumor, whereas cancer immunotherapy focuses on activating the patient's immune system to control the tumor. The fusion of these ostensibly separate strategies has created a new dimension for personalized cancer immunotherapy. This entails the development of next-generation cancer vaccines that target neoantigens as well as the use of mutational signatures as predictive biomarkers for clinical response. The optimal use of immunotherapeutic agents will hinge on a robust understanding of the mutational profile of a cancer's genome that significantly dictates antitumor immunity and immunotherapeutic response.Significance: Cancer immunotherapy has provided substantial clinical benefit in a significant number of patients with advanced disease. However, the need for more precise immunotherapies and predictive biomarkers remains pressing. Recent progress in these areas has been promising and has created a framework for precision immune-oncology. Cancer Discov; 6(7); 703–13. ©2016 AACR.
Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis
Authors: Gillmore Julian D. , Maurer Mathew S. , Falk Rodney H. , Merlini Giampaolo , Damy Thibaud , Dispenzieri Angela , Wechalekar Ashutosh D. , Berk John L. , Quarta Candida C. , Grogan Martha , Lachmann Helen J. , Bokhari Sabahat , Castano Adam , Dorbala Sharmila , Johnson Geoff B. , Glaudemans Andor W.J.M. , Rezk Tamer , Fontana Marianna , Palladini Giovanni , Milani Paolo , Guidalotti Pierluigi L. , Flatman Katarina , Lane Thirusha , Vonberg Frederick W. , Whelan Carol J. , Moon James C. , Ruberg Frederick L. , Miller Edward J. , Hutt David F. , Hazenberg Bouke P. , Rapezzi Claudio , Hawkins Philip N. 
Published: April 2016

Background—
Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of echocardiography and the traditional requirement for histological confirmation. It has long been recognized that technetium-labeled bone scintigraphy tracers can localize to myocardial amyloid deposits, and use of this imaging modality for the diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicenter study to ascertain the diagnostic value of bone scintigraphy in this disease.

Methods and Results—
Results of bone scintigraphy and biochemical investigations were analyzed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Of 857 patients with histologically proven amyloid (374 with endomyocardial biopsies) and 360 patients subsequently confirmed to have nonamyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with false positives almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and the absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (positive predictive value confidence interval, 98.0–100).

Conclusions—
Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for histology in patients who do not have a monoclonal gammopathy. We propose noninvasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease.
Inhibition of D
4
Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells
Authors: Zhang Ye , Ren Hongmei , Lu Xi , He Duofen , Han Yu , Wang Hongyong , Zeng Chunyu , Shi Weibin 
Published: April 2016

Background

Ion transport in the renal proximal tubule (
RPT
), which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increases sodium reabsorption in
RPT
s, and hyperinsulinemic animals and patients have defective renal dopaminergic system. We presume that there is an inhibition of D
4
receptor on insulin receptor expression and effect, and the regulation is lost in spontaneously hypertensive rats (
SHR
s).

Methods and Results

Insulin receptor expression was determined by immunoblotting, and Na
+
‐K
+
‐
ATP
ase activity was detected in both Wistar‐Kyoto (
WKY
) and
SHR RPT
cells. Stimulation of D
4
receptor with
PD
168077 decreased expression of insulin receptors, which was blocked in the presence of the calcium‐channel blocker, nicardipine (10
−6
mol/L per 24 hours), in cell culture medium without calcium or in the presence of inositol 1,4,5‐trisphosphate (
IP
3) receptor blocker (2‐aminoethyl diphenylborinate [2‐
ADB]
; 10
−6
mol/L per 24 hours), indicating that extracellular calcium entry and calcium release from the endoplasmic reticulum were involved in the signal pathway. Stimulation of the insulin receptor stimulated Na
+
‐K
+
‐
ATP
ase activity, whereas pretreatment with
PD
168077 for 24 hours decreased the inhibitory effects of insulin receptor on Na
+
‐K
+
‐
ATP
ase activity in
WKY
cells. However, in
SHR
cells, inhibition of D
4
receptor on insulin receptor expression and effect were lost.

Conclusions

Activation of D
4
receptor inhibits insulin receptor expression in
RPT
cells from
WKY
rats. The aberrant inhibition of D
4
receptor on insulin receptor expression and effect might be involved in the pathogenesis of essential hypertension.
Costs and Benefits Associated With Transradial Versus Transfemoral Percutaneous Coronary Intervention in China
Authors: Jin Chen , Li Wei , Qiao Shu‐Bin , Yang Jin‐Gang , Wang Yang , He Pei‐Yuan , Tang Xin‐Ran , Dong Qiu‐Ting , Li Xiang‐Dong , Yan Hong‐Bing , Wu Yong‐Jian , Chen Ji‐Lin , Gao Run‐Lin , Yuan Jin‐Qing , Dou Ke‐Fei , Xu Bo , Zhao Wei , Zhang Xue , Xian Ying , Yang Yue‐Jin 
Published: April 2016

Background

Transradial percutaneous coronary intervention (
PCI
) has been increasingly adopted in clinical practice, given its potential advantages over transfemoral intervention; however, the impact of different access strategies on costs and clinical outcomes remains poorly defined, especially in the developing world.

Methods and Results

Using data from a consecutive cohort of 5306 patients undergoing
PCI
in China in 2010, we compared total hospital costs and in‐hospital outcomes for transradial intervention (
TRI)
and transfemoral intervention. Patients receiving
TRI
(n=4696, 88.5%) were slightly younger (mean age 57.4 versus 59.5 years), less often women (21.6% versus 33.1%), more likely to undergo
PCI
for single‐vessel disease, and less likely to undergo
PCI
for triple‐vessel or left main diseases. The unadjusted total hospital costs were 57 900 Chinese yuan (¥57 900; equivalent to 9190
US
dollars [$9190]) for
TRI
and ¥67 418 ($10,701) for transfemoral intervention. After adjusting for all observed patient and procedural characteristics using the propensity score inverse probability weighting method,
TRI
was associated with a lower total cost (adjusted difference ¥8081 [$1283]). More than 80% of the cost difference was related to lower
PCI
‐related costs (adjusted difference −¥5162 [−$819]), which were likely driven by exclusive use of vascular closure devices in transfemoral intervention, and lower hospitalization costs (−¥1399 [−$222]). Patients receiving
TRI
had shorter length of stay and were less likely to experience major adverse cardiac events or post‐
PCI
bleeding. These differences were consistent among clinically relevant subgroups with acute myocardial infarction, acute coronary syndrome, and stable angina.

Conclusions

Among patients undergoing
PCI
,
TRI
was associated with lower cost and favorable clinical outcomes compared with transfemoral intervention.
Endothelial Notch1 Is Required for Proper Development of the Semilunar Valves and Cardiac Outflow Tract
Authors: Koenig Sara N. , Bosse Kevin , Majumdar Uddalak , Bonachea Elizabeth M. , Radtke Freddy , Garg Vidu 
Published: April 2016

Background

Congenital heart disease is the most common type of birth defect, affecting ≈2% of the population. Malformations involving the cardiac outflow tract and semilunar valves account for >50% of these cases predominantly because of a bicuspid aortic valve, which has an estimated prevalence of 1% in the population. We previously reported that mutations in

NOTCH
1

were a cause of bicuspid aortic valve in nonsyndromic autosomal‐dominant human pedigrees. Subsequently, we described a highly penetrant mouse model of aortic valve disease, consisting of a bicuspid aortic valve with thickened cusps and associated stenosis and regurgitation, in
Notch1
‐haploinsufficient adult mice backcrossed into a
Nos3
‐null background.

Methods and Results

Here, we described the congenital cardiac abnormalities in
Notch1

+/−

;Nos3

−/−

embryos that led to ≈65% lethality by postnatal day 10. Although expected Mendelian ratios of
Notch1

+/−

;Nos3

−/−

embryos were found at embryonic day 18.5, histological examination revealed thickened, malformed semilunar valve leaflets accompanied by additional anomalies of the cardiac outflow tract including ventricular septal defects and overriding aorta. The aortic valve leaflets of
Notch1

+/−

;Nos3

−/−

embryos at embryonic day 15.5 were significantly thicker than controls, consistent with a defect in remodeling of the semilunar valve cushions. In addition, we generated mice haploinsufficient for
Notch1
specifically in endothelial and endothelial‐derived cells in a
Nos3
‐null background and found that
Notch1

fl
/+

;
Tie2‐Cre
+/−
;Nos3

−/−

mice recapitulate the congenital cardiac phenotype of
Notch1

+/−

;Nos3

−/−

embryos.

Conclusions
Our data demonstrate the role of endothelial Notch1 in the proper development of the semilunar valves and cardiac outflow tract.
Effect of a Simple Collagen Type I Sponge for Achilles Tendon Repair in a Rat Model
Authors: Müller Sebastian A. , Dürselen Lutz , Heisterbach Patricia , Evans Chris , Majewski Martin 
Published: April 2016

Background: Several sophisticated approaches to tendon engineering have been investigated as ways to improve tendon healing with the early formation of repair tissue with possibly a high amount of type I collagen. Besides the new formation of collagen type I, there is evidence for the natural integration of surrounding collagen type I from healthy tendon parts into the healing defect. However, the simple application of a type I collagen sponge to the healing site to increase the amount of local collagen type I has not been investigated. Hypothesis: Healing of the rat Achilles tendon can be accelerated by an additional supply of collagen type I, resulting in increased tear resistance. Study Design: Controlled laboratory study. Methods: The right Achilles tendons of 42 rats were transected. In half of the animals, a type I collagen sponge was placed into the gap. Animals were allowed to move freely in their cages to simulate early functional therapy. After 1, 2, and 4 weeks, tendon length, width, maximal load to failure, and stiffness were measured and the healing site studied histologically according to the Bonar score. Inflammation was evaluated by the appearance of macrophages and neutrophilic and eosinophilic granulocytes. Results: Defects receiving collagen sponges showed improved healing, with significantly stronger (29.5 vs 5.0 N, respectively, at 1 week; P = .00003), shorter (11.6 vs 14.5 mm, respectively, at 4 weeks; P = .005), thicker (10.0 vs 1.8 mm2, respectively, at 1 week; P = .00002), and less stiff (19.5 vs 30.5 N/mm, respectively, at 4 weeks; P = .02) tendons than control tendons. Overall, the biomechanical properties of the collagen-treated tendons appeared to be significantly closer to those of native, uninjured tendons compared with tendons in the control group. Histologically, no inflammatory reaction due to the collagen sponge was found. Conclusion: Tendon healing was accelerated by the type I collagen sponge. Moreover, the mechanical properties of collagen-treated tendons appeared to be significantly closer to those of normal, uninjured tendons compared with control tendons without collagen treatment. Clinical Relevance: As a simple type I collagen sponge seems to increase the amount of local collagen type I, the careful use of such sponges might be an option for tendon augmentation during Achilles tendon surgery.
Ask the eConsultant: Improving access to haematology expertise using an asynchronous eConsult system
Authors: Fogel Adam , Khamisa Karima , Afkham Amir , Liddy Clare , Keely Erin 
Published: April 2016

Introduction The Champlain BASE (Building Access to Specialists through eConsultation) eConsultation service was designed to address the limited access to specialist care in Canada, which can lead to long waiting times and, subsequently, negative patient outcomes. Our primary objective was to perform an in-depth analysis of the use, content, and perceived value of haematology electronic consults (eConsults) submitted by primary care providers (PCPs) to the eConsult service. Methods We conducted a cross-sectional study using descriptive statistics to examine post-eConsult surveys for PCPs and other collected data including PCP designation, time for specialist to complete the eConsult, specialist response time, perceived value of the eConsult by the PCP, and the need for a face-to-face referral following the eConsult. A medically-trained author reviewed all haematology eConsults from April 2011 to January 2015, and categorized them by clinical topic and question type using validated taxonomies. Results Haematology accounted for 436 out of 5601 (7.8%) total eConsults, making it the third most popular service utilized. In 66% of haematology eConsults, a face-to-face consultation was not needed. Anaemia, neutropenia, and hyperferritinemia were the most common clinical queries. Most eConsult question types concerned the management of haematological disorders or the interpretation of laboratory tests. Most eConsults were answered within three days, using less than 15 minutes of the specialists’ time. PCPs highly valued the service. Discussion This initiative increases access to haematology care and has the potential to reduce the long waiting times for non-urgent traditional consultation, along with the benefit of cost savings to the healthcare system.
Patient outcome after surgical management of the spinal accessory nerve injury: A long-term follow-up study
Authors: Göransson Harry , Leppänen Olli V , Vastamäki Martti 
Published: April 2016

Objectives: A lesion in the spinal accessory nerve is typically iatrogenic: related to lymph node biopsy or excision. This injury may cause paralysis of the trapezius muscle and thus result in a characteristic group of symptoms and signs, including depression and winging of the scapula, drooped shoulder, reduced shoulder abduction, and pain. The elements evaluated in this long-term follow-up study include range of shoulder motion, pain, patients’ satisfaction, delay of surgery, surgical procedure, occupational status, functional outcome, and other clinical findings. Methods: We reviewed the medical records of a consecutive 37 patients (11 men and 26 women) having surgery to correct spinal accessory nerve injury. Neurolysis was the procedure in 24 cases, direct nerve repair for 9 patients, and nerve grafting for 4. Time elapsed between the injury and the surgical operation ranged from 2 to 120 months. The patients were interviewed and clinically examined after an average of 10.2 years postoperatively. Results: The mean active range of movement of the shoulder improved at abduction 44° (43%) in neurolysis, 59° (71%) in direct nerve repair, and 30° (22%) in nerve-grafting patients. No or only slight atrophy of the trapezius muscle was observable in 75%, 44%, and 50%, and no or controllable pain was observable in 63%, 56%, and 50%. Restriction of shoulder abduction preceded deterioration of shoulder flexion. Patients’ overall dissatisfaction with the state of their upper extremity was associated with pain, lower strength in shoulder movements, and occupational problems. Conclusion: We recommend avoiding unnecessary delay in the exploration of the spinal accessory nerve, if a neural lesion is suspected.