bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trial protocol to compare the efficacy of a smartphone-based blood glucose management system with standard clinic care in the gestational diabetic population
Authors: Mackillop Lucy H , Bartlett Katy , Birks Jacqueline , Farmer Andrew J , Gibson Oliver J , Kevat Dev A , Kenworthy Yvonne , Levy Jonathan C , Loerup Lise , Tarassenko Lionel , Velardo Carmelo , Hirst Jane E 
Published: March 2016

IntroductionThe prevalence of gestational diabetes mellitus (GDM) is rising in the UK. Good glycaemic control improves maternal and neonatal outcomes. Frequent clinical review of patients with GDM by healthcare professionals is required owing to the rapidly changing physiology of pregnancy and its unpredictable course. Novel technologies that allow home blood glucose (BG) monitoring with results transmitted in real time to a healthcare professional have the potential to deliver good-quality healthcare to women more conveniently and at a lower cost to the patient and the healthcare provider compared to the conventional face-to-face or telephone-based consultation. We have developed an integrated GDm-health management system and aim to test the impact of using this system on maternal glycaemic control, costs, patient satisfaction and maternal and neonatal outcomes compared to standard clinic care in a single large publicly funded (National Health Service (NHS)) maternity unit.Methods and analysisWomen with confirmed gestational diabetes in a current pregnancy are individually randomised to either the GDm-health system and half the normal clinic visits or normal clinic care. Primary outcome is mean BG in each group from recruitment to delivery calculated, with adjustments made for number of BG measurements, proportion of preprandial and postprandial readings and length of time in study, and compared between the groups. The secondary objective will be to compare the two groups for compliance to the allocated BG monitoring regime, maternal and neonatal outcomes, glycaemic control using glycated haemoglobin (HbA1c) and other BG metrics, and patient attitudes to care assessed using a questionnaire and resource use.Ethics and disseminationThresholds for treatment, dietary advice and clinical management are the same in both groups. The results of the study will be published in a peer-reviewed journal and disseminated electronically and in print.Trial registration numberNCT01916694; Pre-results.
Predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis
Authors: Cheung Peter P , Mari Karine , Devauchelle-Pensec Valérie , Jousse-Joulin Sandrine , D'Agostino Maria Antonietta , Chalès Gérard , Gaudin Philippe , Mariette Xavier , Saraux Alain , Dougados Maxime 
Published: March 2016

ObjectiveTo evaluate the predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis (RA).MethodsA post hoc analysis was performed on a prospective 2-year study of 59 patients with active RA starting on antitumour necrosis factor (TNF). Tenderness and synovitis was assessed clinically at baseline, followed by blinded ultrasound assessment (B-mode and power Doppler ultrasound (PDUS)) on the hands and feet (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal and 10 metatarsophalangeal (MTP) joints). Radiographs of these joints were performed at baseline and at 2 years. The risk of radiographic progression with respect to the presence of baseline tenderness or synovitis, as well as its persistence (after 4 months of anti-TNF), was estimated by OR (95% CI).ResultsBaseline tender joints were the least predictive for radiographic progression (OR=1.53 (95% CI 1.02 to 2.29) p<0.04), when compared to synovitis (clinical OR=2.08 (95% CI 1.39 to 3.11) p<0.001 or PDUS OR=1.80 (95% CI 1.20 to 2.71) p=0.005, respectively). Tender joints with the presence of synovitis were predictive of radiographic progression (OR=1.89 (95% CI 1.25 to 2.85) p=0.002), especially seen in the MTP joints. Non-tender joints with no synovitis were negatively predictive (OR=0.57 (95% CI 0.39 to 0.82) p=0.003). Persistence of tender joints was negatively predictive (OR=0.38 (95% CI 0.18 to 0.78) p=0.009) while persistence of synovitis was predictive (OR=2.41 (95% CI 1.24 to 4.67) p=0.01) of radiographic progression.ConclusionsSynovitis is better than tenderness to predict for subsequent structural progression. However, coexistence of tenderness and synovitis at the level of an individual joint is predictive of structural damage, particularly in the MTP joints.Trial registration numberNCT00444691.
BEVA
Authors: Zhou Xiaoling , Qin Jianbin , Xiao Chuan , Wang Wei , Lin Xuemin , Ishikawa Yoshiharu 
Published: March 2016

Query autocompletion has become a standard feature in many search applications, especially for search engines. A recent trend is to support theerror-tolerant autocompletion, which increases the usability significantly by matching prefixes of database strings and allowing a small number of errors.In this article, we systematically study the query processing problem for error-tolerant autocompletion with a given edit distance threshold. We propose a general framework that encompasses existing methods and characterizes different classes of algorithms and the minimum amount of information they need to maintain under different constraints. We then propose a novel evaluation strategy that achieves the minimum active node size by eliminating ancestor-descendant relationships among active nodes entirely. In addition, we characterize the essence of edit distance computation by a novel data structure namededit vector automaton(EVA). It enables us to compute new active nodes and their associated states efficiently by table lookups. In order to support large distance thresholds, we devise a partitioning scheme to reduce the size and construction cost of the automaton, which results in theuniversal partitioned EVA(UPEVA) to handle arbitrarily large thresholds. Our extensive evaluation demonstrates that our proposed method outperforms existing approaches in both space and time efficiencies.
On Choosing Server- or Client-Side Solutions for BFT
Authors: Platania Marco , Obenshain Daniel , Tantillo Thomas , Amir Yair , Suri Neeraj 
Published: March 2016

Byzantine Fault Tolerant (BFT) protocols have the ability to work correctly even when up to a threshold
f
of system servers are compromised. This makes them appealing for the construction of critical systems connected to the Internet, which are constantly a target for cyber attacks.

BFT protocols differ based on the kind of application, deployment settings, performance, access control mechanisms, number of servers in the system, and protocol implementation. The large number of protocols present in the literature and their differences make it difficult for a system builder to choose the solution that best satisfies the requirements of the system that he wants to build. In particular, the main difference among BFT protocols lies in their system models: server-side versus client-side. In the server-side model each client relies on the system to consistently order and replicate updates, while in the client-side model each client actively participates in the protocol.
In this article, we classify BFT protocols as server-side or client-side. We analyze the trade-offs between the two models, describe systems that use these models and the trade-offs they choose, highlight the research gaps, and provide guidelines to system builders in order to choose the solution that best satisfies their needs.
ΔNp63α Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGFβ-Induced Metastasis
Authors: Rodriguez Calleja Lidia , Jacques Camille , Lamoureux François , Baud'huin Marc , Tellez Gabriel Marta , Quillard Thibaut , Sahay Debashish , Perrot Pierre , Amiaud Jerome , Charrier Celine , Brion Regis , Lecanda Fernando , Verrecchia Franck , Heymann Dominique , Ellisen Leif W. , Ory Benjamin 
Published: March 2016

Abstract
Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an antimetastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, ΔNp63α, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which ΔNp63α-expressing cells within a TGFβ-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of ΔNp63α-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that ΔNp63α repressed miR-527 and miR-665, leading to the upregulation of two TGFβ effectors, SMAD4 and TβRII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for ΔNp63α in the normal wound-healing response. We show that ΔNp63α-mediated repression of miR-527/665 controls a TGFβ-dependent signaling node that switches off antimigratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel miRNA network involved in the regulation of physiologic wound-healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination. Cancer Res; 76(11); 3236–51. ©2016 AACR.
Precision Medicine for Diffuse Large B-cell Lymphoma
Authors: Lim Megan S. , Elenitoba-Johnson Kojo S.J. 
Published: March 2016

Abstract
This study demonstrates the clinical utility of a targeted gene sequencing panel “the Lymphopanel,” which enables the detection of actionable mutations and subtype-enriched gene alterations in diffuse large B-cell lymphoma that will pave the way to precision therapy era for patients with this form of aggressive lymphoma. Clin Cancer Res; 22(12); 2829–31. ©2016 AACR.
See related article by Dubois et al., p. 2919
Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies
Authors: Cornet Sébastien , Mathé Doriane , Chettab Kamel , Evesque Anne , Matera Eva-Laure , Trédan Olivier , Dumontet Charles 
Published: March 2016

AbstractTherapeutic mAbs exert antitumor activity through various mechanisms, including apoptotic signalization, complement-dependent cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP). G-CSF and GM-CSF have been reported to increase the activity of antibodies in preclinical models and in clinical trials. To determine the potential role of pegfilgrastim as an enhancer of anticancer antibodies, we performed a comparative study of filgrastim and pegfilgrastim. We found that pegfilgrastim was significantly more potent than filgrastim in murine xenograft models treated with mAbs. This was observed with rituximab in CD20+ models and with trastuzumab in HER2+ models. Stimulation with pegfilgrastim was associated with significant enhancement of leukocyte content in spleen as well as mobilization of activated monocytes/granulocytes from the spleen to the tumor bed. These results suggest that pegfilgrastim could constitute a potent adjuvant for immunotherapy with mAbs possessing ADCC/ADCP properties. Mol Cancer Ther; 15(6); 1238–47. ©2016 AACR.
Signaling of Serum Amyloid A Through Receptor for Advanced Glycation End Products as a Possible Mechanism for Uremia-Related Atherosclerosis
Authors: Belmokhtar Karim , Robert Thomas , Ortillon Jeremy , Braconnier Antoine , Vuiblet Vincent , Boulagnon-Rombi Camille , Diebold Marie Danièle , Pietrement Christine , Schmidt Ann Marie , Rieu Philippe , Touré Fatouma 
Published: March 2016

Objective—
Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. Serum amyloid A (SAA) is an acute phase protein and a binding partner for the multiligand receptor for advanced glycation end products (RAGE). We investigated the role of the interaction between SAA and RAGE in uremia-related atherogenesis.

Approach and Results—

We used a mouse model of uremic vasculopathy, induced by 5 of 6 nephrectomy in the
Apoe
−/−
background. Sham-operated mice were used as controls. Primary cultures of
Ager
+/+
and
Ager
−/−
vascular smooth muscle cells (VSMCs) were stimulated with recombinant SAA, S100B, or vehicle alone. Relevance to human disease was assessed with human VSMCs. The surface area of atherosclerotic lesions at the aortic roots was larger in uremic
Apoe
−/−
than in sham-operated
Apoe
−/−
mice (
P
<0.001). Furthermore, atherosclerotic lesions displayed intense immunostaining for RAGE and SAA, with a pattern similar to that of α-SMA.
Ager
transcript levels in the aorta were 6× higher in uremic animals than in controls (
P
<0.0001). Serum SAA concentrations were higher in uremic mice, not only after 4 weeks of uremia but also at 8 and 12 weeks of uremia, than in sham-operated animals. We investigated the functional role of RAGE in uremia-induced atherosclerosis further, in animals lacking RAGE. We found that the induction of uremia in
Apoe
−/−
Ager
−/−
mice did not accelerate atherosclerosis. In vitro, the stimulation of
Ager
+/+
but not of
Ager
−/−
VSMCs with SAA or S100B significantly induced the production of reactive oxygen species, the phosphorylation of AKT and mitogen-activated protein kinase-extracellular signal-regulated kinases and cell migration. Reactive oxygen species inhibition with N-acetyl cysteine significantly inhibited both the phosphorylation of AKT and the migration of VSMCs. Similar results were obtained for human VSMCs, except that the phosphorylation of mitogen-activated protein kinase-extracellular signal-regulated kinases, rather than of AKT, was subject to specific redox-regulation by SAA and S100B. Furthermore, human aortic atherosclerotic sections were positively stained for RAGE and SAA.

Conclusions—

Uremia upregulates SAA and RAGE expression in the aortic wall and in atherosclerotic lesions in mice. Ager
−/−
animals are protected against the uremia-induced acceleration of atherosclerosis. SAA modulates the functions of murine and human VSMCs in vitro in a RAGE-dependent manner. This study, therefore, identifies SAA as a potential new uremic toxin involved in uremia-related atherosclerosis through interaction with RAGE.
Pharmacologically Improved Contractility Protects Against Aortic Dissection in Mice With Disrupted Transforming Growth Factor-β Signaling Despite Compromised Extracellular Matrix Properties
Authors: Ferruzzi Jacopo , Murtada Sae-Il , Li Guangxin , Jiao Yang , Uman Selen , Ting Magdalene Y.L. , Tellides George , Humphrey Jay D. 
Published: March 2016

Objective—
Transforming growth factor-beta is a pleiotropic cytokine having diverse roles in vascular morphogenesis, homeostasis, and pathogenesis. Altered activity of and signaling through transforming growth factor-beta has been implicated in thoracic aortic aneurysms and dissections, conditions characterized by a reduced structural integrity of the wall that associates with altered biomechanics and mechanobiology. We quantify and contrast the passive and active biaxial biomechanical properties of the ascending and proximal descending thoracic aorta in a mouse model of altered transforming growth factor-beta signaling, with and without treatment with rapamycin.

Approach and Results—

Postnatal disruption of the gene (
Tgfbr2
) that codes the type II transforming growth factor-beta receptor compromises vessel-level contractility and elasticity. Daily treatment with rapamycin, a mechanistic target of rapamycin inhibitor that protects against aortic dissection in these mice, largely preserves or restores the contractile function while the passive properties remain compromised. Importantly, this increased smooth muscle contractility protects an otherwise vulnerable aortic wall from pressure-induced intramural delaminations in vitro.

Conclusions—
Notwithstanding the protection afforded by rapamycin in vivo and in vitro, the residual mechanical dysfunctionality suggests a need for caution if rapamycin is to be considered as a potential therapeutic. There is a need for in vivo evaluations in cases of increased hemodynamic loading, including hypertension or extreme exercise, which could unduly stress a structurally vulnerable aortic wall. Given these promising early results, however, such studies are clearly warranted.
Hemobilia following laparoscopic cholecystectomy: computed tomography findings and clinical outcome of transcatheter arterial embolization
Authors: Feng Wen , Yue Dong , ZaiMing Lu , ZhaoYu Liu , Wei Li , Qiyong Guo 
Published: March 2016

Background Hemobilia following laparoscopic cholecystectomy (LC) can occur in the early or late postoperative course and poses a diagnostic and therapeutic challenge. Purpose To assess computed tomography (CT) findings and clinical outcomes after transcatheter arterial embolization (TAE) in patients presenting with hemobilia following LC. Material and Methods Fourteen patients treated for hemobilia following LC were included in the study. Three patients were diagnosed by endoscopy and 11 by abdominal contrast-enhanced CT. Coils or microcoils were superselectively deployed to occlude the bleeding vessel during TAE. Abdominal CT findings of hemobilia, and the success rate and complication of TAE were observed. Results Abdominal CT provided the following signs of hemobilia: hematoma within the abdominal cavity and gallbladder fossa, blood clots containing high attenuation within the bile duct, biliary dilatation, pseudoaneurysm of the right hepatic artery, contrast extravasation, enhancement of the bile duct wall, and hypoperfusion of the right lobe. The success rate of TAE was 100% and rebleeding did not occur in any patient. Post-embolization syndrome and hepatic ischemia occurred in nine patients, which was associated with age and the time interval between the LC and TAE. Conclusion Abdominal CT provided direct signs that can aid in the diagnosis of hemobilia after LC. TAE allowed for successful treatment of hemobilia with minor complications.
Intravesical botulinum toxin-A: Does the injection template matter?
Authors: Broome JD , Irwin PP 
Published: March 2016

Objective: The efficacy of intravesical botulinum toxin-A (BTX-A) for the treatment of idiopathic detrusor overactivity (IDO) is well-established and evidence-based. The optimal regime in terms of dose, distribution, depth of injection and number of injections has not been determined and there is still considerable variation throughout clinical practice. We aim to establish the optimum template for bladder injections. Patients and methods: All patients had urodynamically-proven IDO which had failed conservative and medical management. AbobotulinumtoxinA (250 units) was injected into the detrusor and sub-urothelium in one of five injection templates under general anaesthetic. An Overactive Bladder Symptom Score (OABSS) and International Prostate Symptoms Score (IPSS)-Likert quality of life (QoL) score was completed pre-operatively and at six weeks post-operatively. In those who underwent repeat treatments the time to re-commencement of pharmacological therapy was recorded. Results: In total 111 patients received 170 treatments. The average age of patients was 57 (range: 17–86) and the male: female ratio was 0.18:1. Overall there was a mean improvement in the OABSS by −3.7 points±4.29 (standard deviation (SD) ( p<0.01) and an average change in the QoL score of −2.18±2.17 (SD) ( p<0.01) with BTX-A treatment. When analysed by template subgroup there was no statistically significant difference in the magnitude of change for any template over the other four for either the OABSS ( p=0.78) or QoL scores ( p=0.56). Forty-one patients had multiple treatments and had data collected for the duration to treatment failure. The overall average time to treatment failure was 11.2±7.9 months. Subgroup analysis showed that there was no statistically significant ( p=0.783) difference in time to treatment failure for any one of the injection distributions. Conclusion: This study has shown that altering the injection protocol of BTX-A did not affect the clinical outcome in terms of symptoms, QoL or in the time to treatment failure.
Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia in a cat
Authors: Linton Michael , Tong Lydia , Simon Adrian , Buffa Eugene , McGregor Ross , Labruyére Julien , Foster Darren 
Published: March 2016

Case summary A 14-year-old, female neutered domestic shorthair presented for dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous mass was present within the pericardial sac, and the mass continued caudally with the mesenteric fat. On CT, the outline of the diaphragm was not continuous and there was an obvious defect with diaphragmatic thickening present at the mid-level of the liver. A pleural effusion and a small-volume pericardial effusion were also present. A ventral midline coeliotomy and median sternotomy revealed a 5 × 6 × 7 cm firm, irregular, tan-coloured soft tissue mass within the pericardial sac attached to both the diaphragmatic defect and liver. The mass was carefully dissected away from the heart and the diaphragmatic defect was repaired with primary closure. Postoperatively, the cat had a persistent pneumothorax that required continuous pleural suction for 41 h. The cat died 44 h postoperatively. Histopathology and immunohistochemistry confirmed the mass to be a hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH). Relevance and novel information This is the first reported case of metaplastic transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic fibrosarcoma is a rarely reported location for fibrosarcoma in this species.
The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma
Authors: Kuruvilla John 
Published: March 2016

AbstractDespite improvements over the past decade in the overall survival of patients with indolent non-Hodgkin lymphomas, these lymphomas remain largely incurable with standard therapies. Immunochemotherapy with rituximab-based regimens has become a well-established standard of care in the primary and relapsed disease settings. The role of hematopoietic stem cell transplantation in indolent lymphoma has been defined by the adoption of this therapy largely in the relapse setting because randomized trials in the first-line setting have not shown survival advantages. Allogeneic stem cell transplantation has the possibility for cure because of the potential for immunologic graft-versus-lymphoma effect, but there are significant concerns regarding nonrelapse mortality. Autologous stem cell transplantation offers a safe treatment platform, but relapse remains a significant issue. The role of transplantation in the current treatment landscape of immunochemotherapy has not been conclusively proven, and randomized trials are lacking. This review summarizes the current relevant data regarding transplantation in indolent non-Hodgkin lymphoma and highlights the issues relevant to clinicians in the field.