bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858)
Authors: Unciuleac Mihaela-Carmen , Smith Paul C. , Shuman Stewart 
Published: March 2016

ABSTRACT

AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a
Mycobacterium smegmatis
AAA protein Msm0858, the ortholog of
Mycobacterium tuberculosis
Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer.

IMPORTANCE
Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a structural homolog of mammalian p97, with respect to the linear order and tertiary structures of their domains.
Acupuncture for Patients with Lumbar Spinal Stenosis: A Randomised Pilot Trial
Authors: Kim Kun Hyung , Kim Yu Ri , Baik Seung Kug , Noh Seung Hee , Kim Dae Hun , Lee Sang Weon , Yang Gi Young 
Published: March 2016

Objective To assess the safety and feasibility of acupuncture for participants with symptomatic lumbar spinal stenosis (LSS) in a pilot study. Methods 50 participants with a clinical and radiological diagnosis of LSS were randomised to receive acupuncture combined with usual care (acupuncture group), or usual care alone (control group). Participants in the acupuncture group were offered 12–16 sessions of manual acupuncture±electroacupuncture over 6 weeks and maintained their usual self-management. The control group was provided with physical therapy as required and maintained their usual self-management. The primary outcome was the change in back-specific functional status, as measured by the Oswestry disability index (ODI) at the 3-month follow-up. Secondary outcomes included symptoms and other relevant domains. Outcome assessors were not blinded. Results 39 participants (78%) completed the trial with 524 treatment visits. There were no significant differences between the two groups in back-specific function (ODI: mean difference −2.5, 95% CI −8.9 to 3.8). Pain in the back and/or leg showed small improvements at 3 months, while there were no significant differences in other secondary outcomes. The total number of adverse events was 61 (12% of 524 treatment visits). All but one were minor and transient. The one severe adverse event was deemed to be unrelated to acupuncture. Conclusions The study was feasible. Acupuncture combined with usual care did not confer significant functional improvements over usual care alone. Further randomised trials with adequate sample sizes and outcome assessor blinding are warranted to evaluate the role of acupuncture for LSS. Trial Registration Number NCT01987622.
Is it taking longer to die in paediatric intensive care in England and Wales?
Authors: Plunkett Adrian , Parslow Roger C 
Published: March 2016

IntroductionAll-cause infant and childhood mortality has decreased in the UK over the last 30 years. Advances in paediatric critical care have increased survival in paediatric intensive care units (PICUs) but may have affected how and when children die in PICU. We explored factors affecting length of stay (LOS) of children who died in PICU over an 11-year period.MethodsWe analysed demographic and clinical data of 165 473 admissions to PICUs in England and Wales, from January 2003 to December 2013. We assessed time trends in LOS for survivors and non-survivors and explored the effect of demographic and clinical characteristics on LOS for non-survivors.ResultsLOS increased 0.310 days per year in non-survivors (95% CI 0.169 to 0.449) and 0.064 days per year in survivors (95% CI 0.046 to 0.083). The proportion of early deaths (<24 h of admission) fell 0.44% points per year (95% CI −0.971 to 0.094), but the proportion of late deaths (>28 days of PICU stay) increased by 0.44% points per year (95% CI 0.185 to 0.691). The paediatric index of mortality score in early deaths increased by 0.77% points per year (95% CI 0.31% to 1.23%).DiscussionIncreased LOS in children who die in PICU is driven by a decreased proportion of early deaths and an increased proportion of late deaths. This trend, combined with an increase in the severity of illness in early deaths, is consistent with a reduction in early mortality for acutely ill children, but a prolongation of life for those children admitted to PICU with life-limiting illnesses.
Gender-informed, psychoeducational programme for couples to prevent postnatal common mental disorders among primiparous women: cluster randomised controlled trial
Authors: Fisher Jane , Rowe Heather , Wynter Karen , Tran Thach , Lorgelly Paula , Amir Lisa H , Proimos Jenny , Ranasinha Sanjeeva , Hiscock Harriet , Bayer Jordana , Cann Warren 
Published: March 2016

ObjectivesInterventions to prevent postpartum common mental disorders (PCMD) among unselected populations of women have had limited success. The aim was to determine whether What Were We Thinking (WWWT) a gender-informed, psychoeducational programme for couples and babies can prevent PCMD among primiparous women 6 months postpartum.DesignCluster-randomised controlled trial.Setting48 Maternal and Child Health Centres (MCHCs) from 6 Local Government Areas in Melbourne, Australia were allocated randomly to usual care (24) or usual care plus WWWT (24).ParticipantsEnglish-speaking primiparous women receiving primary care at trial MCHCs were recruited to the intervention (204) and control (196) conditions. Of these, 187 (91.7%) and 177 (90.3%) provided complete data.InterventionWWWT is a manualised programme comprising primary care from a trained nurse, print materials and a face-to-face seminar.Main outcome measuresData sources were standardised and study-specific measures collected in blinded computer-assisted telephone interviews at 6 and 26 weeks postpartum. The primary outcome was PCMD assessed by Composite International Diagnostic Interviews and Patient Health Questionnaire (PHQ) Depression and Generalised Anxiety Disorder modules.ResultsIn intention-to-treat analyses the adjusted OR (AOR) of PCMD in the intervention compared to the usual care group was 0.78 (95% CI 0.38 to 1.63, ns), but mild to moderate anxiety symptoms (AOR 0.58, 95% CI 0.35 to 0.97) and poor self-rated health (AOR 0.46, 95% CI 0.22 to 0.97) were significantly lower. In a per protocol analysis, comparing the full (three component) intervention and usual care groups, the AOR of PCMD was 0.36, (95% CI 0.14 to 0.95). The WWWT seminar was appraised as salient, comprehensible and useful by >85% participants. No harms were detected.ConclusionsWWWT is readily integrated into primary care, enables inclusion of fathers and addresses modifiable risks for PCMD directly. The full intervention appears a promising programme for preventing PCMD, optimising family functioning, and as the first component of a stepped approach to mental healthcare.Trial registration numberACTRN12613000506796; Results.
Do patients' disruptive behaviours influence the accuracy of a doctor's diagnosis? A randomised experiment
Authors: Schmidt H G , van Gog Tamara , CE Schuit Stephanie , Van den Berge Kees , LA Van Daele Paul , Bueving Herman , Van der Zee Tim , W Van den Broek Walter , LCM Van Saase Jan , Mamede Sílvia 
Published: March 2016

BackgroundLiterature suggests that patients who display disruptive behaviours in the consulting room fuel negative emotions in doctors. These emotions, in turn, are said to cause diagnostic errors. Evidence substantiating this claim is however lacking. The purpose of the present experiment was to study the effect of such difficult patients’ behaviours on doctors’ diagnostic performance.MethodsWe created six vignettes in which patients were depicted as difficult (displaying distressing behaviours) or neutral. Three clinical cases were deemed to be diagnostically simple and three deemed diagnostically complex. Sixty-three family practice residents were asked to evaluate the vignettes and make the patient's diagnosis quickly and then through deliberate reflection. In addition, amount of time needed to arrive at a diagnosis was measured. Finally, the participants rated the patient's likability.ResultsMean diagnostic accuracy scores (range 0–1) were significantly lower for difficult than for neutral patients (0.54 vs 0.64; p=0.017). Overall diagnostic accuracy was higher for simple than for complex cases. Deliberate reflection upon the case improved initial diagnostic, regardless of case complexity and of patient behaviours (0.60 vs 0.68, p=0.002). Amount of time needed to diagnose the case was similar regardless of the patient's behaviour. Finally, average likability ratings were lower for difficult than for neutral-patient cases.ConclusionsDisruptive behaviours displayed by patients seem to induce doctors to make diagnostic errors. Interestingly, the confrontation with difficult patients does however not cause the doctor to spend less time on such case. Time can therefore not be considered an intermediary between the way the patient is perceived, his or her likability and diagnostic performance.
Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia
Authors: Senda Miho , Fukuyama Ryuichi , Nagasaka Tetsuro 
Published: March 2016

AimsTo determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis.MethodsWe enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group.ResultsWe determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients.ConclusionsThese results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT.
Stent-assisted coiling versus coiling alone of poor-grade ruptured intracranial aneurysms: a multicenter study
Authors: Zhao Bing , Tan Xianxi , Yang Hua , Zheng Kuang , Li Zequn , Xiong Ye , Zhong Ming 
Published: March 2016

IntroductionEndovascular coiling is a valid treatment option for poor-grade ruptured aneurysms. However, little is known about stent-assisted coiling of poor-grade aneurysms.ObjectiveTo compare the safety and efficacy of stent-assisted coiling with coiling alone for poor-grade aneurysms.MethodsUsing multicenter data on poor-grade aneurysms, we performed a retrospective analysis of 131 consecutive patients treated with endovascular coiling within 14 days after ictus. Patients were split into two groups: stent-assisted coiling and coiling alone. Baseline characteristics, immediate angiographic results, perioperative complications, and clinical outcomes were compared between the two groups.ResultsTwenty-three (17.6%) patients were treated with stent-assisted coiling and 108 (82.4%) with coiling alone. There were no statistically significant differences in patient age, sex, clinical grade, Fisher grade, modified Fisher grade, aneurysm location, and size between the stent-assisted coiling and coiling alone groups. Intraprocedural aneurysm rupture, procedure-related ischemic complication, external ventricular drainage-related hemorrhagic complication, and symptomatic vasospasm did not differ between the two groups. Immediate angiographic results and clinical outcomes at discharge and at 6 and 12 months did not differ between the groups. Aneurysm rebleeding occurred in 4 (17.4%) patients after stent-assisted coiling compared with 2 (1.9%) patients after coiling alone (p<0.007). Multivariate analysis showed that incomplete aneurysm occlusion was independently associated with aneurysm rebleeding (p=0.016), and there was a trend toward aneurysm rebleeding after stent-assisted coiling (p=0.051).ConclusionsStent-assisted coiling of poor-grade aneurysms is feasible and safe compared with coiling alone. However, the hemorrhagic complication and aneurysm rebleeding may not be negligible.
Trial protocol for a randomised controlled trial of red cell washing for the attenuation of transfusion-associated organ injury in cardiac surgery: the REDWASH trial
Authors: Murphy G J , Verheyden V , Wozniak M , Sullo N , Dott W , Bhudia S , Bittar N , Morris T , Ring A , Tebbatt A , Kumar T 
Published: March 2016

IntroductionIt has been suggested that removal of proinflammatory substances that accumulate in stored donor red cells by mechanical cell washing may attenuate inflammation and organ injury in transfused cardiac surgery patients. This trial will test the hypotheses that the severity of the postoperative inflammatory response will be less and postoperative recovery faster if patients undergoing cardiac surgery receive washed red cells compared with standard care (unwashed red cells).Methods and analysisAdult (≥16 years) cardiac surgery patients identified at being at increased risk for receiving large volume red cell transfusions at 1 of 3 UK cardiac centres will be randomly allocated in a 1:1 ratio to either red cell washing or standard care. The primary outcome is serum interleukin-8 measured at 5 postsurgery time points up to 96 h. Secondary outcomes will include measures of inflammation, organ injury and volumes of blood transfused and cost-effectiveness. Allocation concealment, internet-based randomisation stratified by operation type and recruiting centre, and blinding of outcome assessors will reduce the risk of bias. The trial will test the superiority of red cell washing versus standard care. A sample size of 170 patients was chosen in order to detect a small-to-moderate target difference, with 80% power and 5% significance (2-tailed).Ethics and disseminationThe trial protocol was approved by a UK ethics committee (reference 12/EM/0475). The trial findings will be disseminated in scientific journals and meetings.Trial registration numberISRCTN 27076315.
Parallelizing the Chambolle Algorithm for Performance-Optimized Mapping on FPGA Devices
Authors: Beretta Ivan , Rana Vincenzo , Akin Abdulkadir , Nacci Alessandro Antonio , Sciuto Donatella , Atienza David 
Published: March 2016

The performance and the efficiency of recent computing platforms have been deeply influenced by the widespread adoption of hardware accelerators, such as graphics processing units (GPUs) or field-programmable gate arrays (FPGAs), which are often employed to support the tasks of general-purpose processors (GPPs). One of the main advantages of these accelerators over their sequential counterparts (GPPs) is their ability to perform massive parallel computation. However, to exploit this competitive edge, it is necessary to extract the parallelism from the target algorithm to be executed, which generally is a very challenging task.
This concept is demonstrated, for instance, by the poor performance achieved on relevant multimedia algorithms, such as Chambolle, which is a well-known algorithm employed for the optical flow estimation. The implementations of this algorithm that can be found in the state of the art are generally based on GPUs but barely improve the performance that can be obtained with a powerful GPP. In this article, we propose a novel approach to extract the parallelism from computation-intensive multimedia algorithms, which includes an analysis of their dependency schema and an assessment of their data reuse. We then perform a thorough analysis of the Chambolle algorithm, providing a formal proof of its inner data dependencies and locality properties. Then, we exploit the considerations drawn from this analysis by proposing an architectural template that takes advantage of the fine-grained parallelism of FPGA devices. Moreover, since the proposed template can be instantiated with different parameters, we also propose a design metric, the expansion rate, to help the designer in the estimation of the efficiency and performance of the different instances, making it possible to select the right one before the implementation phase. We finally show, by means of experimental results, how the proposed analysis and parallelization approach leads to the design of efficient and high-performance FPGA-based implementations that are orders of magnitude faster than the state-of-the-art ones.
Bandwidth Optimization and Energy Management in Real-Time Wireless Networks
Authors: Franchino Gianluca , Buttazzo Giorgio , Marinoni Mauro 
Published: March 2016

In embedded systems operated by battery and interacting with the environment, a fundamental issue is the enforcement of real-time and energy constraints to guarantee a desired lifetime with a given performance. A lot of research has focused on energy management at the communication level; however, not many authors considered both real-time and energy requirements in wireless communication systems.
This article proposes El-SMan, a power-aware framework working in combination with MAC layer communication protocols for maximizing battery lifetime in wireless networks of embedded systems with real-time constraints. Exploiting the flexibility in bandwidth requirements, El-SMan adapts stream parameters to balance performance versus energy consumption, taking both lifetime and message deadlines into account.
Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells
Authors: Tang Chih-Hang Anthony , Zundell Joseph A. , Ranatunga Sujeewa , Lin Cindy , Nefedova Yulia , Del Valle Juan R. , Hu Chih-Chi Andrew 
Published: March 2016

Abstract
Endoplasmic reticulum (ER) stress responses through the IRE-1/XBP-1 pathway are required for the function of STING (TMEM173), an ER-resident transmembrane protein critical for cytoplasmic DNA sensing, IFN production, and cancer control. Here we show that the IRE-1/XBP-1 pathway functions downstream of STING and that STING agonists selectively trigger mitochondria-mediated apoptosis in normal and malignant B cells. Upon stimulation, STING was degraded less efficiently in B cells, implying that prolonged activation of STING can lead to apoptosis. Transient activation of the IRE-1/XBP-1 pathway partially protected agonist-stimulated malignant B cells from undergoing apoptosis. In Eμ-TCL1 mice with chronic lymphocytic leukemia, injection of the STING agonist 3′3′-cGAMP induced apoptosis and tumor regression. Similarly efficacious effects were elicited by 3′3′-cGAMP injection in syngeneic or immunodeficient mice grafted with multiple myeloma. Thus, in addition to their established ability to boost antitumoral immune responses, STING agonists can also directly eradicate malignant B cells. Cancer Res; 76(8); 2137–52. ©2016 AACR.
Development of a Novel c-MET–Based CTC Detection Platform
Authors: Zhang Tian , Boominathan Rengasamy , Foulk Brad , Rao Chandra , Kemeny Gabor , Strickler John H. , Abbruzzese James L. , Harrison Michael R. , Hsu David S. , Healy Patrick , Li Jing , Pi Cinthia , Prendergast Katherine M. , Hobbs Carey , Gemberling Sarah , George Daniel J. , Hurwitz Herbert I. , Connelly Mark , Garcia-Blanco Mariano A. , Armstrong Andrew J. 
Published: March 2016

Abstract
Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45+ leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%–80%) for c-MET–overexpressed cells, and specific (100%) for both c-MET–negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers.
Implications: This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability. Mol Cancer Res; 14(6); 539–47. ©2016 AACR.