bluuebunny/crossref_metadata_2025_split huggingface dataset:
The NeuroAiD Safe Treatment (NeST) Registry: a protocol
Authors: Venketasubramanian Narayanaswamy , Kumar Ramesh , Soertidewi Lyna , Abu Bakar Azizi , Laik Carine , Gan Robert 
Published: November 2015

IntroductionNeuroAiD (MLC601, MLC901), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries. The NeuroAiD Safe Treatment (NeST) Registry aims to assess its use and safety in the real-world setting.Methods and analysisThe NeST Registry is designed as a product registry that would provide information on the use and safety of NeuroAiD in clinical practice. An online NeST Registry was set up to allow easy entry and retrieval of essential information including demographics, medical conditions, clinical assessments of neurological, functional and cognitive state, compliance, concomitant medications, and side effects, if any, among patients on NeuroAiD. Patients who are taking or have been prescribed NeuroAiD may be included. Participation is voluntary. Data collected are similar to information obtained during standard care and are prospectively entered by the participating physicians at baseline (before initialisation of NeuroAiD) and during subsequent visits. The primary outcome assessed is safety (ie, non-serious and serious adverse event), while compliance and neurological status over time are secondary outcomes. The in-person follow-up assessments are timed with clinical appointments. Anonymised data will be extracted and collectively analysed. Initial target sample size for the registry is 2000. Analysis will be performed after every 500 participants entered with completed follow-up information.Ethics and disseminationDoctors who prescribe NeuroAiD will be introduced to the registry by local partners. The central coordinator of the registry will discuss the protocol and requirements for implementation with doctors who show interest. Currently, the registry has been approved by the Ethics Committees of Universiti Kebangsaan Malaysia (Malaysia) and National Brain Center (Indonesia). In addition, for other countries, Ethics Committee approval will be obtained in accordance with local requirements.Trial registration numberNCT02536079.
Implementing an institution-wide quality improvement policy to ensure appropriate use of continuous cardiac monitoring: a mixed-methods retrospective data analysis and direct observation study
Authors: Rayo Michael F , Mansfield Jerry , Eiferman Daniel , Mignery Traci , White Susan , Moffatt-Bruce Susan D 
Published: November 2015

BackgroundHospitals have been slow to adopt guidelines from the American Heart Association (AHA) limiting the use of continuous cardiac monitoring for fear of missing important patient cardiac events. A new continuous cardiac monitoring policy was implemented at a tertiary-care hospital seeking to monitor only those patients who were clinically indicated and decrease the number of false alarms in order to improve overall alarm response.MethodsLeadership support was secured, a cross-functional alarm management task force was created, and a system-wide policy was developed based on current AHA guidelines. Process measures, including cardiac monitoring rate, monitored transport rate, emergency department (ED) boarding rate and the percentage of false, unnecessary and true alarms, were measured to determine the policy's impact on patient care. Outcome measures, including length of stay and mortality rate, were measured to determine the impact on patient outcomes.ResultsCardiac monitoring rate decreased 53.2% (0.535 to 0.251 per patient day, p<0.001), monitored transport rate decreased 15.5% (0.216 to 0.182 per patient day, p<0.001), ED patient boarding rate decreased 36.6% (5.5% to 3.5% of ED patients, p<0.001) and the percentage of false alarms decreased (18.8% to 9.6%, p<0.001). Neither the length of stay nor mortality changed significantly after the policy was implemented.ConclusionsThe observed improvements in process measures coupled with no adverse effects to patient outcomes suggest that the overall system became more resilient to current and emerging demands. This study indicates that when collaboration across a diverse team is coupled with strong leadership support, policies and procedures such as this one can improve clinical practice and patient care.
Efficacy of psychotropic drugs in functional dyspepsia: systematic review and meta-analysis
Authors: Ford Alexander C , Luthra Pavit , Tack Jan , Boeckxstaens Guy E , Moayyedi Paul , Talley Nicholas J 
Published: November 2015

ObjectiveFunctional dyspepsia (FD) is a chronic gastroduodenal disorder. Individuals with FD demonstrate visceral hypersensitivity, abnormal central pain processing, and low mood, but it is unclear whether psychotropic drugs are an effective treatment for the condition. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs).DesignMEDLINE, EMBASE, EMBASE Classic, PsychINFO and the Cochrane Controlled Trials Register were searched (up to June 2015) for RCTs recruiting adults with FD comparing psychotropic drugs with placebo. We contacted authors directly to maximise trial eligibility and minimise risk of bias for studies. Dichotomous symptom data were pooled to obtain relative risk (RR) of remaining symptomatic after therapy, with 95% CIs.ResultsThe search identified 2795 citations; 13 RCTs (1241 patients) were eligible. Ten trials were at low risk of bias. The RR of FD symptoms not improving with psychotropic drugs versus placebo was 0.78 (95% CI 0.68 to 0.91) (number needed to treat=6; 95% CI 4 to 16). However, benefit was limited to antipsychotics and tricyclic antidepressants. When only studies that excluded individuals with coexistent mood disorder were considered, there was no benefit. Total numbers of adverse events and adverse events leading to withdrawal were significantly more common, with a number needed to harm of 21 for both.ConclusionsPsychotropic drugs may be an effective treatment for FD, but the effect appears to be limited to antipsychotics and tricyclic antidepressants with fewer trials for other agents, meaning that firm conclusions for efficacy cannot be made. More data from high quality RCTs are required to support their use in the treatment of FD.
Emergent mechanical thrombectomy for acute stroke using the Mindframe Capture LP system: initial single-center experience
Authors: Cerejo Russell , John Seby , Bauer Andrew , Hussain Muhammad S , Bain Mark , Rasmussen Peter , Hui Ferdinand , Masaryk Thomas , Toth Gabor 
Published: November 2015

BackgroundMechanical thrombectomy using stentrievers is the standard of care for emergent large vessel occlusion stroke. Data on the use of stentrievers in smaller caliber vessels are sparse.ObjectiveTo present our initial experience with the Mindframe Capture LP device, which was designed for mechanical thrombectomy in small cerebral arteries.MethodsA retrospective chart review was conducted of patients who underwent Mindframe device assisted emergent thrombectomy. Clinical, imaging, procedural and early follow-up data were obtained.ResultsNine patients met inclusion criteria (5 men, median age 62 years). Median National Institute of Health Stroke Scale (NIHSS) score was 18 (IQR 9–22), and 6 patients received intravenous tissue plasminogen activator. Six patients had M2 segment occlusions, and 2 patients had distal M1 segment occlusions of the middle cerebral artery. One had distal basilar artery occlusion. Median vessel diameter at the thrombus was 1.7 mm (IQR 1.5–2.5). In all 9 patients the Mindframe device was used together with manual aspiration, with median groin puncture to recanalization time of 35 min (IQR 27–54), and median procedural time of 67 min (IQR 51–91). Final Thrombolysis in Cerebral Infarction score was 3 and 2b in 4 patients each (89% total), and 2a in 1 patient. No patient had any postprocedural complications or symptomatic intracerebral hemorrhage. Median postprocedure and discharge NIHSS were 4 and 1, respectively.ConclusionsOur data suggest that the Mindframe device is safe and effective for rapid treatment of acute strokes involving small caliber intracranial vessels. Further study in a larger cohort is warranted.
Aneurysms in the target vessels of stroke patients subjected to mechanical thrombectomy: prevalence and impact on treatment
Authors: Zibold Felix , Kleine Justus F , Zimmer Claus , Poppert Holger , Boeckh-Behrens Tobias 
Published: November 2015

Background and purposeCoincidental aneurysms in the target vessels of stroke patients with large vessel occlusions (LVO) may pose risks during endovascular mechanical thrombectomy (MTE), but there are almost no data on this subject. Motivated by an incident of rupture of a hidden aneurysm induced by withdrawal of a stent retriever during a MTE procedure, this study examines the prevalence of aneurysms, associated complications, and implications for treatment strategies in patients with LVO stroke.MethodsA single-center retrospective analysis of angiographic and CT/MRI images and case records of 300 consecutive patients with LVO stroke treated with MTE was performed.ResultsAneurysms related to target vessels were detected in 11/300 patients, in 10/11 in the anterior circulation. In 9/11 patients the aneurysms were unknown prior to the stroke. The observed prevalence was >2-fold higher than expected for a healthy reference population. There was one complication (aneurysm rupture), as described above. In two subsequent patients with known aneurysms, MTE was conducted mainly with aspiration techniques which failed, contributing to a low recanalization rate in patients with aneurysm (45%).ConclusionsThe prevalence of aneurysms is relatively high in patients with LVO stroke, particularly in older, female, hypertensive patients, presumably reflecting overlapping risk factors. MTE should not be withheld from patients with LVO stroke with aneurysms, but particularly cautious approaches may be warranted. Further research in larger samples is required to obtain precise data on the prevalence and associated complication rates in MTE procedures. This is necessary to estimate the true risk and to tailor endovascular strategies in these patients.
Immunotargeting of Antigen xCT Attenuates Stem-like Cell Behavior and Metastatic Progression in Breast Cancer
Authors: Lanzardo Stefania , Conti Laura , Rooke Ronald , Ruiu Roberto , Accart Nathalie , Bolli Elisabetta , Arigoni Maddalena , Macagno Marco , Barrera Giuseppina , Pizzimenti Stefania , Aurisicchio Luigi , Calogero Raffaele Adolfo , Cavallo Federica 
Published: November 2015

Abstract
Resistance to therapy and lack of curative treatments for metastatic breast cancer suggest that current therapies may be missing the subpopulation of chemoresistant and radioresistant cancer stem cells (CSC). The ultimate success of any treatment may well rest on CSC eradication, but specific anti-CSC therapies are still limited. A comparison of the transcriptional profiles of murine Her2+ breast tumor TUBO cells and their derived CSC-enriched tumorspheres has identified xCT, the functional subunit of the cystine/glutamate antiporter system xc−, as a surface protein that is upregulated specifically in tumorspheres. We validated this finding by cytofluorimetric analysis and immunofluorescence in TUBO-derived tumorspheres and in a panel of mouse and human triple negative breast cancer cell-derived tumorspheres. We further show that downregulation of xCT impaired tumorsphere generation and altered CSC intracellular redox balance in vitro, suggesting that xCT plays a functional role in CSC biology. DNA vaccination based immunotargeting of xCT in mice challenged with syngeneic tumorsphere-derived cells delayed established subcutaneous tumor growth and strongly impaired pulmonary metastasis formation by generating anti-xCT antibodies able to alter CSC self-renewal and redox balance. Finally, anti-xCT vaccination increased CSC chemosensitivity to doxorubicin in vivo, indicating that xCT immunotargeting may be an effective adjuvant to chemotherapy. Cancer Res; 76(1); 62–72. ©2015 AACR.
PIK3CAH1047R Accelerates and Enhances KRASG12D-Driven Lung Tumorigenesis
Authors: Green Shon , Trejo Christy L. , McMahon Martin 
Published: November 2015

Abstract
KRAS-activating mutations drive human non–small cell lung cancer and initiate lung tumorigenesis in genetically engineered mouse (GEM) models. However, in a GEM model of KRASG12D-induced lung cancer, tumors arise stochastically following a latency period, suggesting that additional events are required to promote early-stage tumorigenic expansion of KRASG12D-mutated cells. PI3Kα (PIK3CA) is a direct effector of KRAS, but additional activation of PI3′-lipid signaling may be required to potentiate KRAS-driven lung tumorigenesis. Using GEM models, we tested whether PI3′-lipid signaling was limiting for the promotion of KRASG12D-driven lung tumors by inducing the expression of KRASG12D in the absence and presence of the activating PIK3CAH1047R mutation. PIK3CAH1047R expression alone failed to promote tumor formation, but dramatically enhanced tumorigenesis initiated by KRASG12D. We further observed that oncogenic cooperation between KRASG12D and PIK3CAH1047R was accompanied by PI3Kα-mediated regulation of c-MYC, GSK3β, p27KIP1, survivin, and components of the RB pathway, resulting in accelerated cell division of human or mouse lung cancer–derived cell lines. These data suggest that, although KRASG12D may activate PI3Kα by direct biochemical mechanisms, PI3′-lipid signaling remains rate-limiting for the cell-cycle progression and expansion of early-stage KRASG12D-initiated lung cells. Therefore, we provide a potential mechanistic rationale for the selection of KRAS and PIK3CA coactivating mutations in a number of human malignancies, with implications for the clinical deployment of PI3′ kinase–targeted therapies. Cancer Res; 75(24); 5378–91. ©2015 AACR.
The Inescapable Influence of Noncoding RNAs in Cancer
Authors: Adams Brian D. , Anastasiadou Eleni , Esteller Manel , He Lin , Slack Frank J. 
Published: November 2015

Abstract
This report summarizes information presented at the 2015 Keystone Symposium on “MicroRNAs and Noncoding RNAs in Cancer.” Nearly two decades after the discovery of the first miRNA, the role of noncoding RNAs in developmental processes and the mechanisms behind their dysregulation in cancer has been steadily elucidated. Excitingly, miRNAs have begun making their way into the clinic to combat diseases such as hepatitis C and various forms of cancer. Therefore, at this Keystone meeting, novel findings were presented that enhance our view on how small and long noncoding RNAs control developmental timing and oncogenic processes. Recurring themes included (i) how miRNAs can be differentially processed, degraded, and regulated by ribonucleoprotein complexes, (ii) how particular miRNA genetic networks that control developmental process, when disrupted, can result in cancer disease, (iii) the technologies available to therapeutically deliver RNA to combat diseases such as cancer, and (iv) the elucidation of the mechanism of actions for long noncoding RNAs, currently a poorly understood class of noncoding RNA. During the meeting, there was an emphasis on presenting unpublished findings, and the breadth of topics covered reflected how inescapable the influence of noncoding RNAs is in development and cancer. Cancer Res; 75(24); 5206–10. ©2015 AACR.
Prognostic Value of Flow‐Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta‐Analysis
Authors: Matsuzawa Yasushi , Kwon Taek‐Geun , Lennon Ryan J. , Lerman Lilach O. , Lerman Amir 
Published: November 2015

Background
Endothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow‐mediated dilation (FMD), and reactive hyperemia–‐peripheral arterial tonometry (RH‐PAT) for future cardiovascular events.

Methods and Results

Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH‐PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH‐PAT index (Ln_RHI) using random‐effects models. Thirty‐five FMD studies of 17 280 participants and 6 RH‐PAT studies of 1602 participants were included in the meta‐analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84–0.91],
P
<0.001, 0.1 increase in Ln_RHI 0.79 [0.71–0.87],
P
<0.001). There was significant heterogeneity in the magnitude of the association across studies. The magnitude of the prognostic value in cardiovascular disease subjects was comparable between these 2 methods; a 1 SD worsening in endothelial function was associated with doubled cardiovascular risk.

Conclusions
Noninvasive peripheral endothelial function tests, FMD and RH‐PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function–guided strategy can provide benefit in improving cardiovascular outcomes.
Identification of a Novel Heart–Liver Axis: Matrix Metalloproteinase‐2 Negatively Regulates Cardiac Secreted Phospholipase A
2
to Modulate Lipid Metabolism and Inflammation in the Liver
Authors: Hernandez‐Anzaldo Samuel , Berry Evan , Brglez Vesna , Leung Dickson , Yun Tae Jin , Lee Jun Seong , Filep Janos G. , Kassiri Zamaneh , Cheong Cheolho , Lambeau Gérard , Lehner Richard , Fernandez‐Patron Carlos 
Published: November 2015

Background

Endocrine functions of the heart have been well established. We investigated the hypothesis that cardiac secretion of a unique phospholipase A
2
recently identified by our laboratory (cardiac secreted phospholipase A
2
[
sPLA
2
]) establishes a heart–liver endocrine axis that is negatively regulated by matrix metalloproteinase‐2 (MMP‐2).

Methods and Results

In
Mmp2
−/−
mice, cardiac (but not hepatic)
sPLA
2
was elevated, leading to hepatic inflammation, immune cell infiltration, dysregulation of the sterol regulatory element binding protein‐2 and liver X receptor‐α pathways, abnormal transcriptional responses to dietary cholesterol, and elevated triglycerides in very low‐density lipoprotein and in the liver. Expression of monocyte chemoattractant protein‐3, a known MMP‐2 substrate, was elevated at both
mRNA
and protein levels in the heart. Functional studies including in vivo antibody neutralization identified cardiac monocyte chemoattractant protein 3 as a possible agonist of cardiac
sPLA
2
secretion. Conversely, systemic
sPLA
2
inhibition almost fully normalized the cardiohepatic phenotype without affecting monocyte chemoattractant protein‐3. Finally, wild‐type mice that received h
igh‐performance liquid chromatography
–isolated cardiac
sPLA
2
from
Mmp2

−/−

donors developed a cardiohepatic gene expression profile similar to that of
Mmp2

−/−

mice.

Conclusions

These findings identified the novel MMP‐2/cardiac
sPLA
2
pathway that endows the heart with important endocrine functions, including regulation of inflammation and lipid metabolism in the liver. Our findings could also help explain how

MMP
2

deficiency leads to cardiac problems, inflammation, and metabolic dysregulation in patients.
Nervus Intermedius Guides Auditory Brainstem Implant Surgery in Children with Cochlear Nerve Deficiency
Authors: Colletti Giacomo , Mandalà Marco , Colletti Liliana , Colletti Vittorio 
Published: November 2015

ObjectiveTo investigate the anatomic features of the nervus intermedius and cranial nerve VII in children with cochlear nerve deficiency and to verify whether the nervus intermedius can provide an additional landmark to help guide placement of the auditory brainstem implant electrode.Study DesignCase series with chart review.SettingTertiary referral center.Subjects and MethodsHigh‐definition video was captured during retrosigmoid surgery in 64 children (mean age, 3.91 ± 2.83 years) undergoing auditory brainstem implant placement. These videos were examined with particular reference to the number and variety of nervus intermedius bundles and any associated facial nerve anomalies.ResultsAbsence of cranial nerves VI, VII, and VIII was observed in 3, 6, and all 64 children, respectively. Fifteen children had several abnormalities of the facial nerve in the cerebellopontine angle. Anatomic identification of the facial nerve and the bundles composing the nervus intermedius was possible in 46 children. In 12 children, identification was possible with the assistance of intraoperative monitoring. The number of bundles composing the nervus intermedius varied from 1 to 6. The nervus intermedius and cranial nerve IX were useful landmarks for identifying the foramen of Luschka of the lateral recess.ConclusionThe nervus intermedius provides an additional landmark during auditory brainstem microsurgery since it was identified in all subjects. The nervus intermedius anatomy and its topographic relationship with the neurovascular structures around the foramen of Luschka have been described for the first time in children with cochlear nerve deficiency.
Innate Immune Response of the Pig Laryngeal Mucosa to Endotracheal Intubation
Authors: Hughes Owain R. , Ayling Sarah M. , Birchall Martin A. 
Published: November 2015

ObjectiveThe aim of this study was to measure the effects of endotracheal intubation on innate immune response within the pig laryngeal mucosa.Study DesignProspective controlled basic science study.SettingThe animal experiments and analyses were conducted at the University of Bristol.Samples and MethodsEighteen pigs, matched at the major histocompatibility complex (MHC), were used in the study. The pigs were divided into 9 pairs. One of each pair (9 pigs in total) was intubated with an endotracheal tube under general anesthesia for 90 minutes. Two days later, pinch biopsies were taken from the supraglottis (specifically the false cords) and subglottis of both pigs. The experiment was repeated 8 more times. Based on quantitative immunohistochemistry, percentage areas of positive staining for CD172a, CD163, MHC class II, CD14, and CD16 were calculated separately for the epithelium and lamina propria of each biopsy.ResultsTotal areas of laryngeal mucosa (epithelium and lamina propria) expressing CD172a and coexpressing CD163 and CD172a were significantly reduced at 2 days following endotracheal intubation (P=. 039 andP=. 037, respectively). MHC class II expression and MHC class II coexpression with CD172a were similarly reduced following intubation (P=. 003 andP=. 005, respectively). In the supraglottis, MHC class II coexpression with CD16 and CD14 was also reduced following endotracheal intubation (P=. 037).ConclusionsOur results indicate that endotracheal intubation reduces the number of innate immune cells within the upper airway mucosa. This may be an important first step in a cascade leading to chronic wound and scar formation causing airway stenosis.