bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating ischaemic stroke with intravenous tPA beyond 4.5 hours under the guidance of a MRI DWI/T2WI mismatch was safe and effective
Authors: Bai Qing-ke , Zhao Zhen-guo , Lu Lian-jun , Shen Jian , Zhang Jian-ying , Sui Hai-jing , Xie Xiu-hai , Chen Juan , Yang Juan , Chen Cui-rong 
Published: February 2019

PurposeClinical trials have provided evidence that treating patients with acute ischaemic stroke (AIS) beyond 4.5 hours was feasible. Among them using MRI diffusion-weighted imaging/fluid attenuation inversion response (DWI/FLAIR) mismatch to guide intravenous tissue plasminogen activator (tPA) was successful. Our study explored the outcome and safety of using DWI/T2-weighted imaging (T2WI) mismatch to guide intravenous tPA therapy for patients with AIS between 4.5 hours and 12 hours of onset.MethodThis was a retrospective study. Records of 1462 AIS patients with the time of onset of <12 hours were reviewed. Those had MRI rapid sequence study and had hyperintense signal on DWI but normal T2WI and received intravenous tPA up to 12 hours of onset were included in the analysis. Their demographics, risk factors, post-tPA complications, National Institutes of Health Stroke Scale (NIHSS) scores and outcome were recorded and analyse. χ2was used to compare the intergroup variables. SAS was used to perform statistical calculation. A p<0.05 was considered statistically significant.ResultsOf 1462 identified, 601 (41%) patients were entered into the final analysis. Among them, 327 (54%) had intravenous tPA within 4.5 hours of onset and 274 (46%) were treated between 4.5–12 hours. After intravenous tPA, 426 cases (71%) had >4 pints of improvement on NIHSS score within 24 hours. Postintravenous tPA, 32 (5.32%) cases had haemorrhagic transformation. 26 (4.33%) were asymptomatic ICH and 4 (0.67%) died. At 90 days, 523 (87%) achieved a modified Rankin scale of 0–2.ConclusionUsing MRI DWI/T2WI mismatch to identify patients with AIS for intravenous tPA between 4.5 hours and 12 hours was safe and effective. The outcome was similar to those used DWI/PWI or DWI/FLAIR mismatch as the screening tool. However, obtaining DWI/T2WI was faster and avoided the need of contrast material.
Association of smoking and electronic cigarette use with wheezing and related respiratory symptoms in adults: cross-sectional results from the Population Assessment of Tobacco and Health (PATH) study, wave 2
Authors: Li Dongmei , Sundar Isaac K , McIntosh Scott , Ossip Deborah J , Goniewicz Maciej Lukasz , O’Connor Richard J , Rahman Irfan 
Published: February 2019

BackgroundWheezing is a symptom of potential respiratory disease and known to be associated with smoking. Electronic cigarette use (‘vaping’) has increased exponentially in recent years. This study examined the cross-sectional association of vaping with wheezing and related respiratory symptoms and compare this association with smokers and dual users.MethodsThe Population Assessment of Tobacco and Health study wave 2 data collected from October 2014 to October 2015 with 28 171 adults were used. The cross-sectional association of vaping with self-reported wheezing and related respiratory symptoms relative to smokers and dual users of tobacco and electronic cigarettes were studied using multivariable logistic and cumulative logistic regression models with consideration of complex sampling design.ResultsAmong the 28 171 adult participants, 641 (1.2%) were current vapers who used e-cigarettes exclusively, 8525 (16.6%) were current exclusive smokers, 1106 (2.0%) were dual users and 17 899 (80.2%) were non-users. Compared with non-users, risks of wheezing and related respiratory symptoms were significantly increased in current vapers (adjusted OR (aOR)=1.67, 95% CI: 1.23 to 2.15). Current vapers had significantly lower risk in wheezing and related respiratory symptoms compared with current smokers (aOR=0.68, 95% CI: 0.53 to 0.87). No significant differences were found between dual users and current smokers in risk of wheezing and related respiratory symptoms (aOR=1.06, 95% CI: 0.91 to 1.24).ConclusionsVaping was associated with increased risk of wheezing and related respiratory symptoms. Current vapers had lower risk in wheezing and related respiratory symptoms than current smokers or dual users but higher than non-users. Both dual use and smoking significantly increased the risk of wheezing and related respiratory symptoms.
On the number of subgroups of non-metacyclic minimal non-abelian p-groups
Authors: Kumar Pradeep , Jain Vivek Kumar 
Published: February 2019

In this paper, we find the number of subgroups in non-metacyclic minimal non-abelian [Formula: see text]-groups, [Formula: see text] an odd prime. In particular, we study a problem introduced by Berkovich [Groups of Prime Power Order, Vol. III (Walter de Gruyter, Berlin, New York, 2011)].
DreamWeaver
Authors: Meisner David , Wenisch Thomas F. 
Published: February 2019

Numerous data center services exhibit low average utilization leading to poor energy efficiency. Although CPU voltage and frequency scaling historically has been an effective means to scale down power with utilization, transistor scaling trends are limiting its effectiveness and the CPU is accounting for a shrinking fraction of system power. Recent research advocates the use of full-system idle low-power modes to combat energy losses, as such modes provide the deepest power savings with bounded response time impact. However, the trend towards increasing cores per die is undermining the effectiveness of these sleep modes, particularly for request-parallel data center applications, because the independent idle periods across individual cores are unlikely to align by happenstance.
We propose DreamWeaver, architectural support to facilitate deep sleep for request-parallel applications on multicore servers. DreamWeaver comprises two elements: Weave Scheduling, a scheduling policy to coalesce idle and busy periods across cores to create opportunities for system-wide deep sleep; and the Dream Processor, a light-weight co-processor that monitors incoming network traffic and suspended work during sleep to determine when the system must wake. DreamWeaver is based on two key concepts: (1) stall execution and sleep anytime any core is unoccupied, but (2) constrain the maximum time any request may be stalled. Unlike prior scheduling approaches, DreamWeaver will preempt execution to sleep, maximizing time spent at the systems' most efficient operating point. We demonstrate that DreamWeaver can smoothly trade-off bounded, predictable increases in 99th-percentile response time for increasing power savings, and strictly dominates the savings available with voltage and frequency scaling and timeout-based request batching schemes.
Respiratory system reactance reflects communicating lung volume in chronic obstructive pulmonary disease
Authors: Milne Stephen , Jetmalani Kanika , Chapman David G. , Duncan Joseph M. , Farah Claude S. , Thamrin Cindy , King Gregory G. 
Published: February 2019

Respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) is theoretically and experimentally related to lung volume. In chronic obstructive pulmonary disease (COPD), the absolute volume measured by body plethysmography includes a proportion that is inaccessible to pressure oscillations applied via the mouth, that is, a “noncommunicating” lung volume. We hypothesized that in COPD the presence of noncommunicating lung would disrupt the expected Xrs-volume relationship compared with plethysmographic functional residual capacity (FRCpleth). Instead, Xrs would relate to estimates of communicating volume, namely, expiratory reserve volume (ERV) and single-breath alveolar volume (VaSB). We examined FOT and lung function data from people with COPD ( n = 51) and from healthy volunteers ( n = 40). In healthy volunteers, we observed an expected inverse relationship between reactance at 5 Hz (X5) and FRCpleth. In contrast, there was no such relationship between X5 and FRCplethin COPD subjects. However, there was an inverse relationship between X5 and both ERV and VaSB. Hence the theoretical Xrs-volume relationship is present in COPD but only when considering the communicating volume rather than the absolute lung volume. These findings confirm the role of reduced communicating lung volume as an important determinant of Xrs and therefore advance our understanding and interpretation of FOT measurements in COPD.NEW & NOTEWORTHY To investigate the determinants of respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) in chronic obstructive pulmonary disease (COPD), we examine the relationship between Xrs and lung volume. We show that Xrs does not relate to absolute lung volume (functional residual capacity) in COPD but instead relates only to the volume of lung in communication with the airway opening. This communicating volume may therefore be fundamental to our interpretation of FOT measurements in COPD and other pulmonary diseases.
Tidal breathing flow volume profiles during sleep in wheezing infants measured by impedance pneumography
Authors: Gracia-Tabuenca Javier , Seppä Ville-Pekka , Jauhiainen Milla , Kotaniemi-Syrjänen Anne , Malmström Kristiina , Pelkonen Anna , Mäkelä Mika , Viik Jari , Malmberg L. Pekka 
Published: February 2019

Overnight analysis of tidal breathing flow volume (TBFV) loops, recorded by impedance pneumography (IP), has been successfully applied in the home monitoring of children with wheezing disorders. However, little is known on how sleep physiology modifies the relationship between TBFV profiles and wheeze. We studied such interactions in wheezing infants. Forty-three infants recruited because of recurrent lower airway symptoms were divided into three groups based on their risk of asthma: high (HR), intermediate (IR), or low (LR). Sedated patients underwent infant lung function testing including assessment of airway responsiveness to methacholine at the hospital and a full-night recording of TBFV profiles at home with IP during natural sleep. Overnight TBFV indexes were estimated from periods of higher and lower respiration variability, presumably belonging to active [rapid eye movement (REM)] and quiet [non-REM (NREM)] sleep, respectively. From 35 valid recordings, absolute time indexes showed intrasubject sleep phase differences. Peak flow relative to time and volume was lower in HR compared with LR only during REM, suggesting altered expiratory control. Indexes estimating the concavity/convexity of flow decrease during exhalation suggested limited flow during passive exhale in HR compared with IR and LR, similarly during NREM and REM. Moreover, during REM convexity was negatively correlated with maximal flow at functional residual capacity and methacholine responsiveness. We conclude that TBFV profiles determined from overnight IP recordings vary because of sleep phase and asthma risk. Physiological changes during REM, most likely decrease in respiratory muscle tone, accentuate the changes in TBFV profiles caused by airway obstruction. NEW & NOTEWORTHY Impedance pneumography was used to investigate overnight tidal breathing flow volume (TBFV) indexes and their interactions with sleep phase [rapid eye movement (REM) vs. non-REM] at home in wheezing infants. The study shows that TBFV indexes vary significantly because of sleep phase and asthma risk of the infant and that during REM the changes in TBFV indexes caused by airway obstruction are accentuated and better associated with lung function of the infant.
Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells
Authors: Takeda Mitsunobu , Koseki Jun , Takahashi Hidekazu , Miyoshi Norikatsu , Nishida Naohiro , Nishimura Junichi , Hata Taishi , Matsuda Chu , Mizushima Tsunekazu , Yamamoto Hirofumi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Haraguchi Naotsugu 
Published: February 2019

Abstract

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSCs remains promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSCs and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an antimalarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug. Endolysosomal RAB5/7 and LAMP1/2 mediated parkin-dependent mitochondrial clearance and modulated mitophagy through lysosomal dynamics. In a patient-derived xenograft (PDX) model of colon cancer, treatment with mefloquine resulted in suppression of mitophagic PINK1/PARKIN and increased mitochondrial disorder and mitochondria-induced apoptosis without apparent side effects. These results suggest that the combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs.

Significance:
These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.
Deoxyribozymes as Catalytic Nanotherapeutic Agents
Authors: Khachigian Levon M. 
Published: February 2019

Abstract
RNA-cleaving deoxyribozymes (DNAzymes) are synthetic single-stranded DNA-based catalytic molecules that can be engineered to bind to and cleave target mRNA at predetermined sites. These have been used as therapeutic agents in a range of preclinical cancer models and have entered clinical trials in Europe, China, and Australia. This review surveys regulatory insights into mechanisms of disease brought about by use of catalytic DNA in vitro and in vivo, including recent uses as nanosensors, nanoflowers, and nanosponges, and the emerging role of adaptive immunity underlying DNAzyme inhibition of cancer growth. DNAzymes represent a promising new class of nucleic acid–based therapeutics in cancer. This article discusses mechanistic and therapeutic insights brought about by DNAzyme use as nanotools and reagents in a range of basic science, experimental therapeutic and clinical applications. Current limitations and future perspectives are also discussed.
Impact of Concomitant Administration of Gastric Acid–Suppressive Agents and Pazopanib on Outcomes in Soft-Tissue Sarcoma Patients Treated within the EORTC 62043/62072 Trials
Authors: Mir Olivier , Touati Nathan , Lia Michela , Litière Saskia , Le Cesne Axel , Sleijfer Stefan , Blay Jean-Yves , Leahy Michael , Young Robin , Mathijssen Ron H.J. , Van Erp Nielka P. , Gelderblom Hans , Van der Graaf Winette T. , Gronchi Alessandro 
Published: February 2019

Abstract

Purpose:
Pazopanib is active in soft-tissue sarcoma (STS). Because pazopanib absorption is pH-dependent, coadministration with gastric acid–suppressive (GAS) agents such as proton pump inhibitors could affect exposure of pazopanib, and thereby its therapeutic effects.

Patients and Methods:
The EORTC 62043 and 62072 were single-arm phase II and placebo-controlled phase III studies, respectively, of pazopanib in advanced STS. We first compared the outcome of patients treated with pazopanib with or without GAS agents for ≥80% of treatment duration, and subsequently using various thresholds. The impact of concomitant GAS therapy was assessed on progression-free survival (PFS) and overall survival (OS) using multivariate Cox models, exploring and comparing also the potential effect on placebo-treated patients.

Results:
Of 333 eligible patients, 59 (17.7%) received concomitant GAS therapy for &gt;80% of pazopanib treatment duration. Median PFS was shorter in GAS therapy users versus nonusers: 2.8 vs. 4.6 months, respectively [HR, 1.49; 95% confidence interval (CI), 1.11–1.99; P = 0.01]. Concomitant administration of GAS therapy was also associated with a shorter median OS: 8.0 vs. 12.6 months (HR, 1.81; 95% CI, 1.31–2.49; P &lt; 0.01). The longer the overlapping use of GAS agents and pazopanib, the worse the outcome with pazopanib. These effects were not observed in placebo-treated patients (HR, 0.82; 95% CI, 0.51–1.34; P = 0.43 for PFS and HR, 0.84; 95% CI, 0.48–1.48; P = 0.54 for OS).

Conclusions:
Coadministration of long-term GAS therapy with pazopanib was associated with significantly shortened PFS and OS. Withdrawal of GAS agents must be considered whenever possible. Therapeutic drug monitoring of pazopanib plasma concentrations may be helpful for patients on pazopanib and GAS therapy.
Low Levels of Serum β-Carotene and β-Carotene/Retinol Ratio Are Associated with Histological Severity in Nonalcoholic Fatty Liver Disease Patients
Authors: Wang Lijun , Ding Chenghe , Zeng Fangfang , Zhu Huilian 
Published: February 2019

β-Carotene has been reported to alleviate hepatic steatosis (SS), inflammation, and fibrosis in vivo and vitro studies. However, the clinical relevance of serum β-carotene and β-carotene-to-retinol (SC/SR) ratio with histological severity in nonalcoholic fatty liver disease (NAFLD) patients is unknown. This case-control study enrolled 24 control subjects and 62 NAFLD patients. Liver biopsies were collected and histological characteristics were assessed. Information with regard to demographic, anthropometric and dietary intake was assessed by face-to-face interviews with questionnaire. Serum β-carotene and retinol concentrations were determined by the HPLC method. Serum β-carotene and SC/SR levels in NAFLD patients were significantly lower than these in controls (0.23 ± 0.01 vs. 0.35 ± 0.04 μmol/L, 0.38 ± 0.03 vs. 0.84 ± 0.10). Compared with individuals without SS, both β-carotene and SC/SR levels were significantly decreased in those with moderate SS (0.34 ± 0.03 vs. 0.21 ± 0.02 μmol/L, 0.76 ± 0.09 vs. 0.37 ± 0.05). Subjects with mild inflammation had a significantly lower β-carotene and SC/SR levels than those without inflammation (0.23 ± 0.01 vs. 0.33 ± 0.04 μmol/L, 0.77 ± 0.09 vs. 0.38 ± 0.03). Serum SC/SR was significantly lower in patients with mild fibrosis than those without fibrosis (0.45 [0.27–0.83] vs. 0.34 [0.26–0.51]). According to the NAFLD Activity Scoring score, both β-carotene and SC/SR gradually decreased with disease progression from normal liver, simple SS to steatohepatitis borderline (<i>p</i><sub>trend</sub> ≤ 0.001). These results show that NAFLD patients have lower circulating β-carotene concentration and SC/SR ratio, which are associated with the histological severity of NAFLD.
Impact of Initial Shunt Type on Echocardiographic Indices in Children After Single Right Ventricle Palliations
Authors: Frommelt Peter C. , Hu Chenwei , Trachtenberg Felicia , Baffa Jeanne Marie , Boruta Richard J. , Chowdhury Shahryar , Cnota James F. , Dragulescu Andreea , Levine Jami C. , Lu Jimmy , Mercer-Rosa Laura , Miller Thomas A. , Shah Amee , Slesnick Timothy C. , Stapleton Gary , Stelter Jessica , Wong Pierre , Newburger Jane W. ,   for the Pediatric Heart Network Investigators
Published: February 2019

Background
Heart size and function in children with single right ventricle (RV) anomalies may be influenced by shunt type at the Norwood procedure. We sought to identify shunt-related differences during early childhood after staged surgical palliations using echocardiography.

Methods
We compared echocardiographic indices of RV, neoaortic, and tricuspid valve size and function at 14 months, pre-Fontan, and 6 years in 241 subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt or RV-to-pulmonary-artery shunt.

Results
At 6 years, the shunt groups did not differ significantly in any measure except for increased indexed neoaortic area in the modified Blalock-Taussig shunt. RV ejection fraction improved between pre-Fontan and 6 years in the RV-to-pulmonary artery shunt group but was stable in the modified Blalock-Taussig shunt group. For the entire cohort, RV diastolic and systolic size and functional indices were improved at 6 years compared with earlier measurements, and indexed tricuspid and neoaortic annular area decreased from 14 months to 6 years. The prevalence of ≥moderate tricuspid and neoaortic regurgitation was uncommon and did not vary by group or time period. Diminished RV ejection fraction at the 14-month study was predictive of late death/transplant; the hazard of late death/transplant when RV ejection fraction was <40% was tripled (hazard ratio, 3.18; 95% CI, 1.41–7.17).

Conclusions
By 6 years after staged palliation, shunt type has not impacted RV size and function, and RV and valvar size and function show beneficial remodeling. Poor RV systolic function at 14 months predicts worse late survival independent of the initial shunt type.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00115934.
Bioprosthetic Aortic Valve Replacement in Nonelderly Adults
Authors: Etnel Jonathan R.G. , Huygens Simone A. , Grashuis Pepijn , Pekbay Begüm. , Papageorgiou Grigorios , Roos Hesselink Jolien W. , Bogers Ad J.J.C. , Takkenberg Johanna J.M. 
Published: February 2019

Background:
To support decision-making in aortic valve replacement in nonelderly adults, we aim to provide a comprehensive overview of reported outcome after bioprosthetic aortic valve replacement and to translate this to age-specific patient outcome estimates.

Methods and Results:
A systematic review was conducted for papers reporting clinical outcome after aortic valve replacement with currently available bioprostheses in patients with a mean age <55 years, published between January 1, 2000, and January 9, 2016. Pooled reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risk for the ages of 25, 35, 45, and 55 years at surgery. Nineteen publications were included, encompassing a total of 2686 patients with 21 117 patient-years of follow-up (pooled mean follow-up: 7.9±4.2 years). Pooled mean age at surgery was 50.7±11.0 years. Pooled early mortality risk was 3.30% (95% CI, 2.39–4.55), late mortality rate was 2.39%/y (95% CI, 1.13–2.94), reintervention 1.82%/y (95% CI, 1.31–2.52), structural valve deterioration 1.59%/y (95% CI, 1.21–2.10), thromboembolism 0.53%/y (95% CI, 0.42–0.67), bleeding 0.22%/y (95% CI, 0.16–0.32), endocarditis 0.48%/y (95% CI, 0.37–0.62), and 20-year pooled actuarial survival was 58.7% and freedom from reintervention was 29.0%. Median time to structural valve deterioration was 17.3 years and median time to all-cause first reintervention was 16.9 years. For a 45-year-old adult, for example, this translated to a microsimulation-based estimated life expectancy of 21 years (general population: 32 years) and lifetime risk of reintervention of 78%, structural valve deterioration 71%, thromboembolism 12%, bleeding 5%, and endocarditis 9%.

Conclusions:
Aortic valve replacement with bioprostheses in young adults is associated with high structural valve deterioration and reintervention rates and low, though not absent, hazards of thromboembolism and bleeding. Foremostly, most patients will require one or more reinterventions during their lifetime and survival is impaired in comparison with the age- and sex-matched general population. Prosthesis durability remains the main concern in nonelderly patients.