bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative ischemic events in patients undergoing carotid artery stenting using algorithmic selection for embolic protection
Authors: Kawabata Yasuhiro , Nakajima Norio , Miyake Hidenori , Fukuda Shunichi , Tsukahara Tetsuya 
Published: April 2019

Purpose Carotid artery stenting (CAS) is a valuable alternative to carotid endarterectomy, especially in high-risk patients. However, the reported incidences of perioperative stroke and death remain higher than for carotid endarterectomy, even when using embolic protection devices (EPDs) during CAS. Our purpose was to evaluate 30-day major adverse events after CAS when selecting the most appropriate EPD. Methods We reviewed the clinical outcomes of 61 patients with 64 lesions who underwent CAS with EPDs. Patients who underwent CAS associated with thrombectomy and who had a preoperative modified Rankin scale score >3 were excluded from the analysis. The EPD was selected based on symptoms, carotid wall magnetic resonance imaging and lesion length, and we analyzed combined 30-day complication rates (transient ischemic attack, minor stroke, major stroke or death). Results Forty-nine patients were men and 12 were women. The median age was 72 years (range: 59–89 years) and 44 lesions were asymptomatic. A filter-type EPD was selected in 23 procedures, distal-balloon protection in 14 procedures and proximal-occlusive protection in 27 procedures. Two patients (3.1%) experienced a transient ischemic attack and one patient (1.6%) had a minor stroke within 30 days of the procedure. No patients experienced procedure-related morbidities (modified Rankin score >2) or death. Conclusions The perioperative stoke rate was low when we selected a proximal-occlusive-type EPD in high-risk patients with vulnerable carotid artery disease. Our algorithm for EPD selection was an effective tool in the perioperative management of carotid artery stenosis.
Intensive Care Unit Admission Following Surgery for Pediatric Spinal Deformity: An Analysis of the ACS-NSQIP Pediatric Spinal Fusion Procedure Targeted Dataset
Authors: Malik Azeem Tariq , Yu Elizabeth , Kim Jeffery , Khan Safdar N. 
Published: April 2019

Study Design: Retrospective cohort. Objective: To understand which patient and surgical factors are predictive of an increased odds of undergoing an admission and a prolonged stay >2 days in an intensive care unit (ICU) following corrective surgery for pediatric deformity. Methods: The 2016 American College of Surgeons–National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric Spinal Fusion Procedure Targeted database records, merged with original 2016 ACS-NSQIP Pediatric file variables, were used for this study. Univariate and multivariate analyses were used to identify independent risk factors associated with admission, as well as a prolonged length of stay in the ICU following surgery. Results: A total of 1398 (39.5%) patients required an ICU admission following the procedure—out of whom 416 (29.8%) stayed for more than 2 days. Following adjusted analysis, patient and surgical factors independently associated with an ICU admission were black/African American versus white race, anterior fusion, combined fusion, nonidiopathic scoliosis, preoperative ventilator dependence, asthma, having structural pulmonary abnormality, developmental delay, having a neuromuscular disorder, requiring nutritional support and a total operative time >270 minutes. The only significant factors associated with a prolonged length of ICU stay >2 days were preoperative ventilator dependence, nutritional support requirement, and undergoing anterior or combined fusion. Conclusions: This study is the first of its kind to identify significant patient- and procedure-level factors associated with an ICU admission, and also explores predictors for a prolonged stay in the ICU. Surgeons can use this data to preoperatively counsel families and ensure postoperative course of care is appropriately planned ahead of time.
Posterior circulation stroke diagnosis using HINTS in patients presenting with acute vestibular syndrome: A systematic review
Authors: Krishnan Kailash , Bassilious Kerolos , Eriksen Erik , Bath Philip M , Sprigg Nikola , Brækken Sigrun Kierulf , Ihle-Hansen Hege , Horn Morten Andreas , Sandset Else Charlotte 
Published: April 2019

Purpose Acute vestibular syndrome – vertigo, nausea/vomiting, nystagmus and gait unsteadiness – is common, and differentiating posterior circulation stroke from a peripheral cause can be challenging. The National Institute of Health Stroke Scale (NIHSS) does not include acute vestibular syndrome, and early computed tomography scanning cannot rule out acute ischaemia. A positive Head Impulse–Nystagmus–Test of Skew (HINTS) test suggests posterior circulation stroke in acute vestibular syndrome when any of three signs are present: normal horizontal head impulse, gaze-direction nystagmus or eye skew deviation. This systematic review examined the accuracy of positive HINTS in identifying posterior circulation stroke in acute vestibular syndrome patients. Methods We searched MEDLINE (1966 to 21 December 2017), EMBASE (1980 to December 2017), Web of Science and scanned bibliographies. Two authors independently screened relevant articles and extracted data. We included studies where HINTS was used to identify posterior circulation stroke with diagnosis confirmed using magnetic resonance imaging. Findings Six studies (n = 644 patients) were identified. Acute stroke was confirmed in 200 (31.1%) patients. There was a 15-fold increased risk of posterior circulation stroke in patients with positive HINTS test compared to those with no abnormality (RR: 15.84, 95% CI: 5.25–47.79). For any stroke, the pooled sensitivity was 95.5% (95% CI: 92.6–98.4%) and specificity was 71.2% (95% CI: 67.0–75.4%). Discussion and Conclusion The data suggest that the HINTS test as one element of clinical evaluation is useful to differentiate posterior circulation stroke from peripheral causes in acute vestibular syndrome. Further studies are needed to validate HINTS as a clinical prediction tool in emergency department settings and selection of patients for reperfusion treatment.
Glia maturation factor-γ regulates murine macrophage iron metabolism and M2 polarization through mitochondrial ROS
Authors: Aerbajinai Wulin , Ghosh Manik C. , Liu Jie , Kumkhaek Chutima , Zhu Jianqing , Chin Kyung , Rouault Tracey A. , Rodgers Griffin P. 
Published: April 2019

AbstractIn macrophages, cellular iron metabolism status is tightly integrated with macrophage phenotype and associated with mitochondrial function. However, how molecular events regulate mitochondrial activity to integrate regulation of iron metabolism and macrophage phenotype remains unclear. Here, we explored the important role of the actin-regulatory protein glia maturation factor-γ (GMFG) in the regulation of cellular iron metabolism and macrophage phenotype. We found that GMFG was downregulated in murine macrophages by exposure to iron and hydrogen peroxide. GMFG knockdown altered the expression of iron metabolism proteins and increased iron levels in murine macrophages and concomitantly promoted their polarization toward an anti-inflammatory M2 phenotype. GMFG-knockdown macrophages exhibited moderately increased levels of mitochondrial reactive oxygen species (mtROS), which were accompanied by decreased expression of some mitochondrial respiration chain components, including the iron-sulfur cluster assembly scaffold protein ISCU as well as the antioxidant enzymes SOD1 and SOD2. Importantly, treatment of GMFG-knockdown macrophages with the antioxidant N-acetylcysteine reversed the altered expression of iron metabolism proteins and significantly inhibited the enhanced gene expression of M2 macrophage markers, suggesting that mtROS is mechanistically linked to cellular iron metabolism and macrophage phenotype. Finally, GMFG interacted with the mitochondrial membrane ATPase ATAD3A, suggesting that GMFG knockdown–induced mtROS production might be attributed to alteration of mitochondrial function in macrophages. Our findings suggest that GMFG is an important regulator in cellular iron metabolism and macrophage phenotype and could be a novel therapeutic target for modulating macrophage function in immune and metabolic disorders.
RETRACTED ARTICLE: Large tumor suppressor kinase 2 overexpression attenuates 5-FU-resistance in colorectal cancer via activating the JNK-MIEF1-mitochondrial division pathway
Authors: Yao Weilong , Zhu Shengtao , Li Peng , Zhang Shutian 
Published: April 2019

Abstract
Background
5-Fluorouracil (5-FU) is a standard treatment for colorectal cancer, but most patients develop 5-FU resistance. Here, we conducted experiments to identify an effective approach to augment 5-FU-based treatment in colorectal cancer in vitro.

Methods
SW480 cells were in the present study and treated with 5-FU. Besides, LATS2 adenovirus vectors were infected into SW480 cells. Western blotting, immunofluorescence and ELISA were used to evaluate cell death and mitochondrial function. Pathway blocker was used to verify the role of MAPK-JNK pathway in SW480 cell death.

Results
An obvious drop in large tumor suppressor kinase 2 (LATS2) expression was observed in SW480 cells after treatment with 5-FU. In addition, upregulation of LATS2 expression through infection with LATS2 adenovirus further increased the reduction of SW480 cell viability induced by 5-FU. Functional exploration showed that 5-FU treatment suppressed mitochondrial membrane potential, enhanced cyt-c release into the nucleus, induced an oxidative injury environment by promoting ROS production, and eventually upregulated Bax-related mitochondrial apoptosis. Besides, LATS2 overexpression in combination with 5-FU treatment further perturbed mitochondrial homeostasis, and this effect was achieved by elevating mitochondrial division. Mechanistically, LATS2 overexpression and 5-FU co-treatment amplified mitochondrial division by upregulating MIEF1 expression in a manner dependent on MAPK-JNK axis. Knockdown of MIEF1 using an siRNA-mediated loss of function assay and/or inhibition of the MAPK-JNK pathway using the specific inhibitor SP600125 abolished LATS2/5-FU-mediated deleterious effects on mitochondrial performance and SW480 cell viability.

Conclusions
In light of the above findings, LATS2 downregulation could be a potential mechanism of low response to 5-FU treatment. Overexpression of LATS2 to further disrupt mitochondrial function via the JNK-MIEF1 signalling pathway might be a method to optimize 5-FU-based chemotherapy.
The use of urea for the treatment of onychomycosis: a systematic review
Authors: Dars S. , Banwell H. A. , Matricciani L. 
Published: April 2019

AbstractBackgroundOnychomycosis, a fungal infection affecting the nail plate, is a common condition often requiring prolonged treatment regimens, with low success rates. Urea is one treatment option, which is thought to improve the efficacy of topical and oral antifungal agents. Despite a theoretical basis for the use of urea for the treatment of onychomycosis, the evidence‐base for this treatment has not been systematically reviewed.AimThe purpose of this study was to conduct a systematic literature review to determine the efficacy and safety of urea as a monotherapy and as adjunct therapy, compared to other treatment regimens for onychomycosis.MethodA systematic literature search of ten electronic databases was conducted. Only studies that used microscopy and culture or other validated laboratory‐based testing method to confirm the presence of a fungal infection before treatment were included. The outcome measures assessed were efficacy (defined in terms of mycological, clinical and complete cure) and safety (defined as self‐reported adverse events).ResultsThe systematic search yielded 560 unique studies for review. Of these, only six were eligible for inclusion. All studies were observed to have methodological concerns, most studies consisted of small sample sizes and were difficult to compare given heterogeneity in outcome measures and follow‐up time. Despite this, a trend was observed to suggest that urea, when added to topical or oral antifungal treatment regimens, improved efficacy of the treatment.ConclusionThis review suggests that topical urea, as an adjunct to topical and oral antifungal treatment regimens, may improve the efficacy of treatment. However, further research is needed.
Association of glucose and blood pressure variability on oxidative stress in patients with type 2 diabetes mellitus and hypertension: a cross-sectional study
Authors: Ohara Makoto , Kohata Yo , Nagaike Hiroe , Koshibu Masakazu , Gima Hiroya , Hiromura Munenori , Yamamoto Takeshi , Mori Yusaku , Hayashi Toshiyuki , Fukui Tomoyasu , Hirano Tsutomu 
Published: April 2019

Abstract
Background
The present study evaluated the effects of glucose and blood pressure (BP) variability on oxidative stress in patients with type 2 diabetes mellitus (T2DM) and hypertension.

Methods
A total of 60 inpatients with T2DM underwent continuous glucose monitoring (CGM) and ambulatory BP monitoring (ABPM). Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Glucose variability, mean glucose level, percentage coefficient of variation for glucose, mean amplitude of glycemic excursions (MAGE), and area under the postprandial plasma glucose curve were determined through CGM. BP variability was assessed by measuring average BP, standard deviation (SD) of systolic and diastolic BP, and coefficient of variation (CV) of systolic and diastolic BP during daytime and nighttime ABPM.

Results
Participants had a mean age of 64.5 ± 13.3 years with the duration of the disease 13.9 ± 12.4 years and HbA1c of 8.5 ± 1.2%. Univariate analysis showed that MAGE, nighttime SDs of systolic and diastolic BP, and nighttime CV of systolic BP were significantly correlated with d-ROMs. Further, stepwise multiple regression analysis identified MAGE, nighttime SD and CV of diastolic BP, estimated glomerular filtration rate, and smoking as independent contributors to d-ROMs.

Conclusions
Oxidative stress was associated with daily glucose and nighttime diastolic BP variability in patients with T2DM and hypertension.
Trial registration UMIN Clinical Trial Registry UMIN000035615, Registered January 22, 2019—retrospectively registered
Emerin anchors Msx1 and its protein partners at the nuclear periphery to inhibit myogenesis
Authors: Ma Zhangjing , Shi Huiyuan , Shen Yi , Li Huixia , Yang Yu , Yang Jiange , Zhao Hui , Wang Gang , Wang Jingqiang 
Published: April 2019

Abstract
Background
Previous studies have shown that in myogenic precursors, the homeoprotein Msx1 and its protein partners, histone methyltransferases and repressive histone marks, tend to be enriched on target myogenic regulatory genes at the nuclear periphery. The nuclear periphery localization of Msx1 and its protein partners is required for Msx1’s function of preventing myogenic precursors from pre-maturation through repressing target myogenic regulatory genes. However, the mechanisms underlying the maintenance of Msx1 and its protein partners’ nuclear periphery localization are unknown.

Results
We show that an inner nuclear membrane protein, Emerin, performs as an anchor settled at the inner nuclear membrane to keep Msx1 and its protein partners Ezh2, H3K27me3 enriching at the nuclear periphery, and participates in inhibition of myogenesis mediated by Msx1. Msx1 interacts with Emerin both in C2C12 myoblasts and mouse developing limbs, which is the prerequisite for Emerin mediating the precise location of Msx1, Ezh2, and H3K27me3. The deficiency of Emerin in C2C12 myoblasts disturbs the nuclear periphery localization of Msx1, Ezh2, and H3K27me3, directly indicating Emerin functioning as an anchor. Furthermore, Emerin cooperates with Msx1 to repress target myogenic regulatory genes, and assists Msx1 with inhibition of myogenesis.

Conclusions
Emerin cooperates with Msx1 to inhibit myogenesis through maintaining the nuclear periphery localization of Msx1 and Msx1’s protein partners.
Improved multiobjective salp swarm optimization for virtual machine placement in cloud computing
Authors: Alresheedi Shayem Saleh , Lu Songfeng , Abd Elaziz Mohamed , Ewees Ahmed A. 
Published: April 2019

Abstract
In data center companies, cloud computing can host multiple types of heterogeneous virtual machines (VMs) and provide many features, including flexibility, security, support, and even better maintenance than traditional centers. However, some issues need to be considered, such as the optimization of energy usage, utilization of resources, reduction of time consumption, and optimization of virtual machine placement. Therefore, this paper proposes an alternative multiobjective optimization (MOP) approach that combines the salp swarm and sine-cosine algorithms (MOSSASCA) to determine a suitable solution for virtual machine placement (VMP). The objectives of the proposed MOSSASCA are to maximize mean time before a host shutdown (MTBHS), to reduce power consumption, and to minimize service level agreement violations (SLAVs). The proposed method improves the salp swarm and the sine-cosine algorithms using an MOP technique. The SCA works by using a local search approach to improve the performance of traditional SSA by avoiding trapping in a local optimal solution and by increasing convergence speed. To evaluate the quality of MOSSASCA, we perform a series of experiments using different numbers of VMs and physical machines. The results of MOSSASCA are compared with well-known methods, including the nondominated sorting genetic algorithm (NSGA-II), multiobjective particle swarm optimization (MOPSO), a multiobjective evolutionary algorithm with decomposition (MOEAD), and a multiobjective sine-cosine algorithm (MOSCA). The results reveal that MOSSASCA outperforms the compared methods in terms of solving MOP problems and achieving the three objectives. Compared with the other methods, MOSSASCA exhibits a better ability to reduce power consumption and SLAVs while increasing MTBHS. The main differences in terms of power consumption between the MOSCA, MOPSO, MOEAD, and NSGA-II and the MOSSASCA are 0.53, 1.31, 1.36, and 1.44, respectively. Additionally, the MOSSASCA has higher MTBHS value than MOSCA, MOPSO, MOEAD, and NSGA-II by 362.49, 274.70, 585.73 and 672.94, respectively, and the proposed method has lower SLAV values than MOPSO, MOEAD, and NSGA-II by 0.41, 0.28, and 1.27, respectively.
The corporate headquarters in organization design theory: an organizational economics perspective
Authors: Foss Nicolai J. 
Published: April 2019

AbstractThe corporate headquarters (CHQ) is an important part of the organization of large firms; yet, it is neglected in organization design theory. In this brief essay, I argue that we need a better understanding of the CHQ to further our understanding of the link between the top-management team and the rest of the organization, and to improve our understanding of the costs and benefits of hierarchical organization in general. I outline a number of organizational economics ideas that may help addressing these challenges.
Expanded Analysis of Secondary Germline Findings From Matched Tumor/Normal Sequencing Identifies Additional Clinically Significant Mutations
Authors: Ileana Dumbrava Ecaterina , Brusco Lauren , Daniels Molly S. , Wathoo Chetna , Shaw Kenna R. , Lu Karen H. , Zheng Xiaofeng , Strong Louise C. , Litton Jennifer , Arun Banu K. , Eterovic A. Karina , Routbort Mark J. , Patel Keyur P. , Qi Yuan , Piha-Paul Sarina A. , Subbiah Vivek , Hong David S. , Rodon Jordi , Kopetz Scott , Mendelsohn John , Mills Gordon B. , Chen Ken , Meric-Bernstam Funda 
Published: April 2019

Purpose Next-generation sequencing (NGS) for tumor molecular profiling can reveal secondary germline likely pathogenic and pathogenic variants (LPV/PV). The American College of Medical Genetics and Genomics (ACMG) recommends return of secondary results for a subset of 59 genes, but other genes with evidence of clinical utility are emerging. We previously reported that 4.3% of patients who underwent NGS of a targeted panel of 201 genes had LPV/PV on the basis of the ACMG list. We report the frequency of additional germline cancer-related gene variants and discuss their clinical utility. Patients and Methods Matched tumor and germline DNA NGS of a targeted panel of 201 genes was performed in a research laboratory on samples from 1,000 patients with advanced or metastatic solid tumors enrolled in a molecular testing protocol ( ClinicalTrials.gov identifier: NCT01772771). The frequency of germline LPV/PV in 54 cancer-related genes, beyond the genes in ACMG list, were analyzed. Results Among 1,000 patients who underwent tumor/normal DNA sequencing, 46 (4.6%) were found to have a germline LPV/PV in the following genes: AR (n = 5), ATM (n = 4), BAP1 (n = 1), CDH1 (n = 1), CDKN2A (n = 1), CHEK1 (n = 2), CHEK2 (n = 10), EGFR (n = 1), ERCC3 (n = 4), ERCC5 (n = 1), HNF1B (n = 1), HRAS (n = 1), MITF (n = 4), MLL3 (n = 1), NF1 (n = 3), PKHD1 (n = 4), PTCH1 (n = 1), and SMARCA4 (n = 1). Thus, 8.7% of patients had an LPV/PV, with two patients having two concomitant germline LPV/PV. Five mutations in high-penetrance hereditary cancer predisposition genes were selected to be returned to patients or their representatives: BAP1, CDH1, CDKN2A, EGFR, and SMARCA4. Conclusion Broader genomic testing is likely to identify additional secondary pathogenic germline alterations, some with potential clinical utility for return to patients and their relatives. The recommended genes for which germline results should be returned are continually changing, which warrants continued study.
The fate of cells undergoing spontaneous DNA damage during development
Authors: Miermont Agnes , Antolović Vlatka , Lenn Tchern , Nichols John M. E. , Millward Lindsey J. , Chubb Jonathan R. 
Published: April 2019

ABSTRACT
Embryonic development involves extensive and often rapid cell proliferation. An unavoidable side effect of cell proliferation is DNA damage. The consequences of spontaneous DNA damage during development are not clear. Here, we define an approach to determine the effects of DNA damage on cell fate choice. Using single cell transcriptomics, we identified a subpopulation of Dictyostelium cells experiencing spontaneous DNA damage. Damaged cells displayed high expression of rad51, with the gene induced by multiple types of genotoxic stress. Using live imaging, we tracked high Rad51 cells from differentiation onset until cell fate assignment. High Rad51 cells were shed from multicellular structures, excluding damaged cells from the spore population. Cell shedding resulted from impaired cell motility and defective cell-cell adhesion, with damaged cells additionally defective in activation of spore gene expression. These data indicate DNA damage is not insulated from other aspects of cell physiology during development and multiple features of damaged cells prevent propagation of genetic error. Our approach is generally applicable for monitoring rare subpopulations during development, and permits analysis of developmental perturbations occurring within a physiological dynamic range.