bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma
Authors: de Vicente Juan C. , Rodríguez-Santamarta Tania , Rodrigo Juan P. , Blanco-Lorenzo Verónica , Allonca Eva , García-Pedrero Juana M. 
Published: November 2018

Abstract

Background:
The immune checkpoint PD-1 and its ligand PD-L1 are involved in the induction of immunological tolerance of solid tumors including oral squamous cell carcinoma (OSCC). The aim of the study was to establish the clinical and prognostic significance of PD-L1 in OSCC.

Methods:
Tissue microarrays of 125 resected OSCC were stained with two different commercially available PD-L1 antibodies (clones E1L3N and 22C3), alongside PD-1 immunostaining.

Results:
PD-L1 expression in more than 10% of tumor cells was associated with poorer survival, and established as a clinically relevant cut-off point. This relevant PD-L1 expression was detected in 10% to 15% OSCC specimens depending on the anti-PD-L1 antibody, and showed an inverse correlation with tobacco and alcohol consumption. We consistently found that PD-L1 expression was associated with tumor recurrence and lower disease-specific survival. Multivariate analysis further revealed that neck node metastasis (HR 2.304; P = 0.009) and tumor PD-L1 expression (HR 2.571; P = 0.01) were significant independent factors for poor prognosis.

Conclusions:
PD-L1 expression in more than 10% of tumor cells was a significant and independent factor of poor prognosis in OSCC.

Impact:
PD-L1 expression in more than 10% of tumor cells was consistently established as a clinically relevant cut-off point by using two different antibodies. Remarkably, PD-L1 expression emerges as an independent poor prognosis marker in patients with OSCC.
Internalization of Exosomes through Receptor-Mediated Endocytosis
Authors: Gonda Amber , Kabagwira Janviere , Senthil Girish N. , Wall Nathan R. 
Published: November 2018

AbstractThe tumor microenvironment is replete with factors secreted and internalized by surrounding cells. Exosomes are nano-sized, protein-embedded, membrane-bound vesicles that are released in greater quantities from cancer than normal cells and taken up by a variety of cell types. These vesicles contain proteins and genetic material from the cell of origin and in the case of tumor-derived exosomes, oncoproteins and oncogenes. With increasing understanding of the role exosomes play in basic biology, a more clear view of the potential exosomes are seen to have in cancer therapeutics emerges. However, certain essential aspects of exosome function, such as the uptake mechanisms, are still unknown. Various methods of cell–exosome interaction have been proposed, but this review focuses on the protein–protein interactions that facilitate receptor-mediated endocytosis, a broadly used mechanism by a variety of cells.
Towards the Quantification of Peggy Babcock: Speech Errors and Their Position within the Word
Authors: Mooshammer Christine , Tiede Mark , Shattuck-Hufnagel Stefanie , Goldstein Louis 
Published: November 2018

Abstract
Sequences of similar (i.e., partially identical) words can be hard to say, as indicated by error frequencies, longer reaction and execution times. This study investigates the role of the location of this partial identity and the accompanying differences, i.e. whether errors are more frequent with mismatches in word onsets (top cop), codas (top tock) or both (pop tot). Number of syllables (tippy ticky) and empty positions (top ta) were also varied. Since the gradient nature of errors can be difficult to determine acoustically, articulatory data were investigated. Articulator movements were recorded using electromagnetic articulography, for up to 9 speakers of American English repeatedly producing 2-word sequences to an accelerating metronome. Most word pairs showed more intrusions and greater variability in coda than in onset position, in contrast to the predominance of onset position errors in corpora from perceptual observation.
Intensive Statin Therapy for Acute Ischemic Stroke to Reduce the Number of Microemboli: A Preliminary, Randomized Controlled Study
Authors: Chen Xingyu , Zhuang Xiaorong , Peng Zhongwei , Yang Huili , Chen Liangyi , Yang Qingwei 
Published: November 2018

<b><i>Background:</i></b> To assess whether intensive statin therapy reduces the occurrence of microemboli in patients with acute ischemic stroke. <b><i>Methods:</i></b> Patients with acute ischemic stroke within 72 h of onset were randomized to the intensive statin (atorvastatin 60 mg/day, adjusted to 20 mg/day after 7 days) and control (atorvastatin 20 mg/day) groups. Combined aspirin and clopidogrel were used for antiplatelet therapy. Microemboli were monitored by transcranial Doppler on days 1 (pre-treatment), 3, and 7. Metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hs-CRP), and National Institutes of Health Stroke Scale (NIHSS) score were assessed on days 1 and 7. The modified Rankin scale (mRS) was used on day 90. The primary outcome was the proportion of patients with microemboli on day 3. <b><i>Results:</i></b> There were 35 (58.3%) and 30 (52.6%) patients with microemboli in the intensive statin (<i>n</i> = 60) and control (<i>n</i> = 57) groups, respectively, on day 1 (<i>p</i> = 0.342). On day 3, there were significantly less microemboli in the intensive statin group (<i>n</i> = 9; 15.0%) compared with controls (<i>n</i> = 16; 28.1%; <i>p</i> = 0.002). No difference was observed in MMP-9 and hs-CRP levels on day 1, but on day 7, MMP-9 (median 79.3 vs. 95.9 μg/L; <i>p</i> = 0.004) and hs-CRP (median 2.01 vs. 3.60 mg/L; <i>p</i> = 0.020) levels were lower in the intensive statin group compared with controls. There were no differences in NIHSS scores on days 1 and 7. There was no difference in mRS on day 90. <b><i>Conclusion:</i></b> Intensive atorvastatin therapy in patients with acute ischemic stroke reduces the occurrence of microemboli and inflammation, with no overt adverse events.
Do Out‐of‐Hospital Cardiac Arrest Patients Have Increased Chances of Survival When Transported to a Cardiac Resuscitation Center?
Authors: Lipe Demis , Giwa Al , Caputo Nicholas D. , Gupta Nachiketa , Addison Joseph , Cournoyer Alexis 
Published: November 2018

Background
Patients suffering from an out‐of‐hospital cardiac arrest are often transported to the closest hospital. Although it has been suggested that these patients be transported to cardiac resuscitation centers, few jurisdictions have acted on this recommendation. To better evaluate the evidence on this subject, a systematic review and meta‐analysis of the currently available literature evaluating the association between the destination hospital's capability (cardiac resuscitation center or not) and resuscitation outcomes for adult patients suffering from an out‐of‐hospital cardiac arrest was performed.

Methods and Results

PubMed,
EMBASE
, and the Cochrane Library databases were first searched using a specifically designed search strategy. Both original randomized controlled trials and observational studies were considered for inclusion. Cardiac resuscitation centers were defined as having on‐site percutaneous coronary intervention and targeted temperature management capability at all times. The primary outcome measure was survival. Twelve nonrandomized observational studies were retained in this review. A total of 61 240 patients were included in the 10 studies that could be included in the meta‐analysis regarding the survival outcome. Being transported to a cardiac resuscitation center was associated with an increase in survival (odds ratio=1.95 [95% confidence interval 1.47‐2.59],
P
<0.001).

Conclusions

Adult patients suffering from an out‐of‐hospital cardiac arrest transported to cardiac resuscitation centers have better outcomes than their counterparts. When possible, it is reasonable to transport these patients directly to cardiac resuscitation centers (class
II
a, level of evidence B, nonrandomized).

Clinical Trial Registration

URL
:
www.crd.york.ac.uk/PROSPERO/
. Unique identifier:
CRD
42018086608.
The Microbiology of Complicated Acute Sinusitis among Pediatric Patients: A Case Series
Authors: Mulvey Carolyn L. , Kiell Eleanor P. , Rizzi Mark D. , Buzi Adva 
Published: November 2018

ObjectiveThe microbiology of pediatric complicated acute rhinosinusitis (ARS) has evolved, and our current understanding of pathogenic organisms is limited. The objectives of this study are to describe the incidence of pathogens causing complicated ARS requiring surgical intervention at our institution over a 10‐year period as well as their associated treatment outcomes.Study DesignRetrospective cohort study.SettingA single tertiary care children's hospital.Subjects and MethodsData were reviewed from all patients who underwent surgery for complicated ARS and had positive culture data from 2006 to 2016. Associations among pathogens, complications, and outcomes were analyzed with Pearson χ2 and Wilcoxon rank‐sum tests.ResultsEighty‐nine patients met criteria. Complications included orbital infections (78%), intracranial infections (48%), Pott's puffy tumor (13%), and cavernous sinus thrombosis (9.0%). Bacterial isolates were majority polymicrobial (55%) and included Streptococcus species (58%), Staphylococcus species (49%; including methicillin‐resistant S aureus [MRSA], 11%), and anaerobic bacteria (35%). S pneumoniae (9.0%), Haemophilus species (4.5%), and Moraxella catarrhalis (1.1%) were relatively uncommon. Bacterial isolates were similar among patients with all types of complications.ConclusionAmong a large cohort of pediatric patients with complicated ARS, most bacterial isolates were polymicrobial, with Streptococcus and Staphylococcus species contributing to the majority of cases. S aureus species, including MRSA and anaerobic pathogens, were common. The pattern of bacterial isolates was similar among patients with all types of complications of ARS. We suggest treatment for complicated ARS with broad‐spectrum antibiotics with coverage for Streptococcus species, Staphylococcus species including MRSA, and anaerobic bacteria.
The Rotator Cuff Healing Index: A New Scoring System to Predict Rotator Cuff Healing After Surgical Repair
Authors: Kwon Jieun , Kim Sae Hoon , Lee Ye Hyun , Kim Tae In , Oh Joo Han 
Published: November 2018

Background: Scoring systems integrating possible prognostic factors and predicting rotator cuff healing after surgical repair could provide valuable information for clinical practice. Purpose: To determine the prognostic factors predictive of rotator cuff healing after surgical repair and to integrate these factors into a scoring system. Study Design: Case-control study; Level of evidence, 3. Methods: The authors reviewed the records of 603 patients who, at least 12 months after primary rotator cuff repair by a single surgeon, had magnetic resonance imaging or computed tomographic arthrography to assess repair integrity. The mean age at the time of surgery was 60 years (range, 39-81 years), and 378 patients were women (62.7%). Previous known or suggested factors affecting cuff integrity were analyzed through univariate and multivariate analyses. Factors identified in the multivariate analysis were integrated in a scoring system based on odds ratios (ORs). Results: The overall healing failure rate was 24%. The following independent risk factors were identified in the multivariate analysis: age >70 years at the time of surgery ( P = .003, OR = 2.71), size of the tear in anteroposterior dimension ( P = .033, OR = 1.94) and retraction ( P = .000, OR = 4.56), fatty infiltration of infraspinatus exceeding grade 2 ( P = .001, OR = 2.91), low bone mineral density (T score ≤ –2.5, P = .04, OR = 1.95), and high level of work activity ( P = .036, OR = 2.18). A 15-point scoring system comprised the following: 4 points for retraction; 3 points for fatty infiltration of infraspinatus; and 2 points for anteroposterior tear size, age, bone mineral density, and work activity, weighted according to multivariate analysis ORs. Patients with ≤4 points had a 6.0% healing failure rate, and those with ≥5 and ≥10 points had 55.2% and 86.2% healing failure rates, respectively. Conclusion: A numerical scoring system including significant clinical and radiological factors was designed to predict healing of the rotator cuff after surgical repair. This scoring system helped predict the adequacy of the repair and assist in deciding the appropriate treatment options.
An Analysis of Protein Consumption in India Through Plant and Animal Sources
Authors: Rampal Priya 
Published: November 2018

Background: India became self-sufficient in food because of the Green Revolution in the 1960s. However, both the technological innovation and policy support have been biased toward cereals. It is expected that cereals are the major source of proteins in the diet. In recent years, the consumption of cereals is declining in spite of increasing output due to declining preference. Therefore, the country needs to increase production and consumption of pulses to meet the nutritional requirements of the population. Objectives: This article discusses the trends in pulse and protein consumption over the years. Further, it focuses on the substitutability and complementarity between various sources of proteins. Methods: A seemingly unrelated regression estimation (SURE) framework is used to study the price and income effect on proteins from different sources—cereals and pulses (plant sources), milk and milk products, animal sources such as eggs, fish, and meat, and other sources of protein. Results: It is found that the expenditure on proteins is large and significant. As income increases, consumption of proteins increases. Higher disposable incomes have led to higher demand of animal sources of proteins. There are significant food price effects in our analysis—negative for cereals and positive for eggs. As the price of pulses increases, consumption of animal sources of proteins increases. Conclusion: It becomes important to contain volatility in pulse prices given that it is a major source of plant protein. States distributing pulses in the Public Distribution System show higher consumption of proteins than other states.
Development of a simvastatin loaded injectable porous scaffold in situ formed by phase inversion method for bone tissue regeneration
Authors: Hajihasani Biouki Mina , Mobedi Hamid , Karkhaneh Akbar , Daliri Joupari Morteza 
Published: November 2018

Introduction: The use of injectable scaffolds as a minimally invasive method is a good choice in tissue engineering applications. A critical parameter for the tissue engineering scaffolds is a suitable morphology with interconnected pores. We present the development of a simvastatin loaded scaffold that forms in situ and provides the porous structure with interconnected pores. Methods: The formulation of these scaffolds includes a polymeric solution of poly lactic-co-glycolic acid (25 wt%) in N-methyl-2-pyrrolidone containing 6 wt% deionized water and porogen (mannitol, four times the weight of the polymer). We have grafted simvastatin to poly lactic-co-glycolic acid by the esterification reactions. Simvastatin or simvastatin-grafted poly lactic-co-glycolic acid in different levels was added to polymer solution and finally the solution was injected into phosphate buffered saline. The simvastatin-grafted poly lactic-co-glycolic acid was characterized by attenuated total reflection Fourier-transform infra-red and 1H-nuclear magnetic resonance spectroscopy. The morphology, porosity, and biocompatibility of the scaffolds were evaluated. The in vitro simvastatin release from the various formulations was studied. Osteogenic differentiation of the adipose-derived stem cells was investigated using alkaline phosphatase activity assay and cell mineralization was evaluated using Alizarin red staining. Results: The morphology results showed the resultant scaffold was porous with the interconnected pores. The scaffolds presented 91% porosity. Non-toxic doses of simvastatin in the scaffolds were determined by methyl-thiazolyl diphenyl-tetrazolium bromide assay. The released simvastatin from the scaffolds continues over 80 days. Alkaline phosphatase activity and Alizarin red results indicated that cell osteogenic differentiation is promoted. Conclusion: The results demonstrated that release of simvastatin from the injectable scaffolds can have positive effects on osteogenic differentiation of the adipose-derived stem cells.
Executive Insights: Roles of R&D and Manufacturing in Global Marketing Management
Authors: Bermingham John A. 
Published: November 2018

In today's world of global competition and high-speed product development, linkage among R&D, manufacturing, and marketing is more vital to successful business than ever before. Delivering a competitive product to the market at the right time, with the right specifications and feature benefits, all at a manufacturing cost that allows for profit, is one tough assignment. Add to this the global complexity of marketing, R&D, and manufacturing not being located in the same place, along with competing in an environment where world-class product development time is under 50 weeks, and you have a challenge that few companies are dealing with appropriately today. International marketing executives can no longer have the luxury of time to consider R&D and manufacturing as activities remotely related and remotely relevant to them. They have to deal with all of this complexity and be fully aware that without adequate understanding of the linkages necessary among marketing, R&D, and manufacturing, their businesses run a very high risk of failure ( Kotabe 1992 ). Based on my executive experience at three different companies, I have seen the same lingering problems. In this article, I will explore the essence of these problems and solutions based on my own experiences.
The Clinical Utility of Virtual Reality in Neurorehabilitation: A Systematic Review
Authors: Massetti Thais , da Silva Talita Dias , Crocetta Tânia Brusque , Guarnieri Regiani , de Freitas Bruna Leal , Bianchi Lopes Priscila , Watson Suzanna , Tonks James , de Mello Monteiro Carlos Bandeira 
Published: November 2018

Background: Virtual reality (VR) experiences (through games and virtual environments) are increasingly being used in physical, cognitive, and psychological interventions. However, the impact of VR as an approach to rehabilitation is not fully understood, and its advantages over traditional rehabilitation techniques are yet to be established. Method: We present a systematic review which was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). During February and March of 2018, we conducted searches on PubMed (Medline), Virtual Health Library Search Portal databases (BVS), Web of Science (WOS), and Embase for all VR-related publications in the past 4 years (2015, 2016, 2017, and 2018). The keywords used in the search were “neurorehabilitation” AND “Virtual Reality” AND “devices.” Results: We summarize the literature which highlights that a range of effective VR approaches are available. Studies identified were conducted with poststroke patients, patients with cerebral palsy, spinal cord injuries, and other pathologies. Healthy populations have been used in the development and testing of VR approaches meant to be used in the future by people with neurological disorders. A range of benefits were associated with VR interventions, including improvement in motor functions, greater community participation, and improved psychological and cognitive function. Conclusions: The results from this review provide support for the use of VR as part of a neurorehabilitation program in maximizing recovery.
Microarray analysis of long non-coding RNA and mRNA expression profiles in diabetic cardiomyopathy using human induced pluripotent stem cell–derived cardiomyocytes
Authors: Pant Tarun , Mishra Manoj K , Bai Xiaowen , Ge Zhi-Dong , Bosnjak Zeljko J , Dhanasekaran Anuradha 
Published: November 2018

Aim: This study aims to investigate the altered expression signature of long non-coding RNAs, mRNAs and deregulated pathways related to diabetic cardiomyopathy disease pathogenesis. Method: We utilize the previously established in vitro diabetic cardiomyopathy model of human induced pluripotent stem cell–derived human cardiomyocytes to perform long non-coding RNA and mRNA expression analysis on glucose (11 mM), endothelin-1 (10 nM) and cortisol (1 µM) stimulated human induced pluripotent stem cell–derived human cardiomyocytes to interrogate diabetic cardiomyopathy associated RNA expression profile. Result: Out of 20,730 mRNAs and 40,173 long non-coding RNAs being screened, 2046 long non-coding RNAs and 1582 mRNAs were differentially regulated (fold change > 2, p < 0.05) between diabetic cardiomyopathy and control group, of which more than half were intergenic and antisense long non-coding RNAs. Most of the coding transcripts were associated with processes like inflammation, structural reorganization, metabolism, smooth muscle contraction, focal adhesion and repair contributing towards the development of diabetic cardiomyopathy. The subgroup analysis further revealed 411 long non-coding RNAs being co-expressed with neighbouring genes. However, our coding–non-coding co-expression analysis showed an overall 48,155 co-expression network connections. In addition to that, the long non-coding RNAs with highest network connections were profoundly enriched for focal adhesion, cell-matrix adhesion and muscle contraction. Conclusion: These results provide comprehensive data about the pathways and regulatory mechanisms associated with diabetic cardiomyopathy and indicate that long non-coding RNAs may play a crucial role in diabetic cardiomyopathy.
Surface-based shared and distinct resting functional connectivity in attention-deficit hyperactivity disorder and autism spectrum disorder
Authors: Jung Minyoung , Tu Yiheng , Park Joel , Jorgenson Kristen , Lang Courtney , Song Wenwen , Kong Jian 
Published: November 2018

BackgroundBoth attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders with a high prevalence. They are often comorbid and both exhibit abnormalities in sustained attention, yet common and distinct neural patterns of ASD and ADHD remain unidentified.AimsTo investigate shared and distinct functional connectivity patterns in a relatively large sample of boys (7- to 15-year-olds) with ADHD, ASD and typical development matched by age, gender and IQ.MethodWe applied machine learning techniques to investigate patterns of surface-based brain resting-state connectivity in 86 boys with ASD, 83 boys with ADHD and 125 boys with typical development.ResultsWe observed increased functional connectivity within the limbic and somatomotor networks in boys with ASD compared with boys with typical development. We also observed increased functional connectivity within the limbic, visual, default mode, somatomotor, dorsal attention, frontoparietal and ventral attention networks in boys with ADHD compared with boys with ASD. In addition, using a machine learning approach, we were able to discriminate typical development from ASD, typical development from ADHD and ASD from ADHD with accuracy rates of 76.3%, 84.1%, and 79.3%, respectively.ConclusionsOur results may shed new light on the underlying mechanisms of ASD and ADHD and facilitate the development of new diagnostic methods for these disorders.Declaration of interestJ.K. holds equity in a startup company, MNT.