bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transoral robotic surgery for oropharyngeal squamous cell carcinoma in the era of human papillomavirus
Authors: Mahmoud Omar , Sung Kim , Civantos Francisco J. , Thomas Giovanna R. , Samuels Michael A. 
Published: December 2017

AbstractBackgroundThe emergence of transoral robotic surgery (TORS) ignited the debate between surgical and nonsurgical strategies on oropharyngeal squamous cell carcinoma (SCC) management; a question further complicated by human papillomavirus (HPV). We evaluated the survival by treatment strategy independently in HPV‐related and HPV‐nonrelated oropharyngeal SCC.MethodsThe National Cancer Database was queried for patients with oropharyngeal SCC with known HPV status who underwent primary TORS or primary radiotherapy. The overall survival (OS) was compared by treatment strategy, including propensity matching to control for confounders.ResultsOf 1873 patients, 73% were HPV‐positive and 30% were treated with TORS. The propensity‐matched patients with HPV‐positive disease displayed no significant difference in 3‐year survival; 95% versus 91% (P = .116) for the TORS versus primary radiotherapy. In the HPV‐negative cohort, TORS was associated with superior survival; 84% versus 66% (P = .01).ConclusionThe TORS‐based approach was associated with superior survival in patients with HPV‐negative oropharyngeal SCC; similar difference was not observed in patients with HPV‐positive disease.
American Thyroid Association ultrasound system for the initial assessment of thyroid nodules: Use in stratifying the risk of malignancy of indeterminate lesions
Authors: Trimboli Pierpaolo , Deandrea Maurilio , Mormile Alberto , Ceriani Luca , Garino Francesca , Limone Paolo P. , Giovanella Luca 
Published: December 2017

AbstractBackgroundThe ultrasound risk stratification system of the American Thyroid Association (ATA) is frequently adopted in clinical practice. Here, we evaluated its performance in a series of nodules with indeterminate fine‐needle aspiration cytology (FNAC) report.MethodsIndeterminate thyroid nodules diagnosed at 2 medical centers were retrospectively screened, ultrasound images were reevaluated, and lesions were classified according to the ATA. Single ultrasound parameters were also analyzed.ResultsOne hundred seventy‐three indeterminate lesions were included with 24.8% of malignancy. The high suspicion class showed a cancer rate (75%) significantly (P < .001) higher than that recorded in the other categories (16.8%). Between ultrasound parameters, halo and microcalcifications were the most sensitive and specific ones. The most accurate receiver operating characteristic (ROC)‐derived cutoff of nodule's diameter was >4.1 cm. At multivariate analysis, only the ATA class of high suspicion and size >4.1 cm were significantly associated with cancer (odds ratios [ORs] 19.4 and 5.4, respectively).ConclusionThe ATA ultrasound system is reliable in the risk stratification of indeterminate thyroid lesions.
In vitro toxicity assessment of nanocrystals in tissue‐type cells and macrophage cells
Authors: Chen Meiling , Li Ying , Zhou Jiezhao , Yang Zhenbo , Wang Zhiyuan , Yang Yang , Zhang Hui , Li Zhiping , Mei Xingguo 
Published: December 2017

AbstractNanocrystals (NCs), a type of innovative material particle, are a potential drug delivery platform that aims to improve the bioavailability of hydrophobic drugs. However, due to the lack of consideration of their toxicity, existing studies have not investigated whether the nanoscale properties of NCs, such as particle sizes, may lead to NC‐induced toxicity. Because of the disparity between the rapid development of NCs and the lack of studies regarding NC toxicity, the present study investigated possible NC toxicity and clarified the relationship between particle sizes and NC toxicity. RAW264.7 and HepG2 cells were chosen as representatives of macrophage cells and tissue‐type cells, respectively. Monosodium urate NCs were used as a drug model. Different particle sizes of monosodium urate NCs were prepared using precipitation methods. Methyl tetrazolium, lactate dehydrogenase, oxidative stress and apoptosis/necrosis assays were then used to evaluate cell damage and recovery. The results showed that small NC particle sizes produced higher toxicity than larger ones. In immune cells, these cytotoxic effects were greater than in tissue cells. After removal of small NCs, tissue cell damage could be significantly reversed, while immune cells were only slightly restored. However, after removal of large NCs, both cell types had almost no recovery. In summary, despite conventional wisdom, our research confirmed that NCs are not very safe and that NC particle sizes are closely related to the degree of NC toxicity.
Intra‐articular injection of autologous adipose‐derived mesenchymal stem cells in the treatment of knee osteoarthritis
Authors: Spasovski Duško , Spasovski Vesna , Baščarević Zoran , Stojiljković Maja , Vreća Miša , Anđelković Marina , Pavlović Sonja 
Published: December 2017

AbstractBackgroundOsteoarthritis (OA) is a chronic degenerative joint disease and is considered to be the fourth leading cause of disability and the second cause of inability to work in men. Recently, adipose‐derived mesenchymal stem cells (AD‐MSCs) came into focus for regenerative medicine as a promising tool for the treatment of OA. The administration of stem cells into impaired joints results in pain relief and improves quality of life, accompanied by restoration of hyaline articular cartilage.MethodsIn the present study, nine patients (including two patients with bilateral symptoms) diagnosed with osteoarthritis (International Knee Documentation grade B in 5 and grade D in six knees) were treated using a single injection of AD‐MSCs at a concentration of 0.5–1.0 × 107 cells and were followed up for 18 months. During follow‐up, all the cases were evaluated clinically by Knee Society score (KSS), Hospital for Special Surgery knee score (HSS‐KS), Tegner–Lysholm (T–L) score and visual analogue scale (VAS) of pain, as well as by plain radiography and by magnetic resonance imaging visualization with 2D Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score assessment.ResultsSignificant improvement of all four clinical scores was observed within the first 6 months (KSS for 41.4 points, HSS‐KS for 33.9 points, T–L score for 44.8 points, VAS of pain from 54.5 to 9.3) and improvement persisted throughout the rest of the follow‐up. MOCART score showed significant cartilage restoration (from 43 ± 7.2 to 63 ± 17.1), whereas radiography showed neither improvement, nor further joint degeneration.ConclusionsThe results obtained in the present study provide good basis for prospective randomized controlled clinical trials with respect to the use of AD‐MSCs in the treatment of osteoarthritis.
Enhanced phosphorylation of sphingosine and ceramide sustains the exuberant proliferation of endothelial progenitors in Kaposi sarcoma
Authors: Abdel Hadi Loubna , Calcaterra Francesca , Brambilla Lucia , Carenza Claudia , Marfia Giovanni , Della Bella Silvia , Riboni Laura 
Published: December 2017

Abstract
Endothelial colony-forming cells (ECFCs), a unique endothelial stem cell population, are highly increased in the blood of Kaposi sarcoma (KS) patients. KS-derived ECFCs (KS-ECFCs) are also endowed with increased proliferative and vasculogenic potential, thus suggesting that they may be precursors of KS spindle cells. However, the mechanisms underlying the increased proliferative activity of KS-ECFCs remain poorly understood. Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) are metabolically interconnected sphingoid mediators crucial to cell proliferation. Here, we investigated the metabolism, release, and proliferative effects of S1P and C1P in KS-ECFCs compared with control ECFCs (Ct-ECFCs). Metabolic studies by cell labeling, chromatographic analyses, and digital autoradiography revealed that S1P and C1P biosynthesis and S1P secretion are all efficient processes in KS-ECFCs, more efficient in KS-ECFCs than Ct-ECFCs. Quantitative PCR analyses demonstrated a significantly higher ceramide kinase and sphingosine kinase-2 expression in KS-ECFCs. Notably, also the expression of S1P1 and S1P3 receptors was augmented in KS-ECFCs. Accordingly, treatment with exogenous C1P or S1P induced a significant, concentration-dependent stimulation of KS-ECFC proliferation, but was almost completely ineffective in Ct-ECFCs. Hence, we identified C1P and S1P as autocrine/paracrine proliferative signals in KS-ECFCs. A better understanding of the mechanisms that enhance S1P/C1P formation in KS-ECFCs may yield effective therapeutic modalities.
Functional divergence and comparative in‐silico study of Cas4 proteins of DUF83 class
Authors: Kaushik Vineeta , Verma Ved Vrat , Goel Manisha 
Published: December 2017

AbstractClustered Regularly Interspaced Short Palindromic Repeats‐CRISPR associated (CRISPR‐Cas) systems present in genomes of bacteria and archaea have been the focus of many research studies recently. The Cas4 proteins of these systems are thought to be responsible for the adaptation step in the CRISPR mechanism. Cas4 proteins exhibit low sequence similarity among themselves and are currently classified into 2 main classes: DUF83 and DUF911. The characteristic features of Cas4 proteins belonging to DUF83 class have been elucidated by determining the structures of Cas4 protein from Sulfolobus solfataricus and Pyrobaculum calidifontis. Although, both Cas4 proteins characterized structurally are of same DUF83 class, these 2 proteins do exhibit significant biochemical and functional differences. The aim of the present study was to explore the structural and evolutionary features responsible for these differences. Our study predicts residues which might be responsible for such differences. Functional divergence analysis was used to predict sites exhibiting type I divergence, where certain amino acids are conserved in 1 clade whereas the same site is highly variable in the other clade. Our intra‐molecular interaction analysis reinforces the influence of such divergence sites on the other functionally important amino acids. In general, this study identifies some of the divergence hotspots that could be the focus of future experimental studies for better understanding of Cas4 enzymatic activity in CRISPR mechanism.
Posttraumatic Stress Symptoms and Posttraumatic Growth in Children and Adolescents Following an Earthquake: A Latent Transition Analysis
Authors: Chen Jieling , Wu Xinchun 
Published: December 2017

AbstractThis study examined the transitions in classes of posttraumatic stress symptoms and posttraumatic growth in a sample of children and adolescents (N = 757), between 8 and 20 months after the 2013 Ya'an earthquake in China. Using latent profile analysis, three classes of symptoms (resilient, thriving, and struggling) were identified at 8 and 20 months after the earthquake. Latent transition analysis indicated that the majority of survivors remained in the same class during the period, while others showed a transition between different classes over time. The transition was mainly characterized by three paths: from struggling to resilient, and from thriving to either resilient or struggling. Of the survivors who were classified as thriving at 8 months, those transitioning to the struggling class at 20 months were more likely to experience higher levels of loss and injury compared with those transitioning to the resilient class (Cohen's d = 0.72) or remaining in the thriving class (Cohen's d = 0.36) at 20 months postearthquake. Survivors who remained stable in the struggling class were older than those who remained stable in the thriving class (Cohen's d = 0.41) or those who moved from thriving at 8 months to resilient at 20 months after the earthquake (Cohen's d = 0.39). It is recommended that clinicians consider the classes of posttraumatic stress symptoms and posttraumatic growth, and the potential development paths and associated factors, when implementing interventions for children and adolescents after a natural disaster.
Quality indicators of oropharyngeal cancer care in the elderly
Authors: Gourin Christine G. , Herbert Robert J. , Fakhry Carole , Quon Harry , Kang Hyunseok , Kiess Ana P. , Koch Wayne M. , Eisele David W. , Frick Kevin D. 
Published: December 2017

ObjectiveTo examine associations between quality of care, survival, and costs in elderly patients treated for oropharyngeal squamous cell cancer (OPSCC).Study DesignRetrospective analysis of Surveillance, Epidemiology, and End Results‐Medicare data.MethodsWe evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using multivariate regression and survival analysis. Using quality indicators derived from guidelines for recommended care, summary measures of quality were calculated for diagnosis, initial treatment, surveillance, treatment for recurrence, end‐of‐life care, performance, and an overall summary measure of quality.ResultsHigher‐quality care was associated with significant differences in survival for initial treatment (hazard ratio [HR] = 0.55 [0.41 to 0.73]), surveillance (HR = 0.32 [0.22 to 0.48]), treatment of recurrence (HR = 2.37 [1.56 to 3.60]), performance measures (HR = 0.50 [0.36 to 0.69]), and the overall summary measure of quality (HR = 0.53 [0.39 to 0.71]). Higher‐quality salvage surgery was associated with improved survival (HR = 0.16 [0.04 to 0.54]), whereas higher‐quality chemotherapy given for recurrence was associated with worse survival (HR = 5.70 [1.92 to 16.94]). Overall, higher‐quality care was not associated with differences in costs. Higher‐quality care was associated with significantly lower mean incremental costs for treatment of recurrence and end‐of‐life care, and higher costs for diagnosis and surveillance.ConclusionHigher‐quality OPSCC care in elderly patients was associated with improved survival; however, higher‐quality care was not associated with reduced costs, and higher‐quality care for treatment of recurrence was associated with poorer survival, primarily due to poorer survival in patients treated with palliative chemotherapy. These data demonstrate a complex relationship between quality and costs in elderly OPSCC patients, which can be used to frame discussions of value and guide disease‐specific quality‐measure development.Level of Evidence2c. Laryngoscope, 128:2312–2319, 2018
Health‐related quality of life and economic burden of vestibular loss in older adults
Authors: Agrawal Yuri , Pineault Kevin G. , Semenov Yevgeniy R. 
Published: December 2017

ObjectivesVestibular loss is a debilitating condition, and despite its high prevalence in older adults, the quality of life (QoL) burden of vestibular loss in older individuals has not been well‐studied. This report quantifies the impact on overall QoL and identifies domains of health most affected. We hypothesize vestibular loss will be associated with impairment in diverse domains of health‐related QoL.Study DesignProspective, case‐control study.MethodsA convenience sample of 27 patients age ≥60 years with vestibular physiologic loss was recruited from an academic neurotology clinic. The patients did not have any identifiable cause of their vestibular loss other than aging. The convenience sample was compared to an age‐matched cross‐sectional sample of the general US population (n = 1266). The main outcome was QoL measured by the Ontario Health Utilities Index Mark III (HUI3).ResultsCompared to the general population, patients with vestibular loss had significantly lower overall unadjusted HUI3 scores (−0.32, p < 0.001). Multivariate regression analysis showed vestibular loss was significantly associated with poorer performance in vision (−0.11 p < 0.0001), speech (−0.15, p < 0.0001), dexterity (−0.13, p < 0.0001), and emotion (−0.07, p = 0.0065). Adjusted aggregate HUI3 was also significantly lower for vestibular loss (−0.15, p = 0.0105). These QoL decrements resulted in an average loss of 1.30 Quality‐Adjusted Life Years (QALYs). When using a $50,000/QALY willingness‐to‐pay threshold, vestibular loss was associated with a $64,929 lifetime economic burden per affected older adult, resulting in a total lifetime societal burden of $227 billion for the US population ≥60 years of age.ConclusionsLoss of vestibular function with aging significantly decreases quality of life across multiple domains of well‐being. These QoL reductions are responsible for heavy societal economic burdens of vestibular loss, which reveal potential benefits of prompt diagnosis and treatment of this condition.Level of Evidence3
Nrf2 promotes oesophageal cancer cell proliferation via metabolic reprogramming and detoxification of reactive oxygen species
Authors: Kitano Yuki , Baba Yoshifumi , Nakagawa Shigeki , Miyake Keisuke , Iwatsuki Masaaki , Ishimoto Takatsugu , Yamashita Yo‐ichi , Yoshida Naoya , Watanabe Masayuki , Nakao Mitsuyoshi , Baba Hideo 
Published: December 2017

AbstractCancer cells consume a large amount of energy and maintain high levels of anabolism to promote cell proliferation via metabolic reprogramming. Nuclear factor erythroid 2‐related factor 2 (Nrf2; NFE2L2) is a master transcription regulator of stress responses and promotes metabolic reprogramming to support cell proliferation in various types of cancer. As oesophageal cancer is one of the most aggressive gastrointestinal cancers, we aimed to clarify the effect of Nrf2 on metabolic reprogramming in oesophageal cancer. The relationship between Nrf2 expression and clinical outcome was evaluated using a database comprising 201 oesophageal cancers. Using in vitro assays and metabolome analysis, we examined the mechanism by which Nrf2 affects malignant phenotype. High‐level immunohistochemical expression of Nrf2 was significantly associated with poor recurrence‐free survival (HR = 2.67, p = 0.0004) and overall survival (HR = 2.90, p < 0.0001) in oesophageal cancer patients. In an in vitro assay with siRNA in TE‐11 cells, which showed high Nrf2 expression, Nrf2 depletion significantly decreased cell growth and enhanced G1 cell cycle arrest and apoptosis. In addition, reactive oxygen species (ROS) were not removed by detoxification via the Nrf2 pathway, with concomitant induction of the p38 mitogen‐activated protein kinase pathway. The metabolome analysis showed that Nrf2 strongly promoted metabolic reprogramming to glutathione metabolism, which synthesizes the essential fuels for cancer progression. Furthermore, metabolome analysis using oesophageal cancer specimens confirmed that samples displaying high Nrf2 expression promoted glutathione synthesis. Metabolic reprogramming to glutathione metabolism, and ROS detoxification by activation of Nrf2, enhanced cancer progression and led to a poor clinical outcome in oesophageal cancer patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Morphological reorganization and mechanical enhancement in multilayered polyethylene/polypropylene films by layer multiplication or mild annealing
Authors: Mauri Michele , Ponting Michael , Causin Valerio , Simonutti Roberto , Pisciotti Francesco 
Published: December 2017

ABSTRACTShortly after processing, Polyethylene/Polypropylene (PE/PP) multilayer films demonstrate an increase in tensile modulus and other mechanical properties when the individual layer thickness is below 0.5 µm. Subsequent annealing at 60 °C for 16 h brings the properties of all other samples to similar values. WAXD characterization of the layered films identified a prevalence of mesophase in the thicker PP layers. In samples with increased layer numerosity or subjected to annealing, WAXD detected its conversion to α crystalline phase that correlates with improved mechanical properties. SSNMR and DSC detailed the defective nature of α iPP crystallites. Comonomers, detected by NMR in the commercial polymers used for the films, are the source of “tunable disorder” that dictates the formation of the PP mesophase and the low temperature of conversion to the mechanically stronger defective α phase. Soft intrafilm layer interfaces instead enable nucleation and localized polymer chain rearrangement even without annealing. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 520–531
Secondary structure of cell‐penetrating peptides during interaction with fungal cells
Authors: Gong Zifan , Ikonomova Svetlana P. , Karlsson Amy J. 
Published: December 2017

AbstractCell‐penetrating peptides (CPPs) are peptides that cross cell membranes, either alone or while carrying molecular cargo. Although their interactions with mammalian cells have been widely studied, much less is known about their interactions with fungal cells, particularly at the biophysical level. We analyzed the interactions of seven CPPs (penetratin, Pep‐1, MPG, pVEC, TP‐10, MAP, and cecropin B) with the fungal pathogen Candida albicans using experiments and molecular simulations. Circular dichroism (CD) of the peptides revealed a structural transition from a random coil or weak helix to an α‐helix occurs for all peptides when the solvent is changed from aqueous to hydrophobic. However, CD performed in the presence of C. albicans cells showed that proximity to the cell membrane is not necessarily sufficient to induce this structural transition, as penetratin, Pep‐1, and MPG did not display a structural shift in the presence of cells. Monte Carlo simulations were performed to further probe the molecular‐level interaction with the cell membrane, and these simulations suggested that pVEC, TP‐10, MAP, and cecropin B strongly penetrate into the hydrophobic domain of the membrane lipid bilayer, inducing a transition to an α‐helical conformation. In contrast, penetratin, Pep‐1 and MPG remained in the hydrophilic region without a shift in conformation. The experimental data and MC simulations combine to explain how peptide structure affects their interaction with cells and their mechanism of translocation into cells (direct translocation vs. endocytosis). Our work also highlights the utility of combining biophysical experiments, biological experiments, and molecular modeling to understand biological phenomena.