bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systemic insight into astrocytoma biology across different grades
Authors: Chakraborty Sohini , Ghosh Zhumur 
Published: August 2018

AbstractAstrocytomas are the most common type of brain tumors, which originate from glial cells, and are classified into specific grades based on their histopathological behavior. To develop precise therapeutic strategies for the disease, it is important to identify the molecular signatures specific to each grade as well as the key factors responsible for the transition from one grade to the next. In this study, we have taken a systems approach to investigate the gene expression profiles of each grades of the disease by mapping shortest paths of gene interaction in each grade and also between one grade and the next. Module core genes govern the topology of these networks and serve as important functional players in each grade as well as help in grade transition events. Shortlisted among these module core genes are well‐characterized players of glioma as well as novel molecules (32 grade‐specific genes and 15 grade transition–specific genes), which influence important prooncogenic functions but have not been linked to glioma biology yet. These module core genes provide interesting insight into the biology of astrocytic tumors and are potential therapeutic targets for astrocytoma.
Antrodia camphorata inhibits epithelial‐to‐mesenchymal transition by targeting multiple pathways in triple‐negative breast cancers
Authors: Hseu You‐Cheng , Chang Geng‐Ruei , Pan Jian‐You , Rajendran Peramaiyan , Mathew Dony Chacko , Li Mei‐Ling , Liao Jiunn‐Wang , Chen William Tzu‐Liang , Yang Hsin‐Ling 
Published: August 2018

AbstractAntrodia camphorata (AC) exhibits potential for engendering cell‐cycle arrest as well as prompting apoptosis and metastasis inhibition in triple‐negative breast cancer (TNBC) cells. We performed the current study to explore the anti‐epithelial‐to‐mesenchymal transition (EMT) properties of fermented AC broth in TNBC cells. Our results illustrated that noncytotoxic concentrations of AC (20–60 μg/ml) reversed the morphological changes (fibroblastic‐to‐epithelial phenotype) as well as the EMT by upregulating the observed E‐cadherin expression. Furthermore, we discovered treatment with AC substantially inhibit the Twist expression in human TNBC (MDA‐MB‐231) cells as well as in those that were transfected with Twist. In addition, we determined AC to decrease the observed Wnt/β‐catenin nuclear translocation through a pathway determined to be dependent on GSK3β. Notably, AC treatment consistently inhibited the EMT by downregulating mesenchymal marker proteins like N‐cadherin, vimentin, Snail, ZEB‐1, and fibronectin; at that same time upregulating epithelial marker proteins like occludin and ZO‐1. Bioluminescence imaging that was executed in vivo demonstrated AC substantially suppressed breast cancer metastasis to the lungs. Notably, we found that western blot analysis confirmed that AC decreased lung metastasis as demonstrated by upregulation of E‐cadherin expression in biopsied lung tissue. Together with our results support the anti‐EMT activity of AC, indicating AC as having the potential for acting as an anticancer agent for the treatment of human TNBC treatment.
Transcriptional regulation of CD4+ TH cells that mediate tissue inflammation
Authors: Loo Tiffany T , Gao Yuanyuan , Lazarevic Vanja 
Published: August 2018

Abstract
Acquired and genetic immunodeficiencies have revealed an indispensable role for CD4+ T cells in the induction of protective host immune responses against a myriad of microbial pathogens. Influenced by the cytokines present in the microenvironment, activated CD4+ T cells may differentiate into several highly-specialized helper subsets defined by the production of distinct signature cytokines tailored to combat diverse classes of pathogens. The process of specification and differentiation is controlled by networks of core, master, and accessory transcription factors, which ensure that CD4+ T helper (TH) cell responses mounted against an invading microbe are of the correct specificity and type. However, aberrant activation or inactivation of transcription factors can result in sustained and elevated expression of immune-related genes, leading to chronic activation of CD4+ TH cells and organ-specific autoimmunity. In this review, we provide an overview of the molecular basis of CD4+ TH cell differentiation and examine how combinatorial expression of transcription factors, which promotes genetic plasticity of CD4+ TH cells, can contribute to immunological dysfunction of CD4+ TH responses. We also discuss recent studies which highlight the potential of exploiting the genetic plasticity of CD4+ TH cells in the treatment of autoimmune and other immune-mediated disorders.
Review on how combinatorial expression of transcription factors, which promotes genetic plasticity of CD4+ TH cells, can contribute to immunological dysfunction of CD4+ TH responses.
Prolonged middle ear development in Rhinella horribilis
Authors: Womack Molly C. , Stynoski Jennifer L. , Voyles Meredith K. , Coloma Luis A. , Hoke Kim L. 
Published: August 2018

AbstractDespite the benefit of the tympanic middle ear to airborne hearing sensitivity, anurans range in how soon they develop functional middle ears after transitioning to life on land. Previous evidence suggested that bufonids had particularly slow middle ear developmental rates, but precise timelines have not yet been published for this family. Here, we provide the first age‐verified middle ear development timeline for a true toad species (family Bufonidae). We find that although middle ear development begins during metamorphosis in Rhinella horribilis, the middle ear remains incomplete 15 weeks after the transition from aquatic tadpole to land‐dwelling toadlet. Using this new middle ear timeline, we discuss commonalities and differences in middle ear development among bufonids, as well as among Anura.
The Impact of Resident and Fellow Participation in Transsphenoidal Pituitary Surgery
Authors: Wong Anni , Filimonov Andrey , Lee Yung‐Jae , Hsueh Wayne D. , Baredes Soly , Liu James K. , Eloy Jean Anderson 
Published: August 2018

Objectives/HypothesisPostoperative complications is an important marker of healthcare quality. The aim of this study was to analyze the impact of resident and fellow participation on postoperative complications in transsphenoidal pituitary surgery in a multi‐institutional setting.Study DesignRetrospective analysis of population‐based surgical registry.SettingAcademic medical center.MethodsThe American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was utilized to generate transsphenoidal pituitary surgery patient cohorts. The attending with resident and/or fellow group was compared to the attending alone based on demographics and preoperative and postoperative variables.ResultsA total of 469 cases were included in the analysis, with 315 performed with resident participation and 154 by attendings alone. The attending group had higher rates of diabetics (20.1% vs. 11.7%, P = 0.015) and patients with a history of previous percutaneous coronary intervention (6.0 vs. 1.6%, P = 0.009). Although the attending group demonstrated higher rates of surgical complications, and the resident/fellow group showed increased incidence in medical and overall complication rates, there was no statistical difference between the two groups. Multivariate analysis further demonstrated lack of significance in complication rates between attendings and residents/fellows.ConclusionResident and fellow participation in transsphenoidal surgery is not associated with significant differences in surgical complications, medical complications, mortality, operating time, reoperation rates, or readmission rates when compared to attendings.Level of Evidence4 Laryngoscope, 128:2707–2713, 2018
Utility of intraoral ultrasound in managing oral tongue squamous cell carcinoma: Systematic review
Authors: Tarabichi Osama , Bulbul Mustafa G. , Kanumuri Vivek V. , Faquin William C. , Juliano Amy F. , Cunnane Mary E. , Varvares Mark A. 
Published: August 2018

Objectives/HypothesisAdequate surgical resection of early stage oral tongue cancer provides the best chance at preventing locoregional disease recurrence. Determination of tumor dimensions and margin location is challenging and can lead to inadequate resections with close/positive margins. Ultrasonography has proven its utility in determining the thickness and extent of tongue tumors. Preoperative tumor dimension measurements carry increased significance with the addition of depth of invasion (DOI) to the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system. We report the results of a systematic review of the literature pertaining to the use of ultrasound in the diagnosis and management of oral tongue carcinoma.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta‐analysis statement checklist was used to inform the design of this systematic review. All studies that utilized ultrasound in the diagnosis/management of primary carcinoma of the oral tongue were included. PubMed, Embase, and Cochrane were reviewed to identify eligible studies.ResultsNineteen articles were included in our analysis. Six hundred seventy‐eight patients were studied in the articles included. Ultrasound tumor thickness measurements correlate well with those on histopathology and show promise as a predictor of cervical lymph node metastasis. Ultrasound can be safely used intraoperatively for deep margin assessment.ConclusionsUltrasound is useful in the evaluation of oral tongue malignancies. More experience is needed to determine if it is reliable in determining preoperative DOI in light of the role this tumor parameter plays in the eighth edition of the AJCC staging manual. Laryngoscope, 129:662–670, 2019
Permeability and Weibel–Palade Bodies of the Blood Vessels in the Human Vocal Fold Mucosa
Authors: Sato Kiminori , Chitose Shun‐ichi , Sato Kiminobu , Sato Fumihiko , Umeno Hirohito 
Published: August 2018

ObjectivesTransendothelial exchange and permeability of the capillaries in Reinke space (the superficial layer of the lamina propria) of the vocal fold mucosa affect physiological and pathological conditions of the human vocal fold mucosa. The mechanism of permeability and Weibel–Palade bodies of the blood vessels in the human vocal fold mucosa were investigated using electron microscopy.Study designHistologic analysis of the human vocal fold.MethodsSix normal human vocal folds (three adults and three newborns) obtained from autopsy cases and three human vocal folds with Reinke edema from surgical specimens were investigated under transmission electron microscopy.ResultsThere were three possible capillary wall transport systems related to the permeability of the blood vessels in the vocal fold mucosa: 1) Fenestra transport, plasma exuded from the capillaries into surrounding tissue via the fenestration with or without a diaphragm; 2) vesicular transport (transcellular transport via vesicles), the use of vesicles to ferry fluid and solutes across endothelial cells; and 3) junctional transport (intercellular transport), molecules passed through intercellular gaps between endothelial cells.Weibel–Palade bodies were present in the cytoplasm of endothelial cells both in adults and newborns. They were present in high numbers in the cytoplasm of endothelial cells, with intercellular transport in the vocal folds with Reinke edema.ConclusionThere were three types of mechanisms for the permeability of the blood vessels in the human vocal fold mucosa. Some physiologically active substances, such as histamine produced by Weibel–Palade bodies, may adversely influence the permeability of the blood vessels.Level of EvidenceNA. Laryngoscope, 2588–2592, 2018
Adjuvant Chemotherapy Is Associated With Improved Survival for Late‐Stage Salivary Squamous Cell Carcinoma
Authors: Cheraghlou Shayan , Schettino Amy , Zogg Cheryl K. , Otremba Michael D. , Bhatia Aarti , Park Henry S. , Osborn Heather A. , Mehra Saral , Yarbrough Wendell G. , Judson Benjamin L. 
Published: August 2018

ObjectiveSalivary squamous cell carcinomas (SCCs) represent a unique disease entity because many are thought to represent metastases from primary cutaneous malignancies. Nevertheless, they represent a significant proportion of parotid gland cancers and have a notably poor prognosis. Recently, there has been controversy regarding the utility of adjuvant chemotherapy in the treatment of these malignancies, with most studies concluding that there is no survival benefit. We aim to determine the outcomes associated with the use of adjuvant radiotherapy and chemoradiotherapy in the treatment of early‐ and late‐stage salivary SCC.MethodsA retrospective study of 2,285 of surgically resected adult salivary SCC diagnosed from 2004 to 2014 in the National Cancer Database was conducted. Patients were divided into early‐ (I/II) and late‐stage (III/IV) groups. Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate Cox survival regressions, propensity‐score matched analyses, and univariate Kaplan‐Meier analyses were conducted.ResultsThe use of adjuvant chemoradiotherapy for late‐stage patients was associated with improved survival compared to the use of adjuvant radiotherapy alone (hazard ratio [HR] 0.774, P = 0.026). Five‐year survival for late‐stage patients treated with surgery alone, surgery with adjuvant radiotherapy, and surgery with adjuvant chemoradiotherapy was 31.1% (standard error [SE]: 2.5), 45.6% (SE: 2.2), and 58.9% (SE: 3.4). Use of adjuvant therapy (either chemoradiotherapy or radiotherapy alone) was associated with improved survival for early‐stage patients (HR 0.746, P = 0.037).ConclusionThe addition of chemotherapy to the adjuvant therapy of late‐stage patients with salivary SCC may result in improved long‐term survival. Expanded use of adjuvant therapy for early‐stage disease may also improve patient outcomes.Level of Evidence4 Laryngoscope, 129:883–889, 2019
Free Flap Versus Pedicled Flap Reconstruction of Laryngopharyngeal Defects: A 10‐Year National Surgical Quality Improvement Program Analysis
Authors: Haidar Yarah M. , Kuan Edward C. , Verma Sunil P. , Goddard Julie A. , Armstrong William B. , Tjoa Tjoson 
Published: August 2018

Objectives/HypothesisLarge defects after total laryngectomy (TL) and total laryngopharyngectomy (TLP) often benefit from free flap (FF) or pedicled flap (PF) reconstruction to maintain continuity of the aerodigestive tract, protect great vessels, or reinforce pharyngeal closure. Although both techniques are commonly used, no consensus exists as to which results in fewer complications. The goal of this study was to determine if 30‐day morbidity/mortality outcomes differ between PF and FF reconstruction in patients undergoing TL/TLP.Study DesignRetrospective cohort study.MethodsPatients were analyzed who underwent TL/TLP with reconstruction using records from the American College of Surgeons National Surgical Quality Improvement Program database (2005–2015).ResultsA total of 347 patients were included; 204 received FF reconstruction, whereas 143 received PF reconstruction. FF reconstruction was more commonly used with TLP defects (P = .001). The total operative time in the FF (590 ± 140 minutes) was longer than the PF (441 ± 125 minutes) group (P < .0001). There was a higher rate of postoperative transfusions in those undergoing FF reconstruction (P = .022). There was no significant difference in complication rates among TLP patients. Among TL patients only, FF reconstruction had a higher association with wound infections than PFs (P = .040). On multivariate analysis, low hematocrit was associated with complications (P = .031). Age (P = .031) and congestive heart failure exacerbation (P < .001) were associated with increased hospital stay. Overall, there were no differences in readmissions, reoperations, or deaths between the groups.ConclusionsReported complication rates after TL/TLP remain high, despite widespread usage of vascularized flaps in reconstruction. This comparison reveals no significant difference in postoperative complications between patients who received PF and FF laryngopharyngeal reconstruction.Level of Evidence4 Laryngoscope, 129:105–112, 2019
Phantom limb pain: peripheral neuromodulatory and neuroprosthetic approaches to treatment
Authors: Petersen Bailey A. , Nanivadekar Ameya C. , Chandrasekaran Santosh , Fisher Lee E. 
Published: August 2018

ABSTRACTPost‐amputation phantom limb pain (PLP) is a widespread phenomenon that can have physical, psychological, and functional impacts on amputees who experience the condition. The varying presentations and mechanisms of PLP make it difficult to effectively provide long‐term pain relief. Multiple neuromodulatory approaches to treating PLP have focused on electrical stimulation of the peripheral nervous system, with varying degrees of success. More recently, research has been done to study the effects of neuroprosthetic approaches on PLP. Neuroprosthetics combine the use of a functional prosthetic with stimulation to the peripheral nerves in the residual limb. Although many of the neuroprosthetic studies focus on improving function, several have shown preliminary evidence for the reduction of severity of PLP. In this review we provide an overview of the current understanding of the neurological mechanisms that initiate and sustain PLP, as well as the neuromodulatory and neuroprosthetic approaches under development for treatment of the condition.Muscle Nerve59:154–167, 2019
Recent advances in thermally robust, late transition metal‐catalyzed olefin polymerization
Authors: Mitchell Nolan E , Long Brian K 
Published: August 2018

AbstractOlefin polymerization catalysts employing late transition metals, such as Ni, Pd, Fe and Co, have been heavily investigated since their discovery in the mid‐1990s. Despite the advantages and appeal these catalysts have displayed in academic research, their implementation in industry has remained restricted due to a variety of limitations and drawbacks. One specific limitation is the relative thermal instability of most late transition metal olefin polymerization catalysts at the temperatures commonly utilized for industrial polymerizations. This review focuses on the development of Ni‐, Pd‐, Fe‐ and Co‐based olefin polymerization catalysts that display increased thermal stability at super‐ambient reaction temperatures. These advances in thermal stability have been realized using a variety of ligand modifications, and their polymerization activities and thermal stability are summarized herein. Lastly, a brief outlook on the future of thermally stable, late transition metal olefin polymerization catalysts is provided. © 2018 Society of Chemical Industry
Triphenylamine and some of its derivatives as versatile building blocks for organic electronic applications
Authors: Blanchard Philippe , Malacrida Claudia , Cabanetos Clément , Roncali Jean , Ludwigs Sabine 
Published: August 2018

This review article gives an overview of past and current activities in the Linear Conjugated Systems Group of Angers and in the IPOC – Functional Polymers Group of the Institute of Polymer Chemistry of Stuttgart on the use of triphenylamine (TPA) as versatile building block for organic electronics. In the first part, the properties of TPA itself are introduced including geometrical and energy level considerations. Dimerization of TPA to tetraphenylbenzidine upon electrochemical oxidation is highlighted. The blocking of TPA para‐positions and its implications in terms of electroactivity is further discussed. The second part shows that dimerization of TPA as pendant redox‐active moieties in polymers is a versatile strategy to crosslink polymer films. Coming from redox homopolymers the crosslinking strategy is extended towards conjugated redox polymers based on polythiophenes and block copolymers. Conductivity mechanisms and the influence of doping level on conductivity are probed with cyclic voltammetry coupled with in situ conductance and four‐point probe measurements. The last part is dedicated to the use of TPA as an electron‐donating block in the design of donor‐π‐acceptor chromophores and their use as active material in organic photovoltaics. An overview of some relevant TPA‐based push–pull molecules from the literature and our contribution to this field is presented emphasizing the progress of the photovoltaic performance of organic solar cells made over the last decade. © 2018 Society of Chemical Industry
Unique auto‐ubiquitination activities of artificial RING fingers in cancer cells
Authors: Miyamoto Kazuhide , Nakatani Arisa , Sunagawa Mayumi , Saito Kazuki 
Published: August 2018

AbstractUbiquitin‐conjugating (E2) enzymes in protein ubiquitination are associated with various diseases. An artificial RING finger (ARF) is a useful tool, and E2 activities are conveniently estimated based on ARF reactivities. To extend the use of ARF in cells, we constructed a TAT‐ARF using a cell‐penetrating trans‐activator protein (TAT) peptide. An in vitro ubiquitination assay without substrates showed auto‐ubiquitination of TAT‐ARF via its TAT region. TAT‐ARF was translocated into MCF7 breast cancer cells, and then TAT‐ARF ubiquitinated itself via its ARF. Experiments using confocal laser‐scanning microscopy revealed that FAM‐labeled TAT‐ARF was readily internalized in cells and it remained encapsulated in vesicles. The Cell Counting Kit‐8 assay indicated that the TAT‐ARF uptake occurred without cytotoxicity in MCF7 cells at concentrations below 5.0 μM. By taking advantage of TAT‐ARF, we, for the first time, succeeded in detecting E2 activities in cells. Thus, the present work opens up new avenues in the investigation of protein ubiquitination.
The N‐terminal methyltransferase homologs NRMT1 and NRMT2 exhibit novel regulation of activity through heterotrimer formation
Authors: Faughn Jon D. , Dean William L. , Schaner Tooley Christine E. 
Published: August 2018

AbstractProtein, DNA, and RNA methyltransferases have an ever‐expanding list of novel substrates and catalytic activities. Even within families and between homologs, it is becoming clear the intricacies of methyltransferase specificity and regulation are far more diverse than originally thought. In addition to specific substrates and distinct methylation levels, methyltransferase activity can be altered by complex formation with close homologs. We work with the N‐terminal methyltransferase homologs NRMT1 and NRMT2. NRMT1 is a ubiquitously expressed distributive trimethylase. NRMT2 is a monomethylase expressed at low levels in a tissue‐specific manner. They are both nuclear methyltransferases with overlapping consensus sequences but have distinct enzymatic activities and tissue expression patterns. Co‐expression with NRMT2 increases the trimethylation rate of NRMT1, and here we aim to understand how this occurs. We use analytical ultracentrifugation to show that while NRMT1 primarily exists as a dimer and NRMT2 as a monomer, when co‐expressed they form a heterotrimer. We use co‐immunoprecipitation and molecular modeling to demonstrate in vivo binding and map areas of interaction. While overexpression of NRMT2 increases the half‐life of NRMT1, the converse is not true, indicating that NRMT2 may be increasing NRMT1 activity by stabilizing the enzyme. Accordingly, the catalytic activity of NRMT2 is not needed to increase NRMT1 activity or increase its affinity for less preferred substrates. Monomethylation can also not rescue phenotypes seen with loss of trimethylation. Taken together, these data support a model where NRMT2 expression activates NRMT1 activity, not through priming, but by increasing its stability and substrate affinity.