bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival of patients with head and neck cancer with metachronous multiple primary tumors is surprisingly favorable
Authors: Bugter Oisín , van Iwaarden Dirk L.P. , Dronkers Emilie A.C. , de Herdt Martine J. , Wieringa Marjan H. , Verduijn Gerda M. , Mureau Marc A.M. , ten Hove Ivo , van Meerten Esther , Hardillo José A. , Baatenburg de Jong Robert J. 
Published: January 2019

AbstractBackgroundThe objectives of this study are to determine the incidence and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) with multiple primary tumors (MPT) in the HN‐region, lung, or esophagus.MethodsPatient and tumor specific data of 1372 patients with HNSCC were collected from both the national cancer registry and patient records to ensure high‐quality double‐checked data.ResultsThe total incidence of MPTs in the HN‐region, lung, and esophagus in patients with HNSCC was 11% (149/1372). Patients with lung MPTs and esophageal MPTs had a significant worse 5‐year survival than patients with HN‐MPTs (29%, 14%, and 67%, respectively, P < 0.001). The 5‐year survival rate for synchronous HN MPTs was only 25%, whereas it was surprisingly high for patients with metachronous HN MPT (85%, P < 0.001).ConclusionsOne of 10 patients with HNSCC develop MPTs in the HN‐region, lung, or esophagus. The 5‐year survival of patients with metachronous HN MPTs was surprisingly favorable.
The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes
Authors: Pavón Miguel Angel , Arroyo‐Solera Irene , León Xavier , Téllez‐Gabriel Marta , Virós David , Gallardo Alberto , Céspedes Maria Virtudes , Casanova Isolda , Lopez‐Pousa Antonio , Barnadas Agustí , Quer Miquel , Mangues Ramón 
Published: January 2019

AbstractBackgroundWe aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial‐like (EL) or mesenchymal‐like (ML) phenotypes.Materials and methodsWe analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival.ResultsEL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93‐gene expression signature between ML and EL cells was used to build a three‐gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA‐seq data of the TCGA‐HNSC project. Its prognostic value was confirmed in two independent cohorts.ConclusionEFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.
Durable intracranial and extracranial response to nivolumab with appearance of secondary resistance in a heavily pretreated patient with head and neck cancer
Authors: Cabezas‐Camarero Santiago , García‐Barberán Vanesa , Sáiz‐Pardo Sanz Melchor , Cabrera‐Martín María Nieves , Gimeno‐Hernández Jesús , Pérez‐Segura Pedro 
Published: January 2019

AbstractBackgroundRecently, nivolumab was approved in the second‐line setting of squamous cell cancer of the head and neck (SCCHN). The benefits of PD‐(L)1 inhibitors in PD‐L1(−) tumors are unclear, and no reports exist on the activity of these agents in brain metastases from SCCHN. Little is known regarding the mechanisms underlying acquired resistance to PD‐(L)1 inhibition.MethodsA patient with PD‐L1(−) metastatic SCCHN progressing to cetuximab‐based chemotherapy received third‐line nivolumab. T cell infiltration and mRNA expression of immune‐related genes were compared in prenivolumab and postnivolumab biopsies from a progressing tumor lesion.ResultsAn exceptional local and systemic response was achieved, including complete devitalization of brain metastases that lasted for more than a year. Increased T cell infiltration and upregulation of genes related to T cell exhaustion and resistance to PD‐1 inhibition were found.ConclusionDurable responses to PD‐(L)1 inhibitors may be observed in biomarker‐negative SCCHN. Mechanisms of resistance should be studied.
Not CD68 but stabilin‐1 expression is associated with the risk of recurrence in patients with oral cavity squamous cell carcinoma
Authors: Kwon Minsu , Yeo Seong Chul , Lee Jong Sil , Park Jung Je 
Published: January 2019

AbstractBackgroundThis study's aim was to identify CD68 and stabilin‐1 expressions and their prognostic implications in patients with oral cavity cancer (OCC).MethodsStabilin‐1 and CD68 immunochemical staining was conducted in samples from patients with OCC who underwent curative surgery in our institute. We retrospectively analyzed patients' clinical information. We investigated the relationship between CD68 and stabilin‐1 expression levels and their effect on prognostic factors and survival.ResultsFifty‐four patients' data were analyzed. CD68 and stabilin‐1 expressions were positively correlated (P = .008). CD68 and stabilin‐1 expressions were not correlated with other prognostic factors (eg, T classification or lymph node metastasis). Stabilin‐1 expression and tumor recurrence risk were positively correlated (P = .015). CD68 expression was neither associated with recurrence‐free nor OCC‐specific survival.ConclusionCD68 and stabilin‐1 expressions in OCC were positively correlated. Stabilin‐1 expression was significantly associated with OCC recurrence risk, but the prognostic value of CD68 was not confirmed.
Louis Pasteur, Chemist: An Account of His Studies of Cinchona Alkaloids
Authors: Gal Joseph 
Published: January 2019

AbstractPasteur carried out pioneering work on cinchona alkaloids and their derivatives and his studies led to important discoveries. He examined crystals of cinchona alkaloids for his correlation of crystal hemihedrism with molecular chirality, studies that led Pasteur to the discovery of physicochemical differences between diastereoisomeric salts of tartaric acids with optically active cinchona bases, an important insight into fundamentals of molecular chirality. These physicochemical differences also led to Pasteur’s invention of the vital method of racemate resolution through diastereoisomeric derivatives. Pasteur clarified the confusion around the cinchona alkaloids by elucidating their identities and relations. He discovered the conversion of the major cinchona alkaloids to quinicine and cinchonicine, a finding subsequently of considerable importance in studies of the structure and synthesis of the major cinchona alkaloids. The reaction producing quinicine and cinchonicine led Pasteur to the discovery of the racemization of tartaric acid and the finding of meso‐tartaric acid, fundamental breakthroughs in the development of stereochemistry.
Platelet‐derived growth factor‐D expression mediates the effect of differentiated degree on prognosis in epithelial ovarian cancer
Authors: Yang Chunyan , Zhang Mengjun , Cai Yuqing , Rong Zhiwei , Wang Ce , Xu Zhenyi , Xu Huan , Song Wei , Hou Yan , Lou Ge 
Published: January 2019

AbstractPlatelet‐derived growth factor‐D (PDGF‐D) can enhance invasion and metastasis in several human malignancies. Although several studies have been performed to investigate the association between clinicopathological characteristics and prognosis in epithelial ovarian cancer (EOC), the mediation effect of PDGF‐D on above‐mentioned association have been seldom assessed. In this study, we detected the PDGF‐D expression from the tissues of patients with EOC and further collected clinicopathological characteristics and prognostic information to identify whether PDGF‐D mediated the effect of differentiated degree on prognosis in patients with EOC. A total of 190 paraffin‐embedded tissue samples from patients with EOC between July 2005 and December 2010 were collected. We performed a Kaplan‐Meier analysis for the association between differentiated degree and prognosis followed by a causal mediation analysis. The analysis results indicated that differentiated degree was associated with prognosis and PDGF‐D mediated the effect of differentiated degree on prognosis in patients with EOC, which might be a potential target for ovarian cancer treatment.
MicroRNA‐29b regulates hypertrophy of murine mesenchymal stem cells induced toward chondrogenesis
Authors: Zhao Chunrong , Miao Ying , Cao Zhen , Shi Jian , Li Jianmei , Kang Fei , Dou Ce , Xie Zhao , Xiang Qiang , Dong Shiwu 
Published: January 2019

AbstractObjectiveChondrocyte hypertrophy, a terminal stage of chondrocyte differentiation, is essential to the endochondral bone formation and is one of the major pathological factors in osteoarthritis. This study investigated the role of microRNA‐29b (miR‐29b), which is involved in chondrogenesis, in the regulation of hypertrophy in chondrocytes.MethodsmiR‐29b expression was assessed during murine mesenchymal stem cells (mMSCs) chondrogenesis. To detect whether miR‐29b affects chondrocyte hypertrophy, the mMSCs induced toward chondrogenesis were transfected with miR‐29b or its antisense inhibitor (antagomiR‐29b). Finally, the differential effects of antagomiR‐29b on chondrocytes at different differentiation stages were evaluated by loss‐of‐function experiments.ResultsmiR‐29b expression was low‐level during the early chondrogenic differentiation, however, it was changed to high level during hypertrophy. Subsequently, the gain‐of‐function and loss‐of‐function experiments had confirmed that miR‐29b promoted hypertrophy in mMSC‐derived chondrocytes. In addition, we confirmed that on day 7, when cells were treated with antagomiR‐29b, was the optimal intervention time for preventing hypertrophic phenotype of mMSCs in vitro.ConclusionmiR‐29b regulated chondrogenesis homeostasis and enhance hypertrophic phenotype. These data suggest that miR‐29b is a key regulator of the chondrocyte phenotype derived from mMSCs and it might be a potential target for articular cartilage repair.
Silence of  lncRNA UCA1 rescues drug resistance of cisplatin to non–small‐cell lung cancer cells
Authors: Liu Xiaojing , Huang Zhisheng , Qian Wei , Zhang Qing , Sun Jian 
Published: January 2019

AbstractThe aim of this study was to investigate the effect of long noncoding RNA (lncRNA) urogenital carcinoma antigen 1 (UCA1) on drug resistance in A549/DDP cell and explore its underlying mechanism. The inhibition rate and IC
50 of DDP were detected in A549 and A549/DDP cells by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide assay. The expression of lncRNA UCA1 was measured in A549 and A549/DDP cells by quantitative real‐time polymerase chain reaction. The expressions of N‐cadherin, E‐cadherin, vimentin, and Snail were detected in A549 and A549/DDP cells by Western blot analysis. Results showed that the IC
50 of DDP was 16.20 ± 2.27 μmol/L and 69.72 ± 4.83 μmol/L in A549 and A549/ DDP cells, respectively. Compared with the A549 group, the expressions of N‐cadherin, vimentin, and Snail was significantly upregulated in A549/DDP group, but E‐cadherin was significantly downregulated. Compared with the shCon group, the abundance of N‐cadherin, vimentin, and Snail was significantly downregulated in short hairpin RNA UCA1 (shUCA1) group, while E‐cadherin was significantly upregulated. Cell migration and invasion were significantly suppressed and IC
50 was reversed to 16.20 ± 2.27 μmol/L in the shUCA1 group. Silencing lncRNA UCA1 inhibited the migration and invasion of A549/DDP cells and reversed the resistance of A549/DDP cells to DDP. The mechanism might be related to downregulation of epithelial‐mesenchymal transition, which will provide a new direction for the treatment of non–small‐cell lung cancer with cisplatin.
Menadione‐induced apoptosis in U937 cells involves Bid cleavage and stefin B degradation
Authors: Božič Janja , Bidovec Katja , Vizovišek Matej , Dolenc Iztok , Stoka Veronika 
Published: January 2019

AbstractEarlier studies showed that the oxidant menadione (MD) induces apoptosis in certain cells and also has anticancer effects. Most of these studies emphasized the role of the mitochondria in this process. However, the engagement of other organelles is less known. Particularly, the role of lysosomes and their proteolytic system, which participates in apoptotic cell death, is still unclear. The aim of this study was to investigate the role of lysosomal cathepsins on molecular signaling in MD‐induced apoptosis in U937 cells. MD treatment induced translocation of cysteine cathepsins B, C, and S, and aspartic cathepsin D. Once in the cytosol, some cathepsins cleaved the proapoptotic molecule, Bid, in a process that was completely prevented by E64d, a general inhibitor of cysteine cathepsins, and partially prevented by the pancaspase inhibitor, z‐VAD‐fmk. Upon loss of the mitochondrial membrane potential, apoptosome activation led to caspase‐9 processing, activation of caspase‐3‐like caspases, and poly (ADP‐ribose) polymerase cleavage. Notably, the endogenous protein inhibitor, stefin B, was degraded by cathepsin D and caspases. This process was prevented by z‐VAD‐fmk, and partially by pepstatin A‐penetratin. These findings suggest that the cleaved Bid protein acts as an amplifier of apoptotic signaling through mitochondria, thus enhancing the activity of cysteine cathepsins following stefin B degradation.
Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells
Authors: Qiu Rubiao , Ma Gang , Li Xueyu , Shi Qunfeng , Li Xinning , Zhou Xiong , Tang Yuanyuan , Xie Zhaodi , Liao Shijie , Qin Yiwu , Wang Ruyue , Ye Yu , Luo Jiefeng , Zhang Jianfeng 
Published: January 2019

AbstractOsteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC‐exerted benefits for anti‐OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor‐xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non‐OS controls, human OS samples showed increased levels of neoplastic microRNA‐223 (miR‐223), and elevated expressions of NF‐κBp65, IκBα proteins in tumor cells. In cell culture study, CC‐treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR‐223 level. Immunolabeled cells of proliferating cell nuclear antigen, B‐cell lymphoma 2 (Bcl‐2), poly(ADP‐ribose) polymerase (PARP) in CC treatments were decreased dose‐dependently, while caspase‐3 positive cells were elevated. Further, protein expressions of NF‐κBp65, IκBα in CC‐treated cells were downregulated. In addition, tumor‐xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR‐223 levels, and Bcl‐2, PARP‐positive cells, as well as downregulations of NF‐κBp65, IκBα protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR‐223‐IκBα signaling pathway in neoplastic cells.
AZD8835 inhibits osteoclastogenesis and periodontitis‐induced alveolar bone loss in rats
Authors: Wang Yexin , Chen Xuzhuo , Chen Xinwei , Zhou Zhihang , Xu Weifeng , Xu Feng , Zhang Shanyong 
Published: January 2019

AbstractChronic periodontitis (CP) is one of the most common oral diseases, which is characterized by the loss of connective tissue and alveolar bone in adults. AZD8835, a novel dual phosphoinositide‐3‐kinase (PI3K) inhibitor, is currently in phase 1 clinical evaluation to treat breast cancer. However, whether AZD8835 has any effect on teeth and alveolar bone health remains unclear. In the current study, we aimed to investigate the potential effect of AZD8835 in treating CP in vitro and in vivo. We found that AZD8835 could inhibit osteoclast differentiation, bone resorption, and downregulate the expression of osteoclast marker genes, such as tartrate‐resistant acid phosphatase (Trap), cathepsin K (Ctsk), V‐ATPase d2 (Atp6v0d2), and calcitonin receptor (Ctr). In addition, AZD8835 suppressed osteoclastogenesis by inhibiting receptor activator of nuclear factor kappa B ligand (RANKL)‐induced PI3K/protein kinase B (AKT), extracellular signal‐regulated kinase, and nuclear factor‐κB signaling in BMMs. In vivo, AZD8835 greatly ameliorated alveolar bone (ABL) loss in rats with CP. Meanwhile, histological examination showed fewer osteoclasts in the treatment group. In conclusion, these results indicated that AZD8835 is a promising agent to reduce ABL in CP.
Efficacy and acceptability of neoadjuvant endocrine therapy in patients with hormone receptor‐positive breast cancer: A network meta‐analysis
Authors: Zhang Tingting , Feng Fubin , Yao Yan , Qi Lingyu , Tian Jinhui , Zhou Chao , Dong Shengjie , Wang Xue , Sun Changgang 
Published: January 2019

AbstractBackgroundThe optimal sequence of endocrine therapy in a neoadjuvant setting for hormone receptor‐positive (HR+) breast cancer is unclear. Our study evaluated the efficacy and acceptability of neoadjuvant endocrine therapy for HR+ breast cancer.MethodsWe identified studies based on titles and abstracts that were published before 22 June 2018 in the following databases: PubMed, EMBASE, and the Cochrane Library. Eligible studies were randomised controlled trials with at least one arm that evaluated the effectiveness of one or a combination of anastrozole, letrozole, palbociclib, tamoxifen, fulvestrant, abemaciclib, everolimus, gefitinib, ribociclib, taselisib, and exemestane. We pooled effect sizes using the odds ratio (OR) and corresponding 95% credibility interval (95% CrI). The primary outcomes were response rate and treatment completion.ResultsOur network meta‐analysis included 3,306 participants and 16 eligible studies, which assessed 15 treatments. In terms of response rates, compared with letrozole combined therapy, tamoxifen was associated with a significant reduction in response rate (OR, 0.34; 95% CrI, 0.13–0.85; OR, 0.32; 95% CrI, 0.13–0.80; OR, 0.26; 95% CrI, 0.09–0.83; and OR, 0.30; 95% CrI, 0.09–0.96; for letrozole plus everolimus, letrozole plus taselisib, letrozole plus zoledronic acid, and letrozole plus lapatinib, respectively). Based on the surface under the cumulative ranking curves ranking, letrozole plus zoledronic acid was associated with the highest rate of response (87.6%), followed by letrozole plus lapatinib (85.2%), and letrozole plus taselisib (79.3%).ConclusionsUltimately, our study established that letrozole plus zoledronic acid may be an optimal treatment based on its current rank in a neoadjuvant setting for HR+ breast cancer.
Impact of hyperoxia on cardiac pathophysiology
Authors: Rodgers Jennifer L. , Iyer Drishya , Rodgers Lydia E. , Vanthenapalli Sahit , Panguluri Siva K. 
Published: January 2019

AbstractMechanical ventilation with high oxygen therapy (hyperoxia) is widely implemented in critical care and ICU settings. Although supplemental oxygen is beneficial to treat hypoxia, its use is also associated with poor outcomes and high mortality in patients. Lung injury due to hyperoxia exposure has been well‐documented in patients, including in adults and neonates. Thus, lung injury due to hyperoxia has been extensively researched in both preclinical and clinical studies. However, hyperoxia has also been shown to be associated with hemodynamic changes in patients in ICU, including reductions in heart rate, stroke volume, and cardiac output. In addition, certain experimental studies report that hyperoxia exposure in neonates results in cardiac dysfunction in later adult life. Despite this, until recently, the impact of hyperoxia within the heart has not been well studied, or reported, specifically in adult experimental models. To close this significant gap, our lab has sought to clarify hyperoxia‐induced cardiac pathophysiology in adult murine models. This review discusses the current findings regarding the cardiovascular impact of hyperoxia exposure.
An efficient multi‐destinations trip planning protocol for intelligent transport system
Authors: Siam Hisham , Bani Younes Maram 
Published: January 2019

AbstractTargeting several destinations on the same trip is commonly seen over the downtown areas. Several drivers leave their home or work everyday targeting multiple end‐destinations for shopping or entertaining purposes. The sequence of visiting destinations can be selected randomly by the drivers, especially if they are less familiar with the area of interest or with multi‐destinations trips. However, expert drivers that travel more frequently towards several destinations should be more cautious planning their trips. They consider the relative locations of these end‐destinations and use their historical knowledge regarding the traffic over the connected road segments there. This paper proposes an efficient multi‐destinations trip planning protocol (MDPP) that recommends drivers with the best sequence of destinations to visit. The proposed protocol considers the location of each destination and the relative distance between all located destinations. It also considers the traffic distribution over the investigated areas of interest to recommend drivers to avoid highly congested road segments or road segments that suffer traffic issue such as accident or emergency existence. From the experimental results, we can see that the MDPP protocol has selected the best path towards the targeted destinations compared with other common selected sequences. It has decreased the travel time, fuel consumption, and the gas emissions for different investigated scenarios.
Molecular signatures of chronic periodontitis in gingiva: A genomic and proteomic analysis
Authors: Guzeldemir‐Akcakanat Esra , Alkan Begum , Sunnetci‐Akkoyunlu Deniz , Gurel Busra , Balta V. Merve , Kan Bahadir , Akgun Emel , Yilmaz Elif Busra , Baykal Ahmet Tarik , Cine Naci , Olgac Vakur , Gumuslu Esen , Savli Hakan 
Published: January 2019

AbstractBackgroundTo elucidate molecular signatures of chronic periodontitis (CP) using gingival tissue samples through omics‐based whole‐genome transcriptomic and whole protein profiling.MethodsGingival tissues from 18 CP and 25 controls were analyzed using gene expression microarrays to identify gene expression patterns and the proteins isolated from these samples were subjected to comparative proteomic analysis by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The data from transcriptomics and proteomics were integrated to reveal common shared genes and proteins.ResultsThe most upregulated genes in CP compared with controls were found as MZB1, BMS1P20, IGLL1/IGLL5, TNFRSF17, ALDH1A1, KIAA0125, MMP7, PRL, MGC16025, ADAM11, and the most upregulated proteins in CP compared with controls were BPI, ITGAM, CAP37, PCM1, MMP‐9, MZB1, UGTT1, PLG, RAB1B, HSP90B1. Functions of the identified genes were involved cell death/survival, DNA replication, recombination/repair, gene expression, organismal development, cell‐to‐cell signaling/interaction, cellular development, cellular growth/proliferation, cellular assembly/organization, cellular function/maintenance, cellular movement, B‐cell development, and identified proteins were involved in protein folding, response to stress, single‐organism catabolic process, regulation of peptidase activity, and negative regulation of cell death. The integration and validation analysis of the transcriptomics and proteomics data revealed two common shared genes and proteins, MZB1 and ECH1.ConclusionIntegrative data from transcriptomics and proteomics revealed MZB1 as a potent candidate for chronic periodontitis.