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Histopathological Evidence for Irradiation Angiopathy in Head and Neck Cancer

International Journal of Otolaryngology and Head & Neck surgery 2015年第2期4卷 108-114页

作者： Nobuhiro Uwa Hiroyuki Hao Yoshitane Tsukamoto Tomonori Terada Kosuke Sagawa Takeshi Mohri Takashi Daimon Hiroshi Doi Yohei Sotsuka Guillaume van Eys Marie-Luce Bochaton-Piallat Seiichi Hirota Masafumi Sakagami Department of Otolaryngology Hyogo College of Medicine Nishinomiya Japan Department of Surgical Pathology Hyogo College of Medicine Nishinomiya Japan Department of biostatistics Hyogo College of Medicine Nishinomiya Japan Department of Radiology Hyogo College of Medicine Nishinomiya Japan Department of Plastic surgery Hyogo College of Medicine Nishinomiya Japan Department of Genetics and Cell Biology University of Maastricht Maastricht The Netherlands Department of Pathology and Immunology University of Geneva-CMU Geneva Switzerland

Objective: To evaluate the incidence of cervical angiopathy caused by radiation therapy for head and neck cancer. Methods: Segments of 57 cervical arteries were obtained during surgery for head and neck malignant tumors and divided into two groups (irradiated group and non-irradiated group) based on the treatment prior to vascular resection. In order to evaluate vascular injury after radiation therapy, we examined the degree of medial atrophy, medial fibrosis, smooth muscle cell (SMC) differentiation in the media and intima, intimal hyperplasia and endothelial cell (EC) injury. Sections of arterial segments were stained with hematoxylin-eosin, Elastica van Gieson and Masson’s trichrome, and immunohistochemistry for α-smooth muscle actin (α-SMA), smoothelin, S100A4 and CD31 in the resected vessels was conducted. Results: The median interval between the completion of radiation therapy and vascular resection was nine months. No significant differences were observed between the two groups in terms of medial atrophy, medial fibrosis and intimal hyperplasia. The ratio of the smoothelin-positive area per α-SMA-positive area in the media and the S100A4-positive proportion in the intima, indicating the degree of differentiation of the medial SMC and dedifferentiation of the intimal SMC, respectively, showed no significant differences, despite the tendency toward a lower smoothelin-positive area per α-SMA-positive area in the media of the irradiated arteries. The EC coverage revealed on CD31 immunohistochemistry was significantly decreased, with mural thrombus adhesion, in the irradiated group. Conclusions: The ECs of small arteries are damaged by irradiation. Although we did not confirm the statistical significance of medial SMC dedifferentiation, a decreased expression of smoothelin tended to be observed in the media of the irradiated arteries. Our findings provide histopathological evidence of irradiation angiopathy in head and neck cancer and may help to improve the surgi

关键词： Angiopathy Endothlial Cell Pathology Radiation Head and Neck

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From tuberculosis bedside to bench:UBE2B splicing as a potential biomarker and its regulatory mechanism

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1282-1295页

作者： Mengyuan Lyu Jian Zhou Yanbing Zhou Weelic Chong Wei Xu Hongli Lai Lu Niu Yang Hai Xiaojun Yao Sheng Gong Qinglan Wang Yi Chen Yili Wang Liyu Chen Zengwanggema Jiongjiong Zeng Chengdi Wang Binwu Ying Department of Laboratory Medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Thoracic surgery West China HospitalSichuan UniversityChengduSichuan 610041China Sidney Kimmel Medical College Thomas Jefferson UniversityPhiladelphiaPA 19107USA Department of biostatistics Princess Margaret Cancer CentreUniversity Health NetworkTorontoOntario M5G 1L7Canada Dalla Lana School of Public Health University of TorontoTorontoON M5T 3M7Canada Institute of Thoracic Oncology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Radiology Thomas Jefferson University HospitalPhiladelphiaPA 19107USA Department of Thoracic surgery The Public and Health Clinic Centre of ChengduChengduSichuan 610066China Department of Respiratory and Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengduSichuan 610213China Department of Infectious Diseases West China HospitalSichuan UniversityChengduSichuan 610041China Zhaojue People’s Hospital of Liangshan Prefecture Liangshan PrefectureSichuan 616150China Department of Laboratory Medicine Ganzi People’s HospitalGanzi PrefectureSichuan 626099China

Alternative splicing(AS)is an important approach for pathogens and hosts to remodel ***,tuberculosis(TB)-related AS has not been sufficiently *** we presented the first landscape of TB-related AS by long-read sequencing,and screened four AS events(S100A8-intron1-retention intron,RPS20-exon1-alternaitve promoter,KIF13B-exon4-skipping exon(SE)and UBE2B-exon7-SE)as potential biomarkers in an in-house *** validations in an in-house cohort-2(2274 samples)and public datasets(1557 samples)indicated that the latter three AS events are potential promising biomarkers for TB diagnosis,but not for TB progression and *** excellent performance of classifiers further underscored the diagnostic value of these three *** analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable *** splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 *** heat-killed mycobacterium tuberculosis stimulation,231 ubiquitination proteins in macrophages were differentially expressed,and most of them are apoptosis-related *** together,we depicted a global TB-associated splicing profile,developed TB-related AS biomarkers,demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing,offering a novel insight into the pathophysiology of TB.

关键词： tuberculosis stimulation diagnosis

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Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans

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四川生理科学杂志 2021年第10期43卷 1746-1746页

作者： Barbra A Dickerman From CAUSALab (B.A.D. A.L.M. M.A.H.) and the Departments of Epidemiology (B.A.D. A.L.M. M.A.H.) and Biostatistics (M.A.H.) Harvard T.H. Chan School of Public Health Massachusetts Veterans Epidemiology Research and Information Center Veterans Affairs Boston Healthcare System (H.G. K.E.K. B.R.F. M.J.F.M. D.R.G. J.M.G. K.C. J.P.C.) the Department of Surgery (A.L.M.) and Division of Aging (J.M.G. K.C. J.P.C.) Brigham and Women’s Hospital Harvard Medical School and the Department of Biostatistics (M.J.F.M. D.R.G.) Boston University School of Public Health — all in Boston.

Background:The messenger RNA(mRNA)-based vaccines BNT162b2 and mRNA-1273 are more than 90%effective against coronavirus disease 2019(Covid-19).However,their comparative effectiveness for a range of outcomes across diverse populations is ***:We emulated a target trial using the electronic health records of *** who received a first dose of the BNT162b2 or mRNA-1273 vaccine between January 4 and May 14,2021,during a period marked by predominance of the SARSCoV-2 B.1.1.7(alpha)*** matched recipients of each vaccine in a 1:1 ratio according to their risk *** included documented severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,symptomatic Covid-19,hospitalization for Covid-19,admission to an intensive care unit(ICU)for Covid-19,and death from *** estimated risks using the Kaplan-Meier *** assess the influence of the B.1.617.2(delta)variant,we emulated a second target trial that involved veterans vaccinated between July 1 and September 20,2021.

关键词： U.S. matched admission

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Usage of Cox-Regression Model for Forecasting of Survival Rate in Patients with the Early Stage of Non-Small Cell Lung Cancer

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Advances in Lung Cancer 2014年第1期3卷 26-33页

作者： Oleksey P. Kolesnik Anatoliy I. Shevchenko Yuriy E. Lyakh Vitaliy G. Gurianov Pavel A. Alyoshechkin Department of Medical Biophysics Medical Informatics and Biostatistics M. Gorky Donetsk National Medical University Donetsk Ukraine Department of Oncology Zaporizhzhya State Medical University Zaporizhzhya Ukraine

In the past decades a lot of investigations were focused on searching for more accurate markers of lung cancer progression. Researchers indicate that molecular markers may be useful in forecasting of treatment outcome and overall survival rate in patients with non-small cell lung cancer. The aim of our research was to create a forecasting model in order to identify patients with stage I-II of non-small cell lung cancer and dismal prognosis. Our research covered 254 patients with the early stage of non-small cell lung cancer who underwent a cure from June 2008 till December2012 inthe Department of Thoracic surgery of Zaporizhzhia Regional Clinical Oncologic Dispensary. surgery was performed for all patients. Adjuvant chemotherapy was performed for 101 patients. In order to carry out multivariate Cox-regression analysis, STATISTICA 6.0 (StatSoft Inc.) program was used. The most significant from 39 variables were selected (tumor size, histological form of tumor, volume of surgical intervention, volume of conducted lymph node dissection, Ki-67 expression, EGFR expression, E-cadherin expression). We propose the computer system which can forecast survival rate in patients with the early stage of non-small cell lung cancer.

关键词： Forecasting Model Survival Rate Non-Small Cell Lung Cancer

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Forecasting of Survival Rate in Patients with the Early Stage of Non Small Cell Lung Cancer

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Journal of Cancer Therapy 2013年第10期4卷 1472-1477页

作者： Oleksey P. Kolesnik Anatoliy I. Shevchenko Yuriy E. Lyakh Vitaliy G. Gurianov Department of Medical Biophysics Medical Informatics and Biostatistics M. Gorky Donetsk National Medical University Donetsk Ukraine Department of Oncology Zaporizhzhya State Medical University Zaporizhzhya Ukraine

Lung cancer is the most common cause of death from oncological diseases all over the world. Primary treatment of patients with the early stage of non-small cell lung cancer is a surgery. However, after surgery 30% - 85% of patients undergo disease progression. In order to improve the results of treatment of patients with non-small cell lung cancer it is necessary to separate a group of patients with dismal prognosis for whom adjuvant chemotherapy will permit improving the survival rate. The aim of our research was to create a forecasting model with a view to detect the patients with the early stage of non-small cell lung cancer and dismal prognosis. Our research covered 254 patients with the early stage of non-small cell lung cancer who underwent a cure from June 2008 till December 2012 in the department of thoracic surgery of Zaporizhzhia Regional Clinical Oncologic Dispensary. In order to identify the factors connected with the risks of low survival rate of patients with the early stage of non-small cell lung cancer after curative treatment (surgical treatment, adjuvant chemotherapy), a method of design of neural network models of classification was used. 39 factors were taken for input characteristics. During investigation two forecasting models were built. As follows from the analysis of first forecasting model with the increase of the patient’s BMI, the risk of low patient survival rate statistically and significantly (p = 0.03) decreases, OR = 0.89 (95% CI 0.80 - 0.99) for each kg/m2 index value. The risk of low patient survival rate also decreases (p = 0.02) if he has a squamous cell carcinoma, OR = 0.36 (95% CI 0.15 - 0.88) compared with other histological forms of tumor. The connection between the risk of low patient survival rate and the volume of surgical intervention was discovered (p = 0.01), OR = 3.19 (95% CI 1.29 - 7.86) for patients who underwent a pulmonectomy compared with patients who underwent an upper bilobectomy. As follows from the analysis of

关键词： Forecasting Model Survival Rate Non-Small Cell Lung Cancer

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External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children:A multicenter randomized controlled trial

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World Journal of Gastrointestinal surgery 2023年第4期15卷 712-722页

作者： Jing-Qing Zeng Tian-Ao Zhang Kai-Hua Yang Wen-Yu Wang Jia-Yu Zhang Ya-Bin Hu Jian Xiao Zhi-Jian Gu Biao Gong Zhao-Hui Deng Department of Gastroenterology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Clinical Epidemiology and biostatistics Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Gastroenterology Shanghai Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 200021China

BACKGROUND Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography(ERCP).Currently,there is no suitable treatment for post-ERCP pancreatitis(PEP)*** studies have prospectively evaluated interventions to prevent PEP in *** To assess the efficacy and safety of the external use of mirabilite to prevent PEP in *** This multicenter,randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility *** were randomly divided into the external use of mirabilite group(external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP)and blank *** primary outcome was the incidence of *** secondary outcomes included the severity of PEP,abdominal pain scores,levels of serum inflammatory markers[tumor necrosis factor-alpha(TNF-α)and serum interleukin-10(IL-10)],and intestinal barrier function markers[diamine oxidase(DAO),D-lactic acid,and endotoxin].Additionally,the side effects of topical mirabilite were *** total of 234 patients were enrolled,including 117 in the external use of mirabilite group and theother 117 in the blank *** pre-procedure and procedure-related factors were notsignificantly different between the two *** incidence of PEP in the external use ofmirabilite group was significantly lower than that in the blank group(7.7%vs 26.5%,P<0.001).The severity of PEP decreased in the mirabilite group(P=0.023).At 24 h after the procedure,thevisual analog scale score in the external use of mirabilite group was lower than that in the blankgroup(P=0.001).Compared with those in the blank group,the TNF-αexpressions weresignificantly lower and the IL-10 expressions were significantly higher at 24 h after the procedurein the external use of mirabilite group(P=0.032 and P=0.011,respectively).There were nosignificant differences in serum DAO,D-lactic acid,and endotox

关键词： Children Endoscopic retrograde cholangiopancreatography Mirabilite Chronic pancreatitis Post-endoscopic retrograde cholangiopancreatography pancreatitis Randomized controlled trial

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Innate immunity and hepatocarcinoma:Can toll-likereceptors open the door to oncogenesis?

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World Journal of Hepatology 2016年第3期8卷 162-182页

作者： Jorge AndréGomes Lopes Marta Borges-Canha Pedro Pimentel-Nunes Department of Physiology and Cardiothoracic surgery Cardiovascular Research and Development UnitFaculty of MedicineUniversity of Porto4200-319 PortoPortugal Gastroenterology Department Portuguese Oncology Institute4200-072 PortoPortugal CINTESIS/Department of biostatistics and Medical Informatics Faculty of MedicineUniversity of Porto4200-319 PortoPortugal

Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long *** studies have shown that innate immunity is closely related to the HCC *** effective innate immunity response relies on the tolllike receptors(TLR) found in several different liver cells which,through different ligands and many signaling pathways can elicit,not only a pro-inflammatory but also an oncogenic or anti-oncogenic *** aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic *** performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March ***2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell ***,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced ***3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or ***4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been ***9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more *** polymorphisms in some TLRs have been found and its influence on the risk of HCC has been *** therapeutic targets,TLRs are already in use and have a great *** conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour ***4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been ***2 presents a more ambiguous role,possibly depending on the stag

关键词： Hepatocarcinoma Carcinogenesis Toll-likereceptor Innate immunity Chronic inflammation

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Helical tomotherapy and systemic targeted therapies in solitary plasmacytoma: Pilot study

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World Journal of Radiology 2013年第6期5卷 248-252页

作者： Nadia Wiazzane Cyrus Chargari Corine Plancher Jerome Tamburini Bernard Asselain Alain Fourquet Didier Bouscary Youlia M Kirova Department of Radiation Oncology Institut Curie75005 Paris France Department of biostatistics Institut Curie75005 Paris France Department of Haematology Cochin Hospital75014 Paris France

AIM: To assess the feasibility of the combination of helical tomotherapy(HT) and a concurrent systemic targeted therapy in patients with solitary plasmacytoma (SP) with the aim to decrease toxicity while improving therapeutic efficacy. METHODS: Six patients with biologically, histologically, and radiologically confirmed SP were treated using HT and a systemic targeted treatment concomitantly. Total dose was 40 Gy/20 fractions. Four patients received 4 cycles of concurrent lenalidomide-dexamethasone combination and two patients were treated with concomitant bortezomib-dexamethasone. All toxicities were described using the Common Terminology Criteria for Adverse Effects ***: Five patients had a bone tumor and one patient had an isolated pancreatic mass. Five patients presented with pain, one had neurologic symptoms related to medullary compression, which was treated by an emergency surgery. Median age was 59.5 years (range, 50-74 years). All patients had initial positron emission tomography-computed tomographys, three patients had total body bone magnetic resonance imaging examination, and three patients had computed tomodensitometry scans. The toxicity profile was excellent with no higher than grade 1 toxicity. Four of the six patients experienced a partial radiological response, four had complete response on positions emission tomography and 5/6 patients experienced a complete relief of their symptoms 4 mo after treatment. At a median follow-up of 18 mo, 5/6 patients were controlled clinically, radiologically, and biologically. CONCLUSION: Using HT, we could deliver a highly conformal irradiation concurrently with a molecularly targeted therapy. This association yielded in a high response rate and a low toxicity. A prospective study with longer follow-up will help determining the true benefit of such strategy.

关键词： Plasmacytoma Radiation therapy Targeted treatment Tolerance Lenalidomide Bortezomib

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Ticagrelor inhibits the NLRP3 inflammasome to protect against inflammatory disease independent of the P2Y_(12 ) signaling pathway

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Cellular & Molecular Immunology 2021年第5期18卷 1278-1289页

作者： Bo Huang Yufeng Qian Shujun Xie Xianhua Ye Hanwen Chen Zhifeng Chen Lihuan Zhang Jinming Xu Hu Hu Shenglin Ma Paul Héroux Di Wang Han-Ming Shen Yihua Wu Dajing Xia Department of Toxicology of School of Public Health and Department of Gynecologic Oncology of Women’s HospitalZhejiang University School of MedicineHangzhouChina Department of Cardiology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina Translational Medicine Research Center and Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang ProvinceAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina Department of Thoracic surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Pathology and Pathophysiology Zhejiang University School of MedicineHangzhouChina Department of Oncology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina Department of Epidemiology Biostatistics and Occupational HealthMcGill UniversityMontrealQCCanada Institute of Immunology Zhejiang University School of MedicineHangzhouChina Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Ticagrelor is the first reversibly binding oralP2Y_(12) receptor antagonist to inhibit platelet activation and has been approved by the Food and Drug Administration for the treatment of coronary artery disease. At present, the other pharmacological functions of ticagrelor remain poorly understood. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a critical role in the innate immune system, but its excessive activation also contributes to the pathogenesis of complex diseases. In this study, we systematically examined the effects of ticagrelor on the NLRP3 inflammasome and found that ticagrelor inhibits NLRP3 inflammasome activation in macrophages independent of its classic inhibitory effect on theP2Y_(12) signaling pathway. Further mechanistic studies demonstrate that ticagrelor attenuates the oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC) by blocking chloride efflux, an effect achieved through the degradation of chloride intracellular channel proteins (CLICs) and blockade of the translocation of CLICs to the plasma membrane. Moreover, experiments on lipopolysaccharide-induced sepsis and alum-induced peritonitis in mice confirmed that ticagrelor mitigates the severity of systemic inflammation independent ofP2Y_(12) receptor antagonism. Importantly, oral administration of ticagrelor rapidly and strongly inhibited NLRP3 inflammasome activation in peripheral blood mononuclear cells from patients with acute coronary syndrome. Overall, our study reveals a novel pharmacological function of ticagrelor in addition to its classic antiplatelet properties, which suggests that ticagrelor may serve as a potential therapeutic agent for use in NLRP3-associated diseases.

关键词： Ticagrelor NLRP3 inflammasome P2Y_(12) Chloride efflux ASC

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An Epidemiological Model to Find out Factors Associated with Nodal Involvement among Indian Oral Cancer Patients

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Open Journal of Epidemiology 2018年第3期8卷 117-129页

作者： Vishwajeet Singh SVS Deo Sada Nand Dwivedi Maroof A. Khan Department of biostatistics All India Institute of Medical Sciences New Delhi India Department of Surgical Oncology Dr BRA-IRCH All India Institute of Medical Sciences New Delhi India

In India, the most common cancer among men is cancer of lip-oral and its incidence is further increasing. Nodal metastasis is an important prognostic factor in oral cancer. Previous studies on factors associated with nodal involvement are mainly focused on clinical exploration, and there is very little work in statistical modeling for nodal involvement. Also, the available studies have limited covariates and their varying forms. Further, studies available from India have mainly focused either on occult nodal metastasis only or a specific site of oral or stages. Hence, in order to identify epidemiological determinants of nodal metastasis, objective of this study was to develop a regression model to find out factors associated with nodal involvement and assess its validity. 945 histopathologically proven oral squamous cell carcinoma (OSCC) patients who went under surgery including neck dissection during 1995-2013 at the Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi, India, were included for model building. Another data of 204 patients available during 2014-2015 was used for the temporal validation of the developed model. To assess the factors associated with nodal involvement, stepwise multivariable logistic regression procedure was used and results are presented as odds ratio and corresponding 95% confidence interval (CI). Pain at the time of presentation [1.34 (1.02 to 1.77)], sub mucous fibrosis (SMF) [0.45 (0.21 to 0.95)], palpable neck node [2.38 (1.69 to 3.35)], tongue [1.63 (1.07 to 2.46)] as compared to buccal mucosa and degree of differentiation [1.41 (1.05 to 1.89)] were found to be significantly associated with nodal involvement. Further, diagnostic performance of the developed model was found to be satisfactory on temporal validation. These data suggest that, Pain at time of presentation, presence of clinical neck node, SMF, degree of differentiation and oral site are the most probable factors associated with nodal involvement in OSCC.

关键词： Oral Cancer Oral Squamous Cell Carcinoma Nodal Involvement Metastasis Epidemiological Model

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