bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automate incidental findings in radiology reports using natural language processing and machine learning to identify and classify lung nodules.
Authors: French Christi , Kurbegov Dax , Spigel David R. , Makowski Maciek , Terker Samantha , Clark Paul Alexander 
Published: October 2019

49 Background: Pulmonary nodule incidental findings challenge providers to balance resource efficiency and high clinical quality. Incidental findings tend to be under evaluated with studies reporting appropriate follow-up rates as low as 29%. The efficient identification of patients with high risk nodules is foundational to ensuring appropriate follow-up and requires the clinical reading and classification of radiology reports. We tested the feasibility of automating this process with natural language processing (NLP) and machine learning (ML). Methods: In cooperation with Sarah Cannon, the Cancer Institute of HCA Healthcare, we conducted a series of experiments on 8,879 free-text, narrative CT radiology reports. A representative sample of health system ED, IP, and OP reports dated from Dec 2015 - April 2017 were divided into a development set for model training and validation, and a test set to evaluate model performance. A “Nodule Model” was trained to detect the reported presence of a pulmonary nodule and a rules-based “Size Model” was developed to extract the size of the nodule in mms. Reports were bucketed into three prediction groups: ≥ 6 mm, <6 mm, and no size indicated. Nodules were placed in a queue for follow-up if the nodule was predicted ≥ 6 mm, or if the nodule had no size indicated and the report contained the word “mass.” The Fleischner Society Guidelines and clinical review informed these definitions. Results: Precision and recall metrics were calculated for multiple model thresholds. A threshold was selected based on the validation set calculations and a success criterion of 90% queue precision was selected to minimize false positives. On the test dataset, the F1 measure of the entire pipeline was 72.9%, recall was 60.3%, and queue precision was 90.2%, exceeding success criteria. Conclusions: The experiments demonstrate the feasibility of technology to automate the detection and classification of pulmonary nodule incidental findings in radiology reports. This approach promises to improve healthcare quality by increasing the rate of appropriate lung nodule incidental finding follow-up and treatment without excessive labor or risking overutilization.
Multidimensional integrative medicine applied to outpatient cancer treatment in southern Brazil: Preliminary cost-effectiveness analysis.
Authors: Fleck James Freitas , Preger Ricardo , Venegas Luis Fernando , Trasel Henrique de Araujo Vianna 
Published: October 2019

5 Background: Cost-effective analysis as part of cancer treatment decision-making. Methods: We reviewed deaths of 52 metastatic cancer patients treated with multidimensional integrative medicine (MIM) approach. Patients received standard oncologic treatment plus a MIM predefined program of emotional, cognitive and social support. The method included empathy improvement, changes on physician attitude and office environment, modulation of staff behavior supporting patient’s needs and rights, promotion of belongingness, increasing on patient’s protagonism using multimedia interactive narrative and shared decision-making. Patients were categorised according to the tumor site, pathologic, molecular and IHC characteristics, clinical stage and treatment. Observed survival was defined as the time elapsed between the detection of first metastasis and death. The observed survival for each patient was compared with the median expected survival previously reported on prospective randomised trials which had accrued patients with similar prognostic factors based on a best fit model. Treatment monthly cost for each patient was converted in American dollars (USD) on a daily exchange basis. Cost of the treatment periods were compared with those analysed in four large USA commercial managed care plans. Results: Treatment of metastatic cancer patients using MIM showed a 44% increase in median survival and a 48% decrease in cost. The estimated ICER/QALY was of 32304 USD, which represented 2.0 of Brazilian PPP. Conclusions: Despite methodological limitations, this is the first study to indicate a cost-effective survival increase in metastatic cancer patients using a MIM-behavioral modulation model. [Table: see text]
AI for early-stage breast cancer screening.
Authors: Manjunath Geetha , Madhu Himanshu , Kakileti Sivateja 
Published: October 2019

50 Background: In emerging markets, a routine mammogram is not feasible due to cost, accessibility and lack of skilled technicians. It is also not effective in women with dense breasts. We explore an alternative modality based on Artificial Intelligence over thermal images for early detection of breast cancer. Infrared imaging is a non-contact, radiation-free technique that detects breast abnormalities based on thermal changes in the body seen due to increased vascularity and metabolic activity of the tumour. Thermography is only approved as an adjunct modality by US FDA, as manual interpretation of thermal images is error prone and subjective. We have developed an AI- based software (called Thermalytix) for automatic analysis of Thermal images using machine learning to extract and analyse abnormal patterns based on thermal distribution, asymmetry and vascular structure; to identify malignancy in symptomatic and asymptomatic subjects. Methods: We compare performance of Thermalytix with Mammography on a total of 769 subjects who walked into 3 sites for mammography screening. Subjects were sent for NIRAMAI screening prior to other tests (mammography or sonomammography). Pregnant women, lactating mothers and cancer survivors were excluded from the study. 534 subjects had either lump or nipple discharge as a symptom and 235 subjects did not have any symptoms. Mammography was conducted on 407 subjects and rest went through sonomammography as per the discretion of radiologist. Results: Sensitivity of Thermalytix was 92% in symptomatic women with a specificity of 71.9%; while 100% sensitivity and 92.9% specificity was found in women without any symptoms. Mammography, on the other hand, presented 91% sensitivity and 70.7% specificity in symptomatic women. In asymptomatic women, mammography however showed 67% sensitivity and 98.9% specificity. Conclusions: Thermalytix was found to be a promising screening and diagnostic tool while mammography worked better as a diagnostic tool. [Table: see text]
Immune dysregulation underpins radioresistance in nasopharyngeal carcinoma (NPC).
Authors: Wang Hai-Tao , Yeo Eugenia Li Ling , Hwang Jacqueline Seok Gek , Tan Gek San , Ong Enya Hui Wen , Low Kar Perng , Chimmiri Anusha , Woo Wai Yee , Nei Wen Long , Lim Kiat Hon , Tan Michael Chien Sheng , Loh Josh Jie Hua , Teo Constance Ee Hoon , Heah Harold Hon Wei , Tay Gerald Ci An , Wee Joseph , Iyer N Gopalakrishna , Sun Ying , Bei Jin-Xin , Chua Melvin L.K. 
Published: October 2019

52 Background: Radiotherapy (RT) is a primary modality in the treatment of NPC. However, 30% of patients present with disease recurrence following RT of this radiosensitive tumor. Here, we investigated the molecular and immune profiles associated with radioresistant (RR) NPC. Additionally, we investigated for aberrant molecular pathways in paired recurrences of patients to uncover new drivers underpinning radioresistance. Methods: We prospectively recruited a cohort of 100 NPC patients who completed definitive RT/chemoRT; including 30 cases who were recruited at recurrence. Whole exome sequencing (WES) at 200x was performed to identify low frequencies ( < 1%) of true somatic nucleotide variants (SNVs) and copy number alterations (CNAs). Transcriptomic profiles from RNAseq were interrogated using supervised and unsupervised statistical approaches to determine aberrant pathways that were significantly associated with RR. Results: Genomic instabilityas characterized by percentage genome alteration (PGA) was comparable in our cohort. Additionally, we did not observe any common or exclusive CNAs between RR- and nr-NPC cases. Based on a constellation of immune-related signatures, we observed an “immune-cold” profile that is associated with RR-NPC compared to nr-NPC controls, which is characterized by low expression of CD8+ T cell infiltration and interferon-γ response. Expectedly, pathways relating to angiogenesis, hypoxia and NOTCH signaling were upregulated in the RR-NPC cohort. Interestingly, we observed a reversal of the immune phenotype from “cold” to an enrichment of effector T cell infiltration in the paired recurrences. Conclusions: Here, we present a comprehensive mutational landscape of RR-NPC, which revealed the potential role of the immune environment in modulating RR. The longitudinal immune dysregulation of the tumor microenvironment between the de novo tumors and recurrences could be a driver or passenger event during the onset of recurrence.
Clinical utility of CDH17 biomarker in tumor tissues and liquid biopsies for detection and prognostic staging of colorectal cancer (CRC).
Authors: Tsoi Helen , Wong Kwong-Fai , Luk John M. , Staunton Don 
Published: October 2019

53 Background: Cancer surveillance using blood-based biomarker tests allows for early cancer detection and more effective prompt treatment. Immunohistochemical staining of tumor-specific antigens can also provide valuable prognostic information and contribute to the design of treatment strategy. Our early studies and work from other investigators have identified cadherin-17 (CDH17) as a promising biomarker in both tumor tissues and liquid biopsies. CDH17 overexpression in cancer tissue was found predictive of poor prognosis in patients with gastric cancer, hepatocellular carcinoma and ovarian cancer. Plasma CDH17 was elevated in patients with gastric cancer when compared to healthy subjects. However, despite the diagnostic and prognostic value of CDH17, robust and accurate assays for CDH17 detection in liquid and tumor biopsies have yet to be developed. Methods: In order to establish CDH17 immunoassays, we have first generated a proprietary library of more than 300 antibodies against CDH17, and from this library, isolated a panel of monoclonal antibodies (mAbs) exhibiting specific and high-affinity binding to the different extracellular domains of CDH17. Results: The immunohistochemical staining of CRC tissues with one of our mAbs revealed a stepwise increase in CDH17 with the progression of cancer from early to late CRC. A sandwich-ELISA was also developed to show significantly elevated plasma CDH17 in patients with CRC when compared to healthy individuals. Like CDH17 expression in CRC tissues, plasma CDH17 also showed a gradual increase with progression to more advanced stages of CRC. The newly developed ELISA also demonstrated that the number of CDH17-containing exosomes was significantly higher in blood isolated from patients with CRC. Notably, our mAbs could also enumerate CDH17-positive circulating tumor cells (CTCs), of which the level was associated with tumor stage. Conclusions: All these findings clearly indicate the clinical utility of CDH17 in tumor tissues and liquid biopsies for detection and prognostic staging of CRC. Further validation of our proprietary CDH17 immunoassays are being conducted in multiple independent CRC cohorts.
Identification of sentinel lymph nodes using contrast-enhanced ultrasound in breast cancer patients who underwent neoadjuvant chemotherapy.
Authors: Wu Xiufeng , Tang Lina , Zeng Yi , Chen Xia 
Published: October 2019

59 Background: The aim of this prospective study was to evaluate the feasibility of contrast-enhanced ultrasonography (CEUS) for the identification of sentinel lymph node (SLN) in breast cancer patients with cN0 following neoadjuvant chemotherapy (NAC). Methods: Patients with cN0 following NAC (n=66) received a periareolar injection of SonoVue followed by ultrasound (US) to identify contrast-enhanced SLN before surgery. All patients underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. The identification rate, sensitivity, specificity, accuracy, false negative rate, negative predictive value, positive predictive value was recorded. Results: In almost all cases, the SLNs were easily identified with an identification rate of 98.5 % (65/66). Compared with pathological diagnosis, sensitivity, specificity, accuracy, and false negative rate of CEUS for SLN diagnosis were 66.7%, 95.8%, 78.8%, and 14.3% respectively. Conclusions: Identification of SLN by CEUS is a technically feasible method with an identification rate as high as 98.5%. [Table: see text][Table: see text]
Prognostic implication of forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) in epithelial ovarian cancer.
Authors: Cho Hanbyoul , Han Gwan Hee , Kim Jae-Hoon 
Published: October 2019

61 Background: Transcriptional factor, Forkhead box protein O1 (FOXO1) has been reported to play an imported role in human cancer, but the role in epithelial ovarian cancer (EOC) has not yet been clarified. Here, we evaluatedthe expression and clinical significance of FOXO1 in EOC. Methods: Immunohistochemical analyses of FOXO1 and PAX3 in 212 in EOCs, 57 borderline ovarian tumors and 153 benign epithelial ovarian tumors and 79 nonadjacent normal epithelial tissues were performed using tissue microarray analysis. The data were compared with clinicopathological variables including the survival of EOC patients. Also, the effect of FOXO1 on cell growth were assessed in EOC cell lines. Results: The expressions of FOXO1 and PAX3 protein were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues and borderline tumors respectively (all p< 0.001). Overexpression of FOXO1 was significantly associated with poor grade ( p = 0.004). FOXO1 expression showed trend of positive correlation with that of PAX3 in EOC tissues ( Spearman’s rho0.118, p= 0.149). Multivariate survival analysis revealed that the high expression of FOXO1 (hazard ratio = 2.74 [95% CI, 1.22–13.10], p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed high hazard ratio (hazard ratio = 5.53 [95% CI, 2.47–12.40], p< 0.001) for overall survival. In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability and migration. Conclusions: This study reveals that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results not only suggest the promising potential of FOXO1 and PAX3 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and PAX3 of EOC.
Clinical factors associated with comprehensive genomic variation profiling of cervical cancer.
Authors: Xu Qin , Lin Yibin , Lin Xian , Liu Jing , Li Li , Zheng Peng , Liu Bin , Shi Huaijing 
Published: October 2019

62 Background: To better understand the mechanism contributing to cervical carcinogenesis, we perform a comprehensive analysis of genomic alterations in cervical cancer (CC). Methods: We conducted whole-exome sequencing of 43 CCs and established strict integrated workflow of genomic analysis. Correlation analysis was performed to measure the relationships between gene mutations and clinical characteristics of CC patients. Results: Genomic analysis revealed 28 genes frequently mutated in CC including BRD4 (4/43), AXL (4/43), MED12 (4/43), which are undetermined genomic features in CC, and identified recurrent genetic mutations in PIK3CA (16/43), KMT2D (11/43), KMT2C (6/43), FBXW7 (5/43), FAT1 (5/43), ERBB2 (4/43), EP300 (3/43) and NFE2L2 (3/43). Intriguingly, CC patients harbored high frequent mutations in BRCA2 (7/43), but not in BRCA1. The relationship between BRCA2 mutations and clinical factors is yet to be determined. The identified mutations predominately resulted in the dysregulation of the PI3K/AKT/mTOR pathway. Interestingly, we found that AXL mutations were positively correlated with FIGO stage ( P = 0.028), regional lymph node metastasis ( P = 0.011) and distant metastasis ( P = 0.022). KMT2C mutations were positively correlated with FIGO stage ( P = 0.004) and distant metastasis ( P = 0.009). SF3B1 mutations were positively correlated with regional lymph node metastasis ( P = 0.027) and distant metastasis ( P< 0.001). NFE2L2, ERBB2, RAC1, MED12, MET, BAP1, PTPRD and HNF1Amutations were positively correlated with distant metastasis ( P = 0.045, P = 0.004, P = 0.022, P = 0.001, P< 0.001, P< 0.001, P = 0.014, P< 0.001, respectively). POLD1 mutations were positively associated with regional lymph node metastasis ( P = 0.029). However, NOTCH1 mutations were negatively associated with regional lymph node metastasis ( P = 0.047). STK11 mutations were negatively associated with FIGO stage ( P = 0.013). Conclusions: Our results highlight the application of deep sequencing for understanding the molecular mechanisms and uncovering potential diagnostic and therapeutic targets of CC.
Clinical actionability of universal sequencing for germline cancer susceptibility gene mutations among patients with colorectal cancer: A prospective study.
Authors: Jiang Wu , Ding Peirong 
Published: October 2019

63 Background: Genetic predisposition is an important cause of colorectal cancer (CRC). Previous studies have demonstrated that universal sequencing in unselected CRC patients with multi-gene panel could detect more hereditary cancer syndromes. However, it is unclear whether this strategy would change clinical management for the affected individuals. Methods: We prospectively enrolled a consecutive cohort of 486 CRC patients, comprising of unselective patients aged no more than 70 years and patients older than 70 years with hereditary risk features. All participants received germline testing using a comprehensive panel of 81 genes associated with various hereditary cancer syndromes. Results: Fifty-two pathogenic or likely pathogenic mutations were discovered in 51 (10.5%, 51/486) patients, including 20 (4.1%) Lynch syndrome, 11 (4.1%) germline mutations with known CRC risk, and 20 (4.1%) in other cancer susceptibility genes not traditionally associated with CRC. Among them, 21 (4.3%) mutation-positive patients would have been left undiagnosed if they only adhered to present guidelines. Nearly seventy percent (36/51) of the mutation-positive patients were found to carry clinicalactionable germline mutations, for whom enhanced screening and/or tailored treatment was recommended.CRC location, multiple CRC diagnoses, personal history of malignancy, or family history of malignancy was not significantly related to the presence of a mutation in non-CRC susceptibility genes. Conclusions: Universal germline sequencing for cancer susceptibility gene among CRC patients substantially identified more individuals with hereditary cancer syndrome and actionable germline mutations, and these patients might benefit from enhanced surveillance and better tailored treatment. Clinical trial information: NCT03365986.
Metformin, aspirin and statin and risk of cancer: A population-based study in Thailand.
Authors: Oranratnachai Songporn , Thongmung Nisakorn , Phetchoo Piyaporn , Rattanasiri Sasivimol , Thakkinstian Ammarin , Lukerak Somthawin , Vathesatogkit Prin , Trachu Narumol , Sritara Piyamitr , Sirachainan Ekaphop , Reungwetwatttana Thanyanan 
Published: October 2019

65 Background: There were the conflicted results of the association of ASA, metformin or statin and risk of cancer in the previous studies. This is a population-based study in Thai population which aims to investigate the association between these drugs and the risk of cancer. Methods: A population-based retrospective study was done in Electricity Generating Authority of Thailand (EGAT) 1 and 2 databases which have been contained the 27-year and 15-year follow-up time, respectively. This database composed of the clinical characteristics, onset of cancer, and history of interested drugs from the questionnaire, together with the laboratory result from January 2002 to December 2015. We adjusted for age, sex, BMI, smoking and alcohol consumption. The incidence rate ratio (IRR) was estimated for the association between incidence of cancer and interested drugs. Results: Among 2508 and 2731 participants in EGAT1 and 2 respectively, the incidence of cancer was 8.3% in EGAT 1 and 3.5% in EGAT 2. From univariate analysis, use of interested drugs was significant associated with increased risk of cancer with IRR 1.74 ( P< 0.001) for ASA, IRR 1.54 ( P= 0.043) for metformin and IRR 1.64 ( P= 0.001) for statin. In multivariate analysis, only ASA showed significant increasing risk of cancer with IRR 1.47 ( P= 0.021). There was a trend increasing risk of cancer for metformin and statin users but not significant. Older age, low BMI, and female significantly associated with higher risk of cancer. In sub-group analysis, age and alcohol were significantly increased risk of GI cancer, while ASA use showed a non-significant trend of increasing risk of GI cancer. HBV infection was a strongly risk factor for hepatobiliary cancer and statin use had a trend lowering risk of this cancer but it was not statistically significant. Metformin also showed a non-significant trend of increasing risk of thoracic cancer. Conclusions: ASA use significantly associated with increasing risk of cancer but metformin and statin showed a trend of higher risk of cancer. These drugs may associate with cancer metabolome pathway which maybe an important role of carcinogenesis. However, ASA, metformin or statin use and risk of cancer is needed to confirm in the longer follow-up and larger cohort.
Single nucleotide polymorphism within gene in NFKBIA is associated with the risks of nasopharyngeal carcinoma in Chinese Han population.
Authors: Zhang Hanyi , Lu Shun , Sun Chang , Deng Siyao , Lang Jin Yi 
Published: October 2019

67 Background: Nasopharyngeal Carcinoma(NPC) is an Epstein-Barr virus(EBV) associated malignancy with remarkable ethnic and geographical distribution. The EBV oncoprotein latent membrane protein 1 (LMP1) is the primary oncogene of EBV infection through the its signaling cascade and its connections to other pathways including NF-κB, TGF-β and JNK signaling, which plays an important role in the pathogenesis of NPC. In GWASs (Genome-wide association studies) associations these pathways were also identified. Single nucleotide polymorphisms (SNPs) in the regulatory regions may regulate the expression of genes in these pathways, or affect the function of the coded protein. Methods: Altogether 149 SNPs were covered by the 15 SNPs in the TRAF2, TRAF3, NFKBIA, MAP2K4, and CHUK genes were genotyped in a hospital-based case-control study of 350 NPC cases and 587 healthy controls from the Chinese Han. The observed genotype frequencies in the controls were tested for Hardy–Weinberg equilibrium (HWE) using the chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between genotypes and NPC risk and tumor characteristics were calculated by logistic regression, and they were adjusted for multiple testing using the SNP spectral deposition (SNPSpD) approach for multilocus analyses. Results: We found one NFKBIA SNP was associated with NPC risk after adjustment for multiple comparisons. Minor allele carriers of the NFKBIA had an increased risk of NPC (P 0.05). The analyses were adjusted for age and gender. For a polymorphism with a variant allele frequency between 10 %and 50%, the study had greater than 90% power to detect an OR of 1.50 at a significance level of 0.05 (PS—software for power and sample size calculation, http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize). The other genotyped SNPs that we found were not associated with NPC risk. Conclusions: Our data suggests that genetic variation especially in the NFKBIA maybe a useful biomarker for NPC screening and further studies are warranted.