tbuckley/cabot-search huggingface dataset:
Relationship between specialty of consulting physician and in-hospital delay, cognitive-behavioral factors and clinical characteristics of myocardial infarction patients with ST elevation
Authors: Yi-wen Xun
Journal: BMJ (2009)

Objective To understand the time of in-hospital delay for percutaneous coronary intervention, different cognitive-behavioral factors, clinical characteristics of the patients admitted with ST-segment elevated myocardial infarction (STEMI) consulted first by physicians with varied specialties.Methods Totally, 308 patients with STEMI admitted to emergency department of 17 hospitals in Beijing within 12 hours after onset with primary percutaneous coronary intervention (PPCI) during November 2005 to December 2007 were observed prospectively by cardiologists and other emergency internists. Demographic data, flow of their consultation at emergency rooms, time of in-hospital delay for PPCI of the patients were collected with structured interviews and medical records by trained interviewers within 72 hours after admission. Multiple logistic regression analysis was performed to identify independent predictors for the in-hospital delay by varied specialty of consulting physician. Results One hundred and ten STEMI patients (35.7%) were consulted first by cardiologists in emergency departments in two of the 17 hospitals, who had a shorter in-hospital delay, with an interval between admission to PPCI of 111 minutes and an interval between undergoing ECG and initiation of PPCI of 45 minutes, significantly shorterthan those consulted first by other physicians in emergency department (121 minutes and 55 minutes, respectively) in other 15 of the 17 hospitals, P<0.01 and P=0.035, respectively. Results of multivariate logistic regression showed that STEMI patients cared for by cardiologists were more likely to have higher educational level (OR=2. 326,P = 0. 033 ), with ever counseling physicians before presenting emergency room (OR = 16. 335, P =0. 023), with Killip score more than two ( OR = 8. 103, P < 0. 01 ) and with typical symptoms (OR=5. 722, P < 0. 01 ) tended to chose cardiologists for consultation. Conclusions Cognitive behavioral factors and clinical characteristics of STEMI patients associated with the specialty of their consulting physicians. Patients cared for by cardiologists had shorter in-hospital delay than those cared for by other physicians in emergency room.

Key words: 
Myocardial infarction ;  Angioplasty;  transluminal;  percutaneous;  coronary; Therapy;  Physicians
Expression of Snail and tumor invasiveness in breast carcionma
Authors: A-li Zhang
Journal: BMJ (2009)

Immunohistochemistry was used to detect the protein expression of Snail in 5 specimens jusxta-eancerous normal breast tissues, 35 specimens of cancerous tissues without metastasis and 20 specimens of breast carcinoma with lymphonode metastasis. Breast carcinoma cell line MDA-MB-231 was transfected with antisense Snail. Results showed that the expression of Snail protein was significantly higher in breast carcinomas than in their normal tissues. The mRNA and protein expressions of Snail in the breast carcinoma cells treated with antisense Snail was significantly decreased while the E-cadherin protein significantly increased (both P < 0.05). The number of invasive ceils treated with antisense Snail was (10.5±1.3)%, while in treated with EGFP was (68.2±2.1)% (P < 0.05). The abnormal expression of Snail contribute to the invasiveness of breast carcinoma. The antisense Snail could prevent the cells ability to invade in vitro, and the effect is related with the up-regulated E-cadherin protein. 

Key words: 
Breast neoplasms;  Snail
Induction chemotherapy with mFOLFOXIRI in cT4N+ locally advanced rectal cancer: Subgroup analysis from a prospective trial.
Authors: Jianwei Zhang, Huabin Hu, Yue Cai, Xiaoyu Xie, Zehua Wu, Jiayu Ling, Yanhong Deng
Journal: Journal of Clinical Oncology (2020)

e16136 Background: FOLFOXIRI had been recommended as induction treatment for patients with T4N+ rectal cancer in the latest NCCN guideline. However, no prospective study to support this recommendation in his population. Here, we tried to analyze the efficacy of FOLFOXIRI as induction chemotherapy in the subgroup of rectal cancer patients with T4N+ from a prospective trial. Methods: A phase II trial exploring the efficacy of mFOLFOXIRI as neoadjuvant chemotherapy in locally advanced rectal cancer had been conducted in our center recently. The subgroups of patients with clinical T4N+ rectal cancer were extracted for further analysis. All candidates were to receive 4 to 6 cycles of mFOLFOXIRI. MRI will be performed every two cycles to assess clinical responses. And then the patients would receive total mesorectal excision directly or proceed to chemoradiotherapy according to the result of restaging evaluation. Postoperative FOLFOX chemotherapy was recommended. The primary endpoint is the ratio of tumor downstaging to ypT0-2N0M0. Results: There were 27 patients with cT4N+. There were twenty male and 7 female, with the median age of 46 years old. MRF involved was observed in 14 patients. Neoadjuvant chemotherapy with mFOLFOXIRI was performed for at least 4 cycles. Six patients received radiotherapy before total mesorectal excision, including short-term radiation in 1 patient. R0 resection was achieved in all the patients (100%) and 24 (88.9%) of patients had received sphincter-saving operation. According to the pathologic result, all patients showed regression in the primary tumor (ypT0-3). The pCR rate was 22.2% (6/27) and the tumor downstaging (ypStage 0-I) rate was 29.6%. Another 13 (48.1%) patients showed downstaging to ypStage II. The main grade 3/4 adverse event was neutropenia (35.7%). With a median follow-up of 25 months, no local recurrence was observed. Only 3 patients developed distant metastasis. The 2-year survival rate for this group of population was 85.0%. Conclusions: mFOLFOXIRI showed high tumor downstaging rate in locally advanced rectal cancer. It could be reasonable to use mFOLFOXIRI as induction chemotherapy for cT4N+ rectal cancer patients. Clinical trial information: NCT02217020 . [Table: see text]
Effect of inhibition of receptor tyrosine kinase AXL by a selective small molecular inhibitor R428 (BGB321) on DNA damage repair response in ovarian cancer cells.
Authors: Ruby Yun-Ju Huang, Xun Hui Yeo, Wai Leong Tam
Journal: Journal of Clinical Oncology (2020)

e15640 Background: AXL is a receptor tyrosine kinase that is often overexpressed in many cancers. It contributes to tumor progression, metastasis and drug resistance through activating downstream signaling cascades, making it an emerging therapeutic target. The first-in-class AXL inhibitor R428 (BGB321) was approved by the FDA for the treatment of relapsed or refractory acute myeloid leukemia. R428 (BGB321) was also reported to show selective sensitivity towards ovarian cancers (OC) with a Mesenchymal (Mes) molecular subtype. Recently, a novel role of AXL in the regulation of DNA damage responses has been described. In this study, we explored further the role of AXL in mediating DNA damage responses by using OC as a disease model. Methods: OC cell lines were treated with R428. Accumulation of γH2AX positive foci was assessed for DNA damage response. Western blotting for γH2AX, ATM and ATR levels were performed. Dose response curves of ATR inhibitors were generated by treating OC cells with the fixed dose of R428 (IC20 concentration of each cell line). Results: AXL inhibition by using R428 resulted in the increase of DNA damage foci in Mes OC cells SKOV3 and HeyA8. This occurred concurrently with the up-regulation of classic DNA damage response signaling molecules such as γH2AX, ATM and ATR. The IC50 of the ATR inhibitor significantly decreased for 2-3 folds in all OC cell lines tested. AXL inhibitor R428 sensitized both BRCA-mutated and non-BRCA-mutated OC cells to a potent and highly selective ATR inhibitor. Conclusions: Our results showed that AXL inhibition rendered cells more sensitive to the inhibition of ATR, a crucial mediator for replication stress, paving ways to the rationale for potential combinatory use of AXL and DNA damage repair inhibitors.
缺血性脑卒中和短暂性脑缺血发作的诊断
Authors: 徐蕾, 龚涛
Journal: BMJ (2012)

《中国急性缺性脑卒中诊治指南2010》中指出,缺血性脑卒巾(ischemic stroke,IS)和短暂性脑缺血发作(transient ischemic attack,TIA)的诊断包括5个步骤,即是否是脑卒中所致的神经功能缺损；脑卒中是否是IS或TIA;IS能否进行溶栓治疗；导致IS或TIA的病因是什么；评估IS或TIA的严重程度、复发风险,安排好康复及二级预防计划。
The G-Quadruplex/Helicase World as a Potential Antiviral Approach Against COVID-19
Authors: Nadia Panera, Alberto Eugenio Tozzi, Anna Alisi
Journal: Drugs (2020)

G-Quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA. G4 sequences/structures have been detected in human and in viral genomes, including Coronaviruses Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2. Here, we outline the existing evidence indicating that G4 ligands and inhibitors of SARS-CoV-2 helicase may exert some antiviral activity reducing viral replication and can represent a potential therapeutic approach to tackle the COVID-19 pandemic due to SARS-CoV-2 infection. We also discuss how repositioning of FDA-approved drugs against helicase activity of other viruses, could represent a rapid strategy to limit deaths associated with COVID-19 pandemic.
Attach importance to diagnosis and management of tinnitus
Authors: Lu He
Journal: BMJ (2016)

耳鸣由于其病因复杂、发病机制不明，一直是临床治疗的难题，然而耳鸣的发病率并不低，可对患者造成严重影响，甚至导致精神心理问题。2014年美国耳鸣临床应用指南颁布以来，推动了业内学者对耳鸣诊治的探讨。文章旨在对国内耳鸣诊疗现状及未来的诊疗趋势进行分析，以期引起我国临床医师对耳鸣诊疗的重视。
Sequencing of treatment matters in synchronous liver or lung only metastatic colon cancer.
Authors: Saurabh Parasramka, Aasems Jacob, Quan Chen, Bin Huang, Zhonglin Hao
Journal: Journal of Clinical Oncology (2020)

4049 Background: Per SEER database, approximately 21% of patients have synchronous metastatic disease at presentation with a median 5 year survival of 14%. Liver is by far the most common site of metastatic disease followed by lung. Metastatectomy of appropriate lesions have achieved a 5 year survival ranged between 40%-70% depending on the extent of the metastasis. For liver or lung only metastatic disease, practice varies from surgery followed by adjuvant chemotherapy to perioperative chemotherapy. Benefit of one approach versus the other has not been demonstrated. We decided to study this using the National Cancer Database (NCDB) database available from the 2010-2015 period. Methods: Adults &gt; 20 years with primary colon cancer (excluding rectal and recto sigmoid junction) with single organ metastatic disease to liver and/or lung at diagnosis were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy in the neoadjuvant setting (NAC) or adjuvant setting (AC) within 1 year of diagnosis. Histology except for adenocarcinoma and variants were excluded. Patients who died within 90 days of surgery were excluded. Descriptive analysis, Kaplan-Meier plots, Log-Rank tests for univariate and proportional hazards models for multivariate survival analyses were performed. To reduce biases, a sensitive analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3175 colon cancer patients with liver or lung only metastatic disease were identified. 2487 (78%) had AC and 688 (22%) had NAC. Approximately 54% were males with 90% less than 75 years of age. More patients had private insurance and were treated in academic centers in the NC group (62 Vs 51%) and (58 Vs 42%) respectively. Both groups had similar Charlson comorbidity index. NC approach had better OS with HR of 0.75 (CI 0.65-0.85; p &lt; 0.0001) on univariate analysis and 0.86 (0.74-0.98; P &lt; 0.0281) on multivariate analysis. On multivariate analysis, age group &gt; 75 years, black race, treatment outside academic research program had worse survival (p &lt; 0.0001, 0.0139, 0.0001) respectively. The sensitive analysis showed the similar effects. Conclusions: Within the limitations of database review, our analysis suggests survival advantage of neoadjuvant chemotherapy approach over surgery first.
Impact of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on overall survival or recurrence free survival in muscle-invasive bladder cancer at cystectomy.
Authors: Scott Dawsey, Iris Yeong- Fung Sheng, Moshe Chaim Ornstein, Wei Wei, Byron H Lee, Omar Y. Mian, Brian I. Rini, Jorge A. Garcia, Timothy D. Gilligan, Shilpa Gupta
Journal: Journal of Clinical Oncology (2020)

e17050 Background: The role of Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) in prognostication of MIBC is not clearly understood. There is growing evidence that, as markers of inflammation, they may have prognostic utility in MIBC at radical cystectomy (RC). Methods: We performed a retrospective analysis of MIBC patients who underwent RC at the Cleveland Clinic from 2/2015 to 1/2018. 84 patients were identified who were either diagnosed with TaN0M0 treated with Neoadjuvant Chemotherapy (NAC) or T1-T4N0M0 disease treated with or without NAC. For NAC, 27 patients received gemcitabine and cisplatin, 2 patients received gemcitabine and carboplatin, 4 patients received unknown regimen, and 3 patients received MVAC. Of the patients, there were 1 with Ta, 34 with T1, 44 with T2, 1 with T3 and 4 with T4 disease. Complete Blood Count with Differential closest to or on the day of resection was used. NLR and PLR were calculated by dividing Absolute Neutrophil Count and Platelet Count by the Absolute Lymphocyte Count, respectively. PLR and NLR were dichotomized at the median. Outcomes were analyzed via Kruskal-Wallis test. Results: Median follow up of patients was 28.8 months. Median NLR and PLR were 15.7 and 263, respectively. Mean NLR and PLR were 18.9 and 310, respectively. NLR and PLR did not correlate with overall survival, recurrence free survival, T or N stage post resection, or pathological response. Females were found to have a higher NLR than males. Conclusions: Contrary to previous reports, our study did not find any prognostic value of NLR and PLR in MIBC patients at RC. Further evaluation of PLR and NLR in MIBC and correlation with molecular features may help understand its potential prognostic role in patients undergoing surgical resection.
甲外血管球瘤10例临床分析
Authors: 梁伟中, 赵作钧, 平小佳, 吕晶, 孙劲文, 周正
Journal: BMJ (2010)

血管球瘤是一种较少见的软组织良性肿瘤,多发生于手部,其中以手指甲下最常见,甲外者很少见.加强对甲外血管球瘤的认识是减少误诊、漏诊的关键.本院自2006年8月至2009年8月共收治甲外血管球瘤10例,总结如下。
Level of moderate-intensity leisure-time physical activity and reduced mortality in middle-aged and elderly Chinese
Authors: Liu Ying, Wen Wanqing, Gao Yu-Tang, Li Hong-Lan, Yang Gong, Xiang Yong-Bing, Shu Xiao-Ou, Zheng Wei, 曹勤, 范竹萍
Journal: BMJ (2018)

背景
很少有研究对亚洲人休闲时间体育锻炼(LTPA)与死亡率的相关性进行前瞻性的评估，而他们比高加索人更容易受到胰岛素抵抗的影响。


方法
对在上海进行的2个大型前瞻性队列研究的数据进行评估。研究对象除外有癌症、冠心病或卒中者，以及在入组3年内死亡的对象。共有男性53 839例、女性66 888例纳入此次研究，他们分别平均被随访9.2年和14.7年。


结果
定期在闲暇时间进行中等强度体育锻炼的人群相对于没有体育锻炼的人群死亡率低，风险比0.86（95%可信区间：0.80~0.93），甚至那些锻炼强度远低于当前运动指南所推荐的最低程度（每周运动150分钟或者达到7.5个代谢当量小时）的人群死亡率也降低。中等强度运动与死亡率之间的关系，在LTPA达到指南推荐的最低程度的3~5倍前呈剂量反应关系。同时也观察到由心血管疾病、癌症或其他原因导致的死亡率也有类似的关联。


结论
定期参加中等强度LTPA能够降低死亡率，尤其是降低心血管疾病的死亡率，即使LTPA低于目前指南所推荐的最低水平。增加中等强度LTPA的运动量，达到指南推荐的最低水平的3~5倍，可以进一步降低潜在的风险。
Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial
Authors: Chunyan Lan, Jingxian Shen, Yin Wang, Jundong Li, Zhimin Liu, Mian He, Xinping Cao, Jiayu Ling, Jiaming Huang, Min Zheng, Guorong Zou, Haowen Yan, Qing Liu, Fan Yang, Wei Wei, Yanhong Deng, Ying Xiong, Xin Huang
Journal: Journal of Clinical Oncology (2020)

Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer.
心肌致密化不全致窦性停搏二例
Authors: 张兆奎, 张天德, 张震甫, 杨万胜, 崔雪莲, 马菊兰, 叶俊玲
Journal: BMJ (2009)

例1 患者男性,40岁,因劳累出现心悸,头晕伴全身乏力1 h于2008年8月20日入院.无胸痛气短、黑朦及晕厥.患者自幼心跳缓慢,20年前曾因头晕考虑先天性心脏病,但未予诊治.体检:血压130/80 mm Hg(17.3/10.6 kPa),神志清楚,颈静脉无怒张,两肺呼吸音清,心界向左扩大,心率48移/min,节律不齐,胸骨左缘3～4肋间可闻及2/6级收缩期杂音,余无异常。
Effect of early integration of specialized palliative care into standard oncologic treatment on the quality of life of patients with advanced head and neck cancers: A phase III randomized controlled trial.
Authors: Pankaj Singhai, Vijay Maruti Patil, Mary Ann Muckaden, Jayita Deodhar, Naveen Salins, Vanita Noronha, Amit Joshi, Nandini Sharrel Menon, Ashwini Khake, Sachin Babanrao Dhumal, Kumar Prabhash
Journal: Journal of Clinical Oncology (2020)

12013 Background: Early palliative care is an important aspect of palliative treatment but has never been evaluated in head and neck cancer. Hence we performed this study. Methods: This was an open-label phase 3 randomised study which enrolled adult patients with squamous cell carcinoma of the head and neck region which warranted palliative systemic therapy. They were 1:1 allocated to either systemic therapy with (EPC arm) or without the addition of early palliative care service (STD arm). Patients were administered the Edmonton Symptom Assessment Scale (ESAS-r) and FACIT HN questionnaire at baseline and 4 weekly thereafter for 12 weeks. The primary endpoint was change in the quality of life (QOL) measured using FACIT HN 12 weeks after randomization. The secondary endpoints were changed in symptom burden at 12 weeks in ESAS-r and overall survival. A repeated-measures analysis of covariance (ANCOVA) was performed to examine the effects of arm and stratum on change in QOL (or symptom score), after controlling for baseline score. Results: Ninety patients were randomised in each arm between 1st June 2016 to 14th August 2017. The compliance with the questionnaires was 100% at baseline. In EPC arm the 70 patients were alive at 3 months and 67 (95.7%) completed the FACIT HN and 64 (91.4%) completed ESAS-r questionnaires. While in the STD arm out of 69 alive the corresponding figures were 61(88.4%) and 59 (85.5%) respectively. There was no statistical difference in change in QOL scores and ΔESAS-r at 12 weeks between the 2 arms (Table). The median overall survival was similar between the 2 arms. (Hazard ratio for death-1.006 (95%CI 0.7347-1.346)). Conclusion: In this phase 3 study, integration of early palliative care in head and neck cancer patients did not result in improvement in the quality of life scores, symptom scores or overall survival. Clinical trial information: CTRI/2016/03/006693 . [Table: see text]
世界卫生组织和世界家庭医生组织加强基层医疗保健的新策略
Authors: 李国栋
Journal: BMJ (2009)

世界卫生组织(World Health Organization,WHO)是联合国制度下的国际医疗机关,由WHO总干事率领,制订卫生指引及标准,协助各国实施公共卫生政策.世界家庭医生组织(WONCA)由世界全科医生/家庭医生国立学院、大学和学会组织组成,成立于1972年,有119个成员组织遍布99个国家,超过25万个家庭医生,是与WHO有官方联系的非政府组织之一,被公认为非政府家庭医学组织的代表.这奠定了家庭医学在全球医疗中的重要性,并肯定了WONCA作为全球家庭医学标准厘定、教育、培训、研究的国际领导者角色,也肯定了WONCA在全球各地提倡家庭医生在基层医疗中的角色地位。
Treatment of early‐stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study*
Authors: P. Quaglino, H.M. Prince, R. Cowan, M. Vermeer, E. Papadavid, M. Bagot, O. Servitjie, E. Berti, E. Guenova, R. Stadler, C. Querfeld, A.M. Busschots, E. Hodak, A. Patsatsi, J. Sanches, M. Maule, J. Yoo, M. Kevin, P. Fava, S. Ribero, L. Zocchi, M. Rubatto, M.T. Fierro, U. Wehkamp, M. Marshalko, C. Mitteldorf, O. Akilov, P. Ortiz‐Romero, T. Estrach, L. Vakeva, P.A. Enz, M. Wobser, M. Bayne, C. Jonak, M. Rubeta, A. Forbes, A. Bates, M. Battistella, R. Amel‐Kashipaz, B. Vydianath, A. Combalia, E. Georgiou, E. Hauben, E.K. Hong, M. Jost, R. Knobler, I. Amitay‐Laish, D. Miyashiro, J. Cury‐Martins, X. Martinez, C. Muniesa, H. Prag‐Naveh, A. Stratigos, V. Nikolaou, K. Quint, C. Ram‐Wolff, K. Rieger, R. Stranzenbach, Á. Szepesi, S. Alberti‐Violetti, E. Felicity, L. Cerroni, W. Kempf, S. Whittaker, R. Willemze, Y. Kim, J.J. Scarisbrick
Journal: British Journal of Dermatology (2020)

The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF).
Tumor methylation patterns to measure tumor fraction in cell-free DNA.
Authors: Colin Melton, Pranav Singh, Oliver Venn, Earl Hubbell, Samuel Gross, Yasushi Saito, Joshua Newman, Lily Zhang, Christopher Chang, Gordon Cann, Matthew H. Larson, Sarah Stuart, Vasiliki Demas, Alexander Aravanis, Arash Jamshidi
Journal: Journal of Clinical Oncology (2020)

3052 Background: Cell-free DNA (cfDNA) tumor fraction (TF), the proportion of tumor molecules in a cfDNA sample, is a direct measurement of signal for cfDNA cancer applications. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) is a prospective, multi-center, observational, case-control study designed to support development of a methylation-based, multi-cancer detection test in which a classifier is trained to distinguish cancer from non-cancer. Here we leveraged CCGA data to examine the relationship between cfDNA containing tumor DNA methylation patterns, TF, and cancer classification performance. Methods: The CCGA classifier was trained on whole-genome bisulfite sequencing (WGBS) and targeted methylation (TM) sequencing data to detect cancer versus non-cancer. 822 samples had biopsy WGBS performed; of those, 231 also had cfDNA targeted methylation (TM) and cfDNA whole-genome sequencing (WGS). Biopsy WGBS identified somatic single nucleotide variants (SNV) and methylation variants (MV; defined as methylation patterns in sequenced DNA fragments observed commonly in biopsy but rarely [ &lt; 1/10,000] in the cfDNA of non-cancer controls [n = 898]). Observed tumor fragment counts (SNV in WGS; MV in TM), were modeled as a Poisson process with rate dependent on TF. TF and classifier limits of detection (LOD) were each assessed using Bayesian logistic regression. Results: Across biopsy samples, a median of 2,635 MV was distributed across the genome, with a median of 86.8% shared with ≥1 participant, and a median of 69.3% targeted by the TM assay. TF LOD from MV was 0.00050 (95% credible interval [CI]: 0.00041 - 0.00061); MV and SNV estimates were concordant (Spearman’s Rho: 0.820). MV TF estimates explained classifier performance (Spearman’s Rho: 0.856) and allowed determination of the classifier LOD (0.00082 [95% CI: 0.00057 - 0.00115]). Conclusions: These data demonstrate the existence of methylation patterns in tumor-derived cfDNA fragments that are rarely found in individuals without cancer; their abundance directly measured TF, and was a major factor influencing classification performance. Finally, the low classifier LOD (~0.1%) motivates further clinical development of a methylation-based assay for cancer detection. Clinical trial information: NCT02889978 .