tbuckley/cabot-search huggingface dataset:
The development and validation of a novel targeted methylation sequencing technology detecting 0.003 percent tumor signal in early-stage cancer plasma.
Authors: Grace Q. Zhao, Yun Bao, Heng Wang, Jianmin Wang, Shengrong Lin
Journal: Journal of Clinical Oncology (2020)

4092 Background: Methylation analysis in cell-free DNA holds great potential for early cancer detection. In the plasma of early stage cancer patient, the tumor content is estimated to be less than 0.1%, therefore demands a highly sensitive assay. Targeted Methylation Sequencing (TMS) is the most promising approach; however, the current sensitivity and specificity are compromised by low efficiency and low recovery of target enrichment, and further hampered by background noise associated with large panels. The ideal solution would be an in-depth analysis using a focused small cancer-specific methylation biomarker panel, but is not supported by existing technologies. Methods: Here we present a new technology designed for TMS analysis in cfDNA: Point-n-Seq, featuring an enrichment of target molecules directly from cfDNA before bisulfite conversion and amplification. Particularly, this technology enables small focused panel that interrogates the methylation status of 1 to ~1000 markers. We designed a CRC panel covering 100 methylation markers in 3 steps: identify ~1000 CRC-specific markers from public databases; eliminate makers with high background signal in baseline cfDNA of healthy population; finalize the list with the most differentiating markers between patient and healthy cfDNA. Results: The capture of Point-n-Seq CRC panel is highly efficient resulting in high uniformity (94% &gt; 0.5X) and on-target rate ( &gt; 80%). For 20 ng cfDNA input, more than 1000 deduped informative reads were obtained for each marker on average, despite the high GC content ( &gt; 80%). The output of informative reads was linear to the cfDNA input ranging from 1 ng to 40 ng. In titration studies, 0.6 pg (0.2X genome equivalent) methylated DNA in 20 ng cfDNA (0.003%) was reliably detected over cfDNA background. Using plasma samples from patients with CRC - early stage (I, n = 7; II, n = 7), late stage (III, n = 11; IV, n = 3), and control individuals (n = 105), the average fractions of methylated signal are 0.0034%, 0.013%, 0.09%, 0.17%, 0.29% for control, stage I, II, III, IV accordingly. With a simple cut-off using methylation fraction, Point-n Seq CRC panel achieved a sensitivity of 86% for stage I, 100% for stage (II-IV) at a specificity of 91%, with AUC = 0.96. Conclusions: Point-n-Seq TMS is the first hybridization based NGS technology enables the small focused methylation panel (e.g. 100 markers) sequencing using cfDNA, and it will greatly facilitate the development of practical and cost-effective methylation assays for clinical use.
肺癌颞骨转移致周围性面瘫一例
Authors: 李玉洁
Journal: BMJ (2010)

患者女,61岁.无明显诱因右耳鸣、面瘫、听力下降、持续右侧胸痛1个月,于2010年2月4日来我院就诊.1个月前在当地社区医院按Bell's面瘫治疗无效,患者既往身体健康,无耳痛和流脓,不伴有眩晕,也无咳嗽、咳痰和咯血。
Effectiveness of PD-L1 inhibitors in metastatic or recurrent squamous cell carcinoma of head and neck: An observational, indirect comparison.
Authors: Michel Bila, Paul M. Clement, Jeroen Van Dessel
Journal: Journal of Clinical Oncology (2020)

e18503 Background: The prognosis for recurrent or metastatic Squamous Cell Carcinoma of Head and Neck (HNSCC) remains dismal and its treatment poses a challenge for oncologists. Agents against programmed cell death ligand 1 (PD-L1) have shown beneficial effects on overall survival (OS) for HNSCC. The aim of the present study was to compare differential effects of PD-L1 inhibitors on recurrent and metastatic HNSCC. Methods: In an indirect comparison of patients with recurrent HNSCC were matched to patients with metastatic HNSCC. All patients were treated with PD-L1 inhibitors at the general medical oncology department of UZ Leuven. Kaplan-Meier methods and Cox regression models were used to calculate the overall survival. Results: From December 2013 to July 2019, 68 patients with metastatic and 59 with recurrent HNSCC were enrolled and evaluable. A significant difference in OS was found between recurrent and metastatic groups (p &lt; 0.02). The mean OS was 7.6 months (95% CI: 2.4-11.3 months) for the recurrent group, while in the metastatic group the mean OS was 13.7 months (95% CI: 5.7-16 months). Conclusions: As a second-line therapy, PD-L1 inhibitors were associated with longer overall survival in metastatic compared to recurrent HNSCC.
Polystictus glycopeptide capsules plus photodynamic therapy for male urethral condyloma acuminatum: clinical observations and gene detection
Authors: Weiguo Sun, Ming Jiang, Xiaoning Liu
Journal: BMJ (2014)

A total of 26 male patients with urethral condyloma acuminatum took Polystictus glycopeptide capsules orally for 4 weeks plus 1-5 sessions of photodynamic therapy. Prior to the first session, human papilloma virus (HPV) genotype of wart tissue was detected. Verrucous body fell off completely. The follow-up period was 6 months. There was one recurrent case. And 24 cases had HPV genotype DNA. The positive rate of high-risk infection was 46.2%; the high/low-risk mixed type cross infection was present. The multiple HPV6 low-risk infection rate was 23.1% and multiple high-risk infection rate 58.3%; high-risk type HPV16, HPV31, HPV58 and HPV6, HPV11 were all of mixed types.


Key words: 
Condyloma acuminatum; HPV genotype
Adjuvant chemotherapy with or without an anthracycline in older adults with node-negative triple-negative breast cancer (TNBC): A SEER Medicare study.
Authors: Anna R Schreiber, Jodi Kagihara, Megan Eguchi, Peter Kabos, Elisabeth Meyer, Lavanya Kondapalli, Christine M. Fisher, Cathy J Bradley, Jennifer Robinson Diamond
Journal: Journal of Clinical Oncology (2020)

e12505 Background: TNBC is an aggressive breast cancer subtype comprising approximately 15% of breast cancers. Adjuvant chemotherapy reduces the risk of recurrence, particularly in patients with tumors &gt; 1 cm or node positive disease. Anthracycline (A) + taxane (T)-containing regimens are more efficacious than T-based regimens, however, the risk of cardiac toxicity is greater in older patients. We investigated the use of AT and T-containing regimens in patients ≥ 66 years old with node negative TNBC and evaluated clinical outcomes and cardiac risk factors. Methods: We identified female patients ≥ 66 diagnosed between 2010-2015 with TNBC node negative disease in the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Baseline characteristics, including age, tumor size, cardiac history, and adjuvant chemotherapy administration (AT vs. T) were collected. A logistic regression analysis was performed to estimate independent predictors of AT vs. T chemotherapy. Overall survival (OS) was estimated at 3 years. Results: We identified 3348 patients, including 1679 (50.2%) who received chemotherapy for T1a/bN0 (32.5%), T1cN0 (55.5%), T2N0 (57.0%) and T3/T4N0 (49.6%) disease. Of those, 984 (58.6%) received T, 420 (25.0%) received AT and 275 (16.4%) received other chemotherapy. AT use was associated with larger tumor size; T1a/bN0 (13.6%), T1cN0 (21.3%), T2N0 (31.6%) and T3/T4N0 (34.9%). In a multivariate analysis, independent predictors of AT vs. T were age, region treated in the USA, tumor size and presence of prior cardiac risk factors or pre-existing cardiac disease. OS at 3 years was 91% for T and 86% for AT (p 0.03). Conclusions: Approximately half of older patients diagnosed with node negative TNBC received adjuvant chemotherapy. T-based regimens were more commonly used than AT regimens. Younger age, higher stage and lack of cardiac comorbidities correlated with use of AT compared to T. Continued investigation of the benefit of adjuvant chemotherapy in older patients may assist in clinical decision making.
卡托普利致双侧颌下腺肿大一例
Authors: 高晓丽, 张辉, 张平
Journal: BMJ (2005)

患者男,53岁,因头晕1 d就诊.既往体健,无过敏史.查体:体温36.2℃,脉搏75次/min,血压168/110 mm Hg(1 mm Hg=0.133 kPa).神志清醒,心肺无异常,双下肢无水肿.临床诊断为高血压病2级.予口服卡托普利25 mg 10 min后,双侧颌下进行性肿胀,均可触及核桃大小肿块,伴头晕加重、眼胀,无胸闷、咳嗽,无皮疹、皮肤瘙痒.查体:体温36.2℃,脉搏80次/min,呼吸16次/min,血压130/90 mm Hg.全身皮肤黏膜无皮疹、出血点,无结膜充血;双侧颌下腺肿大,可触及3 cm×2 cm×3 cm肿块,质软,无触痛;心肺无异常,双下肢无水肿.实验室检查:血、尿常规正常;肝、肾功能正常;心电图正常.初步诊断为卡托普利的不良反应.嘱患者多饮水,观察2 h后颌下腺肿块逐渐缩小,次日晨症状和体征消失。
Turnbull-Cutait Pull-Through—An Old Procedure With a New Indication?
Authors: Jose G. Guillem, Raul Cutait, Fehza Remzi
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Combination of transurethral pneumatic and ultrasonic cystolithotripsy: a clinical analysis of 30 cases
Authors: Sen-xin Wei, Xian-an Cai, Ji-zheng Wang, Yi Cai, Qing-jun Meng
Journal: BMJ (2013)

The clinical data of 30 patients with vesical calculus of 1.5 cm to 4 cm in diameter, who underwent combination of transurethral pneumatic and ultrasonic cystolithotripsy, were retrospectively analyzed. During the procedure the resectoscopic sheath was inserted into bladder through urethra, then the nephroscope was placed through the sheath. When the stone was located, the ultrasonic and pneumatic devices were used for lithotripsy and the fragments were cleared out. The procedures lasted from 10 to 25 min, all operations were successful. Transurethral resection of prostates (TURP) was performed simultaneously in 28 patients. No serious bleeding, bladder injury or transurethral resection syndrome occurred. One patient with simultaneous TURP developed bladder neck contracture one month after surgery and was later cured by endoresection. No residual chip or stone recurrence was detected. This procedure appears to be safe and highly efficient with low rate of urethrostenosis and is suitable for simotaneous prostate surgery.


Key words: 
Bladder calculi; Lithotripsy
Improved prognostication for lung cancer patients from computed tomography imaging using deep learning.
Authors: Felipe Torres, Shazia Akbar, Felix Baldauf-Lenschen, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2020)

2044 Background: Clinical TNM staging derived from computed tomography (CT) imaging is a key prognostic factor for lung cancer patients when making decisions about treatment, monitoring, and clinical trial eligibility. However, heterogeneity among patients, including by molecular subtypes, may result in variability of survival outcomes of patients with the same TNM stage that receive the same treatment. Artificial intelligence may offer additional, individualized prognostic information based on both known and unknown features present in CTs to facilitate more precise clinical decision making. We developed a novel deep learning-based technique to predict 2-year survival from pretreatment CTs of pathologically-confirmed lung cancer patients. Methods: A fully automated, end-to-end model was designed to localize the three-dimensional (3D) space comprising the lungs and heart, and to learn deep prognostic features using a 3D convolutional neural network (3DCNN). The 3DCNN was trained and validated using 1,841 CTs of 1,184 patients from five public datasets made available in The Cancer Imaging Archive. Spearman’s rank correlation (R) and concordance index (C-index) between the model output and survival status of each patient after 2-year follow-up from CT acquisition was assessed, in addition to sensitivity, specificity and accuracy stratified by staging. Results: 3DCNN showed an overall prediction accuracy of 75.0% (R = 0.32, C-index = 0.67, p &lt; 0.0001), with higher performance achieved for stage I patients (Table) . 3DCNN showed better overall correlation with survival for 1,124 patients with available TNM staging, in comparison to TNM staging only (R = 0.19, C-index = 0.63, p &lt; 0.0001); however, a weighted linear combination of both TNM staging and the 3DCNN yielded a superior correlation (R = 0.34, C-index = 0.73, p &lt; 0.0001). Conclusions: Deep learning applied to pretreatment CT images provides personalized prognostic information that complements clinical staging and may help facilitate more precise prognostication of patients diagnosed with lung cancer. [Table: see text]
川芎嗪治疗再生障碍性贫血临床观察
Authors: 谢圣兰
Journal: BMJ (2006)

对22例再生障碍性贫血患者在使用吡唑甲氢龙基础上加用川芎嗪治疗,并同12例对照组比较.结果显示治疗3个月后,川芎嗪组患者血红蛋白、网织红细胞、白细胞的改善均优于对照组(P＜0.05).两组血小板略有升高,但差异无统计学意义.提示川芎嗪可有效地改善骨髓造血功能的恢复,可用于再生障碍性贫血的治疗。
Clinical analysis of 22 cases with gastrointestinal stromal tumors
Authors: Chang-hui Wang, Qing-jiang Zhi
Journal: BMJ (2010)

The clinical data of 22 cases with gastrointestinal stromal tumors were retrospectively analized.The main clinical manifestations were gastrointestinal bleeding (14/22),abdominal discomfort (5/22) and abdominal lump (3/22),stomach was the most common site of the tumor (14/22).All 22 cases underwent surgical treatment and pathological examination confirmed that 12 cases were benign.Immunohistochemical results showed that 68% cases were negative in solubility acid protein-100 (S-100),and the positive rates of tyrosine-protein kinase acceptor 117 (CD117),hemopoietic stem cell antigen 34 (CD34) and negative rate of smooth muscle actin (SMA) were all 73%.Eighteen cases were followed up for 1-5 years after operation,among them 3 died.The survival was closely related to the size,the pathological characteristics and the recurrance of the tumor as demonstrated by multivariate Cox regression analysis.Since gastrointestinal stromal tumor has no specific clinical manifestations,preoperative diagnosis is difficulty,so surgical resection and subsequent pathological examination is used for confirmation of diagnosis,as well as treatment of the disease.

Key words: 
Gastrointestinal stromal tumors; Treatment outcome
DUTRENEO Trial: A randomized phase II trial of DUrvalumab and TREmelimumab versus chemotherapy as a NEOadjuvant approach to muscle-invasive urothelial bladder cancer (MIBC) patients (pts) prospectively selected by an interferon (INF)-gamma immune signature.
Authors: Enrique Grande, Félix Guerrero, Javier Puente, Isabel Galante, Ignacio Duran, Mario Dominguez, Teresa Alonso Gordoa, Javier Burgos, Albert Font, Alvaro Pinto, Mario Alvarez-Maestro, Oscar Reig, José Maroto, Xavier Garcia del Muro, Patricia Galvan, Juan Fernando Garcia, Nuria Malats, Aleix Prat, Francisco X. Real, Daniel Castellano
Journal: Journal of Clinical Oncology (2020)

5012 Background: Cisplatin-based neoadjuvant chemotherapy (CT) followed by radical cystectomy (RC) is a standard treatment for MIBC. PD-1/L1 inhibitors as single agent induce pathological complete responses (pCR) in this setting. Predictors of response are still ill defined. DUTRENEO trial aimed to prospectively explore the activity of anti-PDL1 + anti-CTLA4 vs CT in pts selected according to a tumor pro-inflammatory IFN-gamma signature (tumor immune score, TIS). Methods: Cisplatin-eligible pts with urothelial MIBC (cT2-T4a, N≤1, M0) candidates to RC were classified as “hot” or “cold” according to a tumor TIS determined by Nanostring technology. Patients with "hot" tumors were randomized to DU 1500 mg + TRE 75 mg every 4 weeks x 3 cycles or standard cisplatin-based CT (GEMCIS or MVACdd). Pts in the “cold” arm received standard CT. Primary endpoint was to achieve ≥8 pCR in the DU+TRE arm. PDL1 expression was assessed using immunohistochemistry. Results: 61 pts were recruited in 10 sites between oct-2018 and dec-2019. Pts randomized in the “hot” arms received standard CT (n = 22) or DU+TRE (n = 23) and had a pCR rate of 8/22 pts (36.4%) vs 8/23 pts (34.8%), respectively [OR = 0.923 (0.26 – 3.24)]. In the “cold” arm, 16 pts received CT obtaining a pCR rate of 68.8% (11/16 pts). There were more PDL1 low tumors in the "cold" TIS arm (10/12, 83.3%). pCR rate by PDL1 status is shown in the table. One pt in the DU+TRE arm refused RC. Full treatment was delivered to 81.3% of CT "cold" vs 59.1% of CT "hot" vs 73.9% in the DU+TRE arm pts. Grade 3-4 toxicities were more frequent in the CT arms. Conclusions: The combination of DU+TRE is safe and active in MIBC patients in the neoadjuvant setting. Nevertheless prospective stratification by a pro-inflammatory IFN-gamma signature failed to select patients more likely to benefit from IO vs CT in this context. Further studies are required to guide treatment selection. Clinical trial information: NCT03472274 . [Table: see text]
Partner engagement and patients’ receipt of colorectal cancer surveillance.
Authors: Christine M Veenstra, Paul Abrahamse, Arden M. Morris, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2020)

e19106 Background: Over 50% of survivors of colorectal cancer do not receive guideline-concordant surveillance. In light of growing recognition that members of couples influence each other’s health behaviors, we sought to describe partner engagement in surveillance and evaluate associations between partner engagement and patient receipt of surveillance. Methods: In 2019 we surveyed patients who, in 2014-18, underwent resection of Stage III colorectal cancer and were seen at a community oncology practice, an academic cancer center, or reported to Georgia SEER (current RR 46%). Patients gave a separate survey to their partner. 254 partners (68% RR) completed surveys. Using existing measures, we assessed 3 partner-reported elements of engagement: 1) informed about surveillance; 2) involved (extent of and satisfaction with) in surveillance; 3) aware of patients’ values/preferences. Each measure was scored on a continuous scale with higher scores indicating greater engagement. We assessed patient receipt of surveillance by patient-report of receipt of CEA blood test, imaging, and colonoscopy/sigmoidoscopy (all y/n response). We performed multivariable regression analyses to assess associations between each element of partner engagement and patient receipt of surveillance, controlling for important partner- and patient-level variables. Results: Most partners (85%) were &gt; age 50, female (64%), and white (86%). 27% had &lt;high school education. Most patients (60%) had colon primary (vs rectal), received chemotherapy (95%), and were 3-4 years out from diagnosis (62%). Female partners and those with &lt;high school education were more likely to report a greater extent of involvement; Partners &lt; age 50 were more likely to report greater satisfaction with involvement. Female partners, those with &lt;high school education, and partners of patients who received chemotherapy were more likely to report greater awareness (all p &lt; 0.05). Being informed did not vary by partner or patient factors. Having a more aware partner was associated with greater patient receipt of surveillance colonoscopy/sigmoidoscopy (p = 0.01). Receipt of surveillance CEA or imaging did not vary by partner engagement. Conclusions: Partner engagement in patients’ surveillance varied by partner age, gender and education. Partner awareness of patient preferences was associated with patient receipt of surveillance colonoscopy/sigmoidoscopy. Our findings suggest that interventions to engage partners in patients’ surveillance may improve receipt of guideline-concordant care for survivors of colorectal cancer.
Comprehensive analysis of Excision repair complementation group 1, Glutathione S-transferase, Thymidylate synthase, and Uridine diphosphate glucuronosyltransferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI
Authors: H. Kim, B. Seo, J. Kim, S. Oh, S. Lee, S. Kim, H. Kwon
Journal: Journal of Clinical Oncology (2009)

e15580 Background: Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens. Oxaliplatin and irinotecan have shown to be effective in the treatment of gastric cancer. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, GST, TS, and UGT1A1predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Methods: Total genomic DNA was extracted from whole blood of patient. The PCR- restriction fragment length polymorphism (RFLP) method was applied to detect the known variant sites of ERCC1, GST, TS, and UGT1A1. Results: Response rate of FOLFOX (N=75) was 24%. Grade 3–4 neutropenia and neurotoxicity were observed 34.7% and 16%, respectively. TTP and OS of 1 st line administration of FOLFOX (N=35) was 3.1 months (95% CI, 0.1–6.1 months) and 13.9 months (95% CI, 12.2–15.6 months). Only the GSTM1 positive genotype showed a significantly better time to progression (P=0.023). But significant genotype variation of TS, GST and ERCC1,which assumed to affect to activity of oxaliplatin was not observed to RR, toxicity, and overall survival. Response rate of FOLFIRI (N=74) was 23%. Grade 3–4 neutropenia and diarrhea were observed 55.4% and 9.5%, respectively. TTP and OS of 1 st line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5–6.4 months) and 19.0 months (95% CI, 8.5–29.5months). Low expression type (2R/2R, 2R/3C, and 3C/3C) of TS was associated with high incidence of grade ≥3 neutropenia. But significant genotype variation of UGT1A1,which assumed to affect to toxicity of irinotecan was not observed to RR, toxicity, and survival. Conclusions: In this study, GSTM1 positive genotype showed a significantly better time to progression in the advanced gastric cancer treated with FOLFOX. Low expression type (2R/2R, 2R/3C, and 3C/3C) of TS was associated with high incidence of grade ≥3 neutropenia in the advanced gastric cancer treated with FOLFIRI. Well designed prospective trial will be clearly identifying relations between chemotherapy and genetic variations. No significant financial relationships to disclose.
The potential roles of deubiquitinating enzymes in brain diseases
Authors: Key-Hwan Lim, Jae-Yeol Joo, Kwang-Hyun Baek
Journal: Ageing Research Reviews (2020)

Most proteins undergo posttranslational modification such as acetylation, methylation, phosphorylation, biotinylation, and ubiquitination to regulate various cellular processes. Ubiquitin-targeted proteins from the ubiquitin-proteasome system (UPS) are degraded by 26S proteasome, along with this, deubiquitinating enzymes (DUBs) have specific activity against the UPS through detaching of ubiquitin on ubiquitin-targeted proteins. Balancing between protein expression and degradation through interplay between the UPS and DUBs is important to maintain cell homeostasis, and abnormal expression and elongation of proteins lead to diverse diseases such as cancer, diabetes, and autoimmune response. Therefore, development of DUB inhibitors as therapeutic targets has been challenging. In addition, understanding of the roles of DUBs in neurodegeneration, specifically brain diseases, has emerged gradually. This review highlights recent studies on the molecular mechanisms for DUBs, and discusses potential therapeutic targets for DUBs in cases of brain diseases.