tbuckley/cabot-search huggingface dataset:
Non-small cell lung cancer: Analysis using mass cytometry and next generation sequencing reveals new opportunities for the development of personalized therapies.
Authors: Susan Raju Paul, Alexander Bagaev, Ivan Valiev, Vladimir Zyrin, Aleksandr Zaitsev, Daniyar Dyykanov, Katerina Nuzhdina, Nikita Kotlov, Felix Frenkel, Skylar Korek, Patrick Reeves, Diane L. Davies, Cameron D Wright, Harald Ott, Ashok Muniappan, Maria Tsiper, Nathan Fowler, Michael Lanuti, Ravshan Ataullakhanov, Mark C Poznansky
Journal: Journal of Clinical Oncology (2020)

e21026 Background: Comprehensive molecular profiling and the use of biomarkers as companion diagnostics have transformed precision medicine for cancer patients. To identify patient-specific tumor microenvironment and biomarker profiles, we assessed the accuracy of our deconvolution algorithm in identifying cellular compositions from whole exome (WES) and whole transcriptome (RNA-seq) sequencing of solid tumors compared with cell populations identified by Mass Cytometry by Time of Flight (CyTOF) in surgically resected tissue from non-small cell lung cancer (NSCLC) patients. Methods: Resected NSCLC tissue was divided for RNA-seq and WES of whole tissue (n = 9) and for generating tissue single cell suspensions through mechanical dissociation and enzymatic digestion (n = 11). Bulk RNA-seq and CyTOF were performed on all cell suspensions. Cellular phenotypes were identified using clustering algorithms in CyTOF and predicted from bulk RNA-seq using our proprietary computational method. Results: Cellular composition reconstructed from RNA-seq correlated with the composition detected by CyTOF (R 2 = 0.922, n = 7) from cell suspensions. To recover the cell percentage from bulk RNA-seq, a machine learning framework was trained on the cell compendia comprising 7,117 unique cell type RNA-seq profiles. A two-stage hierarchical learning procedure generated a gradient boosting Light GBM model that included training on artificial RNA-seq mixtures of different cell types. With this method, we found that stromal and malignant cells were depleted during single cell suspension preparation, resulting in statistically significant differences in the tumor cell composition reconstructed from solid tissue and single cell suspensions. Immune cell types namely T cells and macrophages were similarly represented in both the bulk tumor tissue and matched single cell suspensions. Transcriptomics revealed a subgroup of patients whose tumors were B-cell-enriched, which was validated in other NSCLC cohorts and was associated with greater CD4+ and CD8+ T cell infiltration and improved clinical outcomes. Conclusions: Since preparation of single cell suspensions leads to the loss of several cellular components, RNA-seq of tumor bulk tissue better describes the molecular and cellular properties of the tumor microenvironment. The combination of RNA-seq and WES of tumor tissue provides a comprehensive profile of cellular composition, suggesting that this combination is ideal for precision medicine applications.
原发性失眠的针灸治疗
Authors: 郭静
Journal: BMJ (2008)

失眠属于中医学所指的目不瞑、卧不安、不寐等.中医认为睡眠由心神所主,神不安则睡眠不佳,脏腑功能失调,阴阳失衡,则难以保持良好的睡眠.中医药在调整睡眠、治疗不寐方面积累了丰富的临床经验,而针灸作为中医学的重要组成部分,在治疗失眠方面显示出一定的优势,对于入睡困难、中间易醒及早醒型的失眠均可应用.
芪莪散治疗肠易激综合征25例临床观察
Authors: 余国兵
Journal: BMJ (2007)

肠易激综合征(IBS)指的是一种以腹痛和腹部不适伴排便习惯改变为主的功能性肠病,是最常见的一种功能性肠道疾病.近几年来,患病率处于上升趋势,综合治疗,采取解痉、止泻、通便和助消化、抗抑郁治疗等措施,虽然缓解症状快,但易反复发作,不良反应大.本研究采用芪莪散加减方剂治疗,取得了较好的疗效。
原发肾病综合征合并隐球菌脑膜炎三例
Authors: 张晓东, 宋保利
Journal: BMJ (2005)

新型隐球菌脑膜炎是最常见的中枢神经系统真菌病.肾病综合征患者由于长期应用抗生素、激素及免疫抑制剂,影响了机体的免疫能力,可并发新型隐球菌脑膜炎.但肾病综合征并发此症发病率较低,其临床表现复杂多样,易误诊为其他脑膜炎疾病。
Personalized treatment of a maintenance hemodialysis patient complicated with hypertension and tuberculosis
Authors: Yinan Li, Jun Zhang
Journal: BMJ (2017)

男性67岁、糖尿病肾病慢性肾脏病5期患者，因肺结核活动期行抗结核药物，后出现反复血压异常升高，常规降压及改变透析模式均无明显好转，从药代动力学途径和抗结核药物代谢途径两方面调整降压及抗结核药物，血压得到控制。提示，血透患者病情的不同阶段高血压的原因不尽相同，治疗高血压观察个体的特殊性，个体化治疗。
Evaluation of Genexus system that automates specimen-to-report for cancer genomic profiling within a day using liquid biopsy.
Authors: Siew-Kee Kee Low, Ken Uchibori, Rie Hayashi, Hiu Ting Chan, Ryo Ariyasu, Satoru Kitazono, Noriko Yanagitani, Makoto Nishio, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2020)

3538 Background: Genomic profiling of patients’ tumors using NGS system help in facilitating molecular-guided therapy. The turnaround time from specimen to report by the NGS system is important to deliver result timely for clinical decisions. The Genexus Integrated Sequencer automates all steps of the targeted NGS workflow starting from nucleic acid of formalin-fixed paraffin-embedded tissues or plasma that significantly reduce laborious procedures. Importantly, the whole specimen-to-report workflow delivers results in a single day. In this study, we evaluated detection rate of alteration using Oncomine Precision Assay (OPA) on Genexus system with cell-free DNA (cfDNA) from non-small cell lung cancer (NSCLC). Methods: Among the cfDNA from 48 plasma samples of NSCLC were evaluated, 19 were newly-diagnosed cases with EGFR mutations in cancer tissues and 29 cases were patients who experienced progression of disease after first line of EGFR, ALK or ROS1-targeted therapy. 13-20ng of input cfDNA were subjected to automated Genexus Integrated Sequencer for library construction using OPA panel, templating and sequencing. OPA panel covers actionable hotspot mutations, copy number gains or loss, fusion drivers. The concordance of mutation profiles between the tumor tissue and cfDNA and detection of a resistance mutation(s) during molecular-targeted therapy were evaluated. Results: The sequencing resulted in median overall reads of 8,698,358, median overall depth of 30,648 (range 15,069-48,707) and median molecular coverage of 1,595 (range 859-2,550). Among 48 samples examined, 44 were detected to carry at least one somatic mutation, giving the detection rate of 92%. A total of 17 of 19 newly diagnosed EGFR-positive patients were also detected to carry EGFR mutations. Importantly, these 17 patients carry the same mutation that was found in tissue samples implying complete concordance. In addition, we found novel resistance mutations in plasma of the patients who were under EGFR, ALK or ROS1 targeted therapies. Conclusions: Genexus Integrated Sequencer is a fully automated and highly accurate NGS system with a 1-day turnaround time that could assist clinicians to make more timely decision. Novel actionable, resistance mutations were detected using OPA panel that provide potential options for molecular-guided therapy and may help the better understanding of resistance mechanism of targeted therapy.
Patho-genomic feature of PI3K / AKT / mTOR pathway mutations in Chinese patients with non-small cell lung cancer.
Authors: Weiwei Li, Yuan Qiu, Hanzhang Chen, Haihong Yang, Qiuhua Deng, Liping Liu, Dakai Xiao, Changbin Zhu, Wenxi Jiang, Di Shao, Yongping Lin, Jianxing He
Journal: Journal of Clinical Oncology (2020)

e21049 Background: Inhibition of PI3K/AKT/mTOR pathway has emerged as a promising anticancer strategy. Measuring genetic alterations in PI3K/AKT/mTOR pathway are critical for clinical decision making for patients with lung cancer. This study aims to analyze PI3K/AKT/mTOR pathway-related gene mutations in non-small cell lung cancer (NSCLC) in a consecutive cohort. Methods: 536 surgically resected tumor tissues were collected. Target region capture sequencing for 508 cancer-related genes was conducted on MGI-seq 2000 platform. Results: PI3K/AKT/mTOR pathway genes were mutated in 120 samples (22.4%). Female or older patients displayed higher mutation incidence of PI3K/AKT/mTOR pathway (P = 0.06 for female, P = 0.05 for patients ≥60 y). In NSCLC samples, mutations mainly occurred in NF1/2(18/499), PTEN (7/499), MTOR (4/499), TSC1/2(18/499), PIK3CA (26/499), PDK1 (2/499), AKT1/2/3 (5/499) and KRAS (49/499) genes. Genetic alterations of AKT2 (p = 0.003), mTOR (P = 0.03), PTEN (P = 0.005) and PIK3CA (P &lt; 0.001) are preferred to occur in squamous NSCLC. PIK3CA variants (p.E542K, p.E545K, p.Q546K) were more enriched in non-squamous NSCLC, while amplification of PIK3CA was more prevalent in squamous NSCLC (P = 0.038). Histologically, TSC1/2 mutations were more correlate with micro-invasion subtype in non-squamous NSCLC (P = 0.002). Meanwhile, PIK3CA alterations, especially, amplification occurred more often in keratinizing squamous NSCLC (P &lt; 0.001). In addition, four patients with biallelic NF1 loss of function mutations were exclusively found in non-squamous NSCLC without co-occurrence of mutation in known driver genes like EGFR or TP53, which indicated biallelic loss of function of NF1 might be sufficient to drive oncogenesis of non-squamous NSCLC. Conclusions: PI3K/AKT/mTOR pathway alterations present a heterogenous distribution across various types of lung malignancies especially in NSCLC. As more small molecule inhibitors developed to target PI3K/AKT/mTOR pathway, this study might shed light on further clinical investigation of these lately developed therapeutic approaches. [Table: see text]
A Frame of Reference for Assessing the Intensity of Exertional Dyspnoea During Incremental Cycle Ergometry
Authors: J. Alberto Neder, Danilo C. Berton, Luiz E. Nery, Wan C. Tan, Jean Bourbeau, Denis E. O'Donnell
Journal: European Respiratory Journal (2020)

Assessment of dyspnoea severity during incremental cardiopulmonary exercise testing (CPET) has long been hampered by the lack of reference ranges as a function of work rate (WR) and ventilation (V̇E). This is particularly relevant to cycling, a testing modality which overtaxes the leg muscles leading to a heightened sensation of leg discomfort. Reference ranges based on dyspnoea percentiles (0–10 Borg scale) at standardised WRs and V̇E were established in 275 apparently healthy subjects aged 20–85 (131 men). They were compared with values recorded in a randomly selected “validation” sample (N=451, 224 men). Their usefulness in properly uncovering the severity of exertional dyspnoea were tested in 167 subjects under investigation for chronic dyspnoea (“testing sample”) who terminated CPET due to leg discomfort (86 men). Iso-WR and, to a lesser extent, iso-V̇E reference ranges (5th–25th, 25th–50th, 50–75th and 75th–95th percentiles) increased as a function of age, being systematically higher in women (p&lt;0.01). There was no significant differences in percentiles distribution between “reference” and “validation” samples (p&gt;0.05). Submaximal dyspnoea-WR scores lied within the 75th–95th or &gt;95th percentiles in 108/118 (91.5%) subjects of the “testing” sample who showed physiological abnormalities known to elicit exertional dyspnoea i.e. , ventilatory inefficiency and/or critical inspiratory constraints. In contrast, dyspnoea scores typically lied in the 5th–50th range in subjects without those abnormalities (p&lt;0.001). This frame of reference might prove useful to uncover the severity of exertional dyspnoea in subjects who otherwise would be labeled as “non-dyspneic” while providing mechanistic insights into the genesis of this distressing symptom.
High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer—Reply
Authors: Tessa G. Steenbruggen, Lars C. Steggink, Gabe S. Sonke
Journal: JAMA Oncology (2020)

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Eosinophilic colitis in cancer patients.
Authors: Shruti Khurana, Hamzah Abu-Sbeih, Weijie Ma, Wai Chin Foo, Hao Chi Chi Zhang, Yinghong Wang
Journal: Journal of Clinical Oncology (2020)

e16500 Background: Eosinophilic colitis (EoC) is a rare form of eosinophilic gastrointestinal disease characterized by diffuse eosinophilic infiltration in the deep lamina propria and extensive crypt epithelial injury with apoptosis and crypt abscesses. The pathophysiology is still unclear and associated with many etiologies. We described the clinical characteristics of EoC in cancer patients. Methods: We retrospectively reviewed the pathology report of the colonic samples from endoscopy or surgical resection obtained between 01/2000 and 12/2018 at MD Anderson Cancer Center. The included cases had significant eosinophilia with key word description of “numerous”, “many” or “dominant” on the pathology. Clinical data were collected and analyzed. Results: A total of 41 cases were included based on the inclusion criteria with 34% men, with a median age of 60. 27% had NSAID use and 40% were smokers. One-fourth had co-existing autoimmune conditions. 78% had cancer diagnosis (hematologic at 41%, followed by genitourinary and gastrointestinal origin) with the rest carrying no cancer diagnosis. Half of the cases received chemotherapy with median duration of 180 days between chemotherapy to EoC onset. Common EoC symptoms included diarrhea, and abdominal pain which were present in 76% patients. Diarrhea was more prevalent in patients who received chemotherapy (85% vs 42%). Median duration of EoC symptoms was shorter in cancer patients (240 vs 30 days) and chemotherapy exposure (120 vs 30 days). Hospitalization for EoC was required in 15% cases. Most commonly administered treatment for EoC was immunosuppressants (22%). Normal colonoscopy was reported in 88% patients at the time of EoC diagnosis. All-cause mortality was 37% and was mostly related to underlying malignancy. Conclusions: The disease course of EoC in cancer patients on chemotherapy is not well defined. It appeared to be less severe than non-cancer patients, which raised the possibility of two separate subclasses of this disease entity. Cancer/chemotherapy related EoC could be a GI specific paraneoplastic manifestation, and behave differently from other etiology. [Table: see text]
美国高血压管理新模式简介及启示
Authors: 姚崇华
Journal: BMJ (2011)

美国从1988年至2000年间3次全国性的调查结果显示,其高血压的知晓率、治疗率和控制率分别在70%、50%～60%和30%左右[1],十几年问高血压的控制率没有很大变化.为了进一步提高高血压管理的控制率,美国慢性病保健的新模式不断发展和完善,目前美国高血压控制率已达到50%。
人乳头状瘤病毒感染与子宫颈癌
Authors: 卞美璐, 陈庆云
Journal: BMJ (2009)

子宫颈癌是一种感染性疾病,主要由高危型人乳头状瘤病毒(human papillomavirus,HPV)感染所致.近年来,临床医生在宫颈癌和癌前病变的诊治与预防实践中对有关HPV的研究予以了关注,本文就一些热点问题予以简述。
Clinicopathological demographics of malignant melanoma of the vulva and vagina in Japan: Japanese Gynecologic Oncology Group (JGOG)/Japanese Skin Cancer Society (JSCS)—Intergroup Study.
Authors: Shin Nishio, Dai Ogata, Yoshio Kiyohara, Munetaka Takekuma, Mikio Mikami, Tomoka Usami, Hiroyuki Kanao, Eiji Kobayashi, Eiji Kondo, Koji Nishino, Yuichiro Miyamoto, Akiko Furusawa, Yasuhiro Fujisawa, Yuki Yamamoto, Tatsuya Kaji, Hironobu Ihn, Takayuki Enomoto
Journal: Journal of Clinical Oncology (2020)

e22106 Background: Malignant melanomas of the vulva (VuM) and vagina (VaM) represent a unique subgroup of malignant melanomas with important differences in biological properties and treatment. In Japan adequate surveys have not been performed.The objective of this study was to elucidate the clinicopathological demographics and outcomes of VuM and VaM in Japan. Methods: Women with invasive VuM or VaM were identified from a medical records. Data on clinician (Gynecologist or Dermatologist), age, location, node status, ulceration, mitotic count, histologic subtype, American Joint Committee on Cancer (AJCC) stage, primary surgery, and surgical margin were collected. The Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS). Univariate and multivariate regression models were used to identify factors significantly related to survival. Results: A total of 217 patients (pts) were identified; 109 (50.2%) had VuM and 108 (49.8%) had VaM. The median age of the subjects was 67 years (range [R], 29-96 years). Surgery was performed in 84.3% of the women with VuM and 83.3% of those with VaM. The median depth of invasion was 4.5 mm (R, 0.1-12 mm). Ulceration was documented in 47.9% (104/217) of the lesions. Nodal status was positive in 60 pts (27.6%), negative in 149 pts (68.7%), and unknown in 8 (3.7%) pts. The AJCC stage was stage I in 37 pts (17.1%), II in 106 pts (48.8%), III in 46 pts (21.2%), and IV in 28 pts (12.9%). Nodular melanoma was the most common subtype (48.8%). The median PFS was 16.8 months in pts with VuM (95% confidence interval [CI] 23.1-87.7) and 15.6 months in pts with VaM (95% CI 8.4-12.6). The median OS was 43.9 months (95% CI 60-138) in pts with VuM and 31.1 months (95% CI 24.8-45.3) in pts with VaM. Univariate analysis showed that vaginal location, nodal metastases, stage, surgery, and surgical margin were associated with poorer PFS, whereas nodal status, histologic subtype, stage, surgery, and surgical margin were associated with poorer OS. Multivariate analysis showed that only disease stage (hazard ratio [HR] = 3.09; 95% CI = 1.73-5.49) was associated with poorer PFS. Surgical margin was the only independent factor influencing OS (HR = 2.39; 95% CI = 1.48-3.80). Conclusions: The overall outcomes of VuM and VaM remain poor in Japan. In particular, the outcomes of VaM are worse than those reported previously. AJCC stage and surgical margin are important predictors of survival. Regardless of disease stage, suitable surgical resection is required. Clinical trial information: UMIN000025968.
Preliminary efficacy data of platinum-pretreated small cell lung cancer (SCLC) cohort of NCI 9881 study: A phase II study of cediranib in combination with olaparib in advanced solid tumors.
Authors: Joseph W. Kim, Navid Hafez, Hatem Hussein Soliman, Siqing Fu, Shumei Kato, Primo Lara, Ulka N. Vaishampayan, Albiruni Ryan Abdul Razak, Dana Backlund Cardin, Pamela N. Munster, Joseph Paul Eder, Elizabeth M. Swisher, Andrew B. Nixon, Abhijit Patel, Yu Shyr, S. Percy Ivy, Patricia LoRusso
Journal: Journal of Clinical Oncology (2020)

9065 Background: Cediranib, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrated clinical efficacy in patients with advanced solid tumors carrying a germline BRCA mutation. We therefore tested the anti-tumor activity of cediranib and olaparib combination in patients (pts) with advanced solid tumors. Here, we report the data from the SCLC cohort. Methods: This multi-institutional, two-stage, phase 2 study enrolled pts with metastatic SCLC previously treated with a minimum of one prior line of platinum-based chemotherapy in advanced setting. Patients were treated with cediranib 30mg po daily plus olaparib 200mg po BID until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by RECIST v1.1. Baseline tumor biopsies were obtained for biomarker analyses. Results: Baseline characteristics of the 25 pts enrolled are summarized below. The overall ORR rate was 28% (95% CI: 0.104,0.456). Median duration of response was 3.8 months (mos). Six of 8 pts had an objective response lasting longer than 3 mos up to 10.3 months. Disease control rate (# of pts with CR, PR or SD / # evaluable pts) was 88% (95% CI: 0.75,1.01). Median progression free survival was 4.1 mos (95% CI: 2.3, 6.2). Median OS was 5.5 mos (95% CI: 3.4, NA). Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 14 of 25 (56%). G3/4 AEs occurring in &gt; 10% of pts were hypertension (21%), fatigue (17%) and weight loss (13%). Conclusions: The cediranib/olaparib combination resulted in promising clinical activity with ORR of 28% in biomarker-unselected pts with platinum-pretreated SCLC. The regimen required prompt initiation of antihypertensives, but AEs were overall manageable. Analyses of mutation status in homologous recombination DNA repair genes are going and will be correlated with clinical activity. Clinical trial information: NCT02498613. [Table: see text]
Survey on the prevalence rate of cardiovascular disease in residents over age of 15 years old in Hubei Province
Authors: Qi Pan, Lixin Guo, Yinmei Yang, Chenchang Xiao, Gong Chen, Shiyue Li, Hong Yan
Journal: BMJ (2016)

分析2013年第五次全国卫生服务调查中湖北省部分资料，了解湖北省15岁及以上居民心脑血管疾病患病状况及影响因素。结果显示28 563人中自我报告患有心脑血管疾病683人，患病率2.39%。logistic回归分析显示，年龄大、离退休或失业/无业人员、过去每天吸烟、患有高血压或糖尿病者心脑血管疾病患病率较高。
复方角菜酸酯栓治疗痔的临床和基础研究
Authors: 王振军
Journal: BMJ (2005)

自2000年开始,痔的研究有很多新进展,中华医学会肛肠外科学组、中医肛肠学会和中西医结合肛肠学会均总结既往诊断和治疗经验,分别制订了针对痔的诊治指南,推动了广大医师对痔的重视及痔的各项研究[1,2],改变了临床对痔注重手术切除的片面观点,使包括药物治疗在内的非手术治疗日益得到重视。
Studying the interrelation between the HPV infection status and the morphological features of bladder cancer.
Authors: Tatiana A. Zykova, Alexey N. Shevchenko, Irina A. Khomutenko, Elena V. Filatova, Elena A. Shevyakova, Lilia A. Velikorodnaya, Sergey N Dimitriadi, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e17003 Background: The etiological role of human papillomavirus (HPV) in the development of squamous cell carcinoma of the cervix and larynx is considered proven. At the same time, there are conflicting data in the literature on the role of HPV in the development of bladder cancer (BC). The aim of the present study was to evaluate the prevalence of HPV infection in patients with BC, identifying the relationship between the status of infection and the morphological characteristics of the tumor. Methods: The study included 46 patients (10 women and 36 men) with morphologically confirmed urothelial cancer. Samples of urine, tumor tissue and a healthy bladder mucosa were examined. HPV DNA was determined by real-time PCR. Results: 28 (60.9%) patients were infected with high-risk HPV, including 6 (60.0%) women and 22 (61.1%) men. In 14 (30.4%) patients, HPV DNA was found in the tissue of the bladder mucosa: in 6 (13.0%) cases it was only in tumor tissue, in 4 (8.7%) only in healthy mucosa, in 4 (8.7%) simultaneously in healthy and tumor tissue. HPV DNA was detected in urine in 22 (47.8%) patients. The simultaneous presence of HPV DNA in the tissue of the bladder mucosa and urine was found in 8 (28.6%) HPV-positive patients. Single HPV infection was found in 20 (71.4%) patients, two types were found in 8 (28.6%). When analyzing type diversity, it was found that HPV16 infected 14 (38.9%) patients; HPV18, 31, 39 and 56 were determined in 4 (11.1%) cases each; 33, 52 and 59 types in 2 (5.6%) cases. Chronic inflammation was noted in 12 (26.1%) patients, 6 (50.0%) of them were HPV-positive. Among HPV-positive patients, invasive cancer was registered in 18 (64.3%), non-invasive cancer in 10 (35.7%) patients. Among HPV-negative patients, these rates were 14 (77.8%) and 4 (22.2%), respectively (p &gt; 0.05). In the group of HPV-positive patients, tumors with a low degree of differentiation were found in 16 (57.1%), moderate in 6 (21.4%), high in 6 (21.4%). Among HPV-negative patients, these indicators were 4 (22.2%), 12 (66.7%) and 2 (11.1%), respectively (p &gt; 0.05). Conclusions: HPV infection was detected in 60.9% of patients, including tumor tissue infection in 21.7% of patients. The most common HPV type was HPV16. There was no statistically significant difference between HPV-positive and negative tumors.