tbuckley/cabot-search huggingface dataset:
Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae
Authors: Chenxi Qiu, Huiyan Jin, Irina Vvedenskaya, Jordi Abante Llenas, Tingting Zhao, Indranil Malik, Alex M. Visbisky, Scott L. Schwartz, Ping Cui, Pavel Čabart, Kang Hoo Han, William K. M. Lai, Richard P. Metz, Charles D. Johnson, Sing-Hoi Sze, B. Franklin Pugh, Bryce E. Nickels, Craig D. Kaplan
Journal: Genome biology (2020)

Abstract Background The majority of eukaryotic promoters utilize multiple transcription start sites (TSSs). How multiple TSSs are specified at individual promoters across eukaryotes is not understood for most species. In Saccharomyces cerevisiae , a pre-initiation complex (PIC) comprised of Pol II and conserved general transcription factors (GTFs) assembles and opens DNA upstream of TSSs. Evidence from model promoters indicates that the PIC scans from upstream to downstream to identify TSSs. Prior results suggest that TSS distributions at promoters where scanning occurs shift in a polar fashion upon alteration in Pol II catalytic activity or GTF function. Results To determine the extent of promoter scanning across promoter classes in S. cerevisiae , we perturb Pol II catalytic activity and GTF function and analyze their effects on TSS usage genome-wide. We find that alterations to Pol II, TFIIB, or TFIIF function widely alter the initiation landscape consistent with promoter scanning operating at all yeast promoters, regardless of promoter class. Promoter architecture, however, can determine the extent of promoter sensitivity to altered Pol II activity in ways that are predicted by a scanning model. Conclusions Our observations coupled with previous data validate key predictions of the scanning model for Pol II initiation in yeast, which we term the shooting gallery. In this model, Pol II catalytic activity and the rate and processivity of Pol II scanning together with promoter sequence determine the distribution of TSSs and their usage.
Impact of race and socioeconomic factors on outcome in hepatocellular carcinoma.
Authors: Mahvish Muzaffar, Abdul Rafeh Naqash
Journal: Journal of Clinical Oncology (2020)

e16657 Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer related deaths and sixth leading cause of cancer globally. In USA the incidence of HCC has gradually increased over years.We sought to investigate impact of race and socioeconomic factors on the outcome of HCC in USA. Methods: The SEER database (version 8.3.6) was reviewed for patients with Hepatocellular carcinoma diagnosed between 1990-2016. Cases identified on autopsy or reported only on a death certificate were excluded. Variables included were, age, race, gender, stage, insurance, Pacific Coast Purchased/Referred Care Delivery Areas (PRCDA). Cox proportional hazard regression model was employed to test the association between survival and variables. Results: We identified a total of 87,047 cases of HCC that met the inclusion criteria from SEER database. Mean age was 63.15 yrs.( 63.22-63.07),67% were white,13% black, and others 20%.The Male: Female ratio was 3:1 and 59% of patients belonged to Pacific Coast PRCDA compared to 29% to East PRCDA.43% had localized stage,25% regional, 14% distant and 18% unknown.58% patient had some insurance and 42% were uninsured or unknown status. Patients diagnosed between 1990-2003 had median survival for white (4mos), blacks(3mos), others (7 mos.) (p &lt; .0001) and for the time period 2004-2016, median survival was better,white(13 mos), blacks(10 mons), others(20mos) (p &lt; .001). Conclusions: Outcome for HCC have improved over last two decades, but race and socioeconomic factors continue to impact outcome. Interventions addressing the racial and socioeconomic disparity can result in meaningful improvement in survival. [Table: see text]
Colon and rectal cancer survival in seven high-income countries 2010–2014: variation by age and stage at diagnosis (the ICBP SURVMARK-2 project)
Authors: Marzieh Araghi, Melina Arnold, Mark J Rutherford, Marianne Grønlie Guren, Citadel J Cabasag, Aude Bardot, Jacques Ferlay, Hanna Tervonen, Lorraine Shack, Ryan R Woods, Nathalie Saint-Jacques, Prithwish De, Carol McClure, Gerda Engholm, Anna T Gavin, Eileen Morgan, Paul M Walsh, Christopher Jackson, Geoff Porter, Bjorn Møller, Oliver Bucher, Michael Eden, Dianne L O’Connell, Freddie Bray, Isabelle Soerjomataram
Journal: Gut (2020)

Objectives As part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age and stage at diagnosis. Methods Data from 386 870 patients diagnosed during 2010–2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country, Results (One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage). Conclusions Survival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.
小议“并发”与“合并”和“并发症”与“合并症”
Authors: 左海萍, 汤建文
Journal: BMJ (2012)

并发与合并、并发症与合并症是医学常用词语,容易错用.《现代汉语词典》中对并发一词的解释是:由正在惠的某种病引起(另一种疾病);对合并一词有两种解释,释②是:指正在患某种病的同时又发生(另一种疾病):麻疹合并肺炎.由此可见,并发前后两种病之间是有因果关系的,合并前后两种痛之间,可以是有因果关系的(如麻疹合并肺炎),也可以是无因果关系,或者是临床上不易查明因果关系的.因此,当两种病之间能够明确有因果关系的宜使用并发一词,无因果关系或不易查明有因果关系的应该使用合并一词.比如:《肋骨骨折合并迟发性血胸31例临床分析》[1]中,肋骨骨折与迟发性血胸具有因果关系,使用并发一词重为贴切同理,《重症小儿手足口病合并中枢性呼吸衰竭四倒》[2]中的合并改用并发更好。
ARC-4 study: Efficacy and safety of AB928 plus carboplatin, pemetrexed and a PD-1 antibody in participants with metastatic non-small cell lung cancer (mNSCLC).
Authors: Alexander I. Spira, Paul R. Conkling, Melissa Lynne Johnson, Olivia Gardner, Houston N. Gilbert, Michael Scharville, Fangfang Yin, Kartik Krishnan, Melissa Constance Paoloni, Arvind Chaudhry
Journal: Journal of Clinical Oncology (2020)

e21659 Background: Adenosine, derived from ATP released by dying cancer cells in response to chemotherapy, binds to and activates the A 2a and A 2b receptors on immune cells, resulting in an ineffective anti-tumor immune response. Adenosine receptor blockade may therefore enhance the efficacy of chemotherapy when co-administered with a checkpoint inhibitor. AB928, the first clinical-stage small molecule dual A 2a R/ A 2b R antagonist, is highly potent and was well tolerated in dose escalation studies as a single agent or in combination with chemo/immunotherapy. Methods: ARC-4 (NCT03846310) is a Phase 1/1b, open-label study in participants (pts) with metastatic, locally advanced, or recurrent non-squamous NSCLC with no alternative or curative therapy option. Pts whose tumor has a genetic alteration for which targeted therapy exists must be chemo/immunotherapy naïve. Pts must have ECOG PS 0-1 and at least one measurable lesion. Two escalating doses of AB928 (75 or 150 mg) administered orally daily were given with standard doses of carboplatin, pemetrexed and pembrolizumab. Results: As of 27Dec19, 7 pts have received AB928 in Ph 1: 75 mg (n = 3), 150 mg (n = 4). Number of prior therapies range from 0 to 6 (median = 3). Most treatment emergent AEs (TEAEs) were Grade 1 or 2, with no Grade 5 events. The most common AEs were anemia, nausea and AST elevation. One pt experienced an SAE (Gr4 thrombocytopenia) that was at least possibly related to AB928. One pt discontinued before assessment due to adverse event (muscle weakness). Of the 6 patients with post-baseline disease assessments, all demonstrated decrease size of target lesion. Three patients (43%) achieved a confirmed partial response: one treatment naïve patient, one patient with EGFRmut disease that had previously progressed on treatment with erlotinib and osimertinib, and one patient who had progressed on therapy with ipilimumab and nivolumab. One additional pt had a &gt; 30% decrease in target lesions and findings consistent with new lesions but opted to continue study treatment. Conclusions: Addition of AB928 to carboplatin, pemetrexed and pembrolizumab did not significantly add to the established safety profile of the standard agents. Combination treatment was associated with disease control in all evaluable pts, including responses in those with PD after TKI and immunotherapy. Expansion is on-going in pts with EGFRmut NSCLC that has failed treatment with TKI. Additional updates on the safety, clinical activity, and correlative biomarker results will be presented. Clinical trial information: 03846310.
Analysis on compliance with antihypertensive therapy in patients with cerebral lacuna infarct and hypertension
Authors: Xin Xu, Xiao-lei Hu
Journal: BMJ (2010)

This retrospective case control study compared patient compliance and blood pressurecontrol in hypertensive patients with and without cerebral lacuna infarction on CT in the first affiliated hospital of Harbin Medical University during 2007-01-01 to 2008-01-01. Chi-square test, t test and conditional logistic regression were applied for statistic analysis. We found that,in contrast with the lacuna infarction group, the control group had better compliance with antihypertensive therapy ( χ~2= 16. 661 ,P =0. 000) and more use of long acting medications(χ~2 =10. 736,P =0. 001 ). In both groups, blood pressure was lower in those patients with better compliance. Good compliance and adequate control of blood pressure were statistically associated with lower incidence of cerebral lacuna infarction. We conclude that good control of blood pressure, improved compliance with antihypertensive therapy and use of long acting medications may help to reduce the incidence of cerebral lacuna infarction in hypertensive patients.

Key words: 
Brain infarction;  Hypertension;  Patient compliance
辨证施治对证选用感冒中成药
Authors: 张朔生
Journal: BMJ (2011)

对于感冒这种临床常见病,采用中成药治疗的方法具有标本兼治、副作用小等优点,因而备受广大医务工作者和患者的青睐.然而,治疗感冒的中成药品种繁多,在现实生活中,由于患者或医生盲目、滥用中成药,延误治疗,造成病情迁延日久或加重的现象比比皆是.有的由于误治,造成病情恶化,甚至被夺去生命.作为医务工作者,在临床实践中若能遵循以下原则,对合理使用感冒中成药会大有裨益。
Total laparoscopic distal gastrectomy for gastric cancer: uncut Roux-en-Y anastomosis versus Billroth II anastomosis
Authors: Ting Fei
Journal: BMJ (2019)

Objective
To compare the advantages and disadvantages between Uncut Roux-en-Y anastomosis and Billroth Ⅱ anastomosis in total laparoscopic distal gastrectomy (TLDG) for gastric cancer.


Methods
The clinical data of 132 patients with distal gastric cancer, who underwent TLDG with Uncut Roux-en-Y anastomosis or Billroth Ⅱ anastomosis in the Affiliated Hospital, Medical School of Ningbo University from February 2015 to December 2017, were retrospectively analyzed. There were 52 patients receiving TLDG with uncut Roux-en-Y anastomosis (RA group) and 80 patients receiving TLDG with Billroth Ⅱ anastomosis (BA group).


Results
Compared with BA group,the RA group had a longer operation time [(240.6±49.6) min vs. (202.2±36.4) min, F=2.356, P=0.000]and anastomosis time[(49.1±5.9) min vs. (47.3±4.2) min, F=4.45, P=0.043], more intraoperative blood loss[(128.9±130.0)ml vs. (79.2±62.5) ml, F=5.66, P=0.004]; and short times to first flatus[(2.7±0.8)d vs.(3.0±0.6) d, F=6.61,P=0.031],for liquid diet[(3.7±0.8) d vs.(4.0±0.6) d, F=7.35, P=0.022] and semifluid diet[(4.7±0.8)d vs. (5.0±0.6) d, F=6.43, P=0.013]. No perioperative death occurred in two groups; there were no significant differences in length of postoperative hospital stay [(9.4±4.2)d vs. (10.9±6.4) d, F=0.83, P=0.117]and the incidence of postoperative complication[5.8%(3/52) vs. 8.8%(7/80), χ2=0.40, P=0.527)]. Compared to BA group,alkaline reflex gastritis rate [3.8%(2/52) vs. 52.5%(42/80), χ2=40.04, P=0.000]and marginal ulcer rate were lower[0(0/52) vs. 11.3%(9/80), χ2=6.28,P=0.012]. There was no significant difference in dumping syndrome rate[0(0/52) vs. 3.8%(3/80), χ2=0.20, P=0.158] between two groups.


Conclusion
Uncut Roux-en-Y anastomosis can prevent alkaline reflex gastritis, marginal ulcer and Roux-en-Y stasis syndrome, it may be the preferable technique for reconstruction after total laparoscopic distal gastrectomy.


Key words: 
Stomach neoplasms; Carcinoma; Laparoscopy; Gastrectomy; Anastomosis, Roux-en-Y
Intrathoracic administration of Kushenhuangqi Injection combined with cisplatin in treatment of malignant pleural effusion
Authors: Jia-cai Hu
Journal: BMJ (2008)

Kushenhuangqi Injection is made from Chinese herb medicine flavescent sophora and astragalns roots.Seventy-one patients with malignant pleural effusion were randomly divided into two groups: 36 patients were treated with both intrathoracic Kushenhuangqi Injection and chemotherapeutic agent cisplatin (treatment group) and 35 patients were treated with cisplatin alone.The response rate of treatment group was significantly higher than that of control group (31/36 vs 20/35,u=3.020,P<0.01).The rate of adverse reaction (leucopenia,nausea,vomiting etc.) in treatment group was significantly lower that that of control group.The results indicate that Kushenhuangqi Injection can enhance the therapeutic effect of chemotherapeutic agent and reduce its adverse reaction in treatment 0f malignant pleural effusion caused by carcinoma of the lungs.

Key words: 
Lung neoplasms; Phural effusion,malignant
Collection, storage and results interpretation of sputum specimen
Authors: Qian Liu
Journal: BMJ (2016)

冬春季是呼吸道疾病的高发季节，痰标本的检测需求大大增加。能够正确地采集运送痰标本是获得正确检验结果的重要步骤；痰标本检验结果的正确运用对于疾病诊断和合理用药有很大的指导作用。本文就痰标本检验中与全科医师临床相关的内容做简要介绍。
Application of BODE grading system in evaluating clinical prognosis of chronic obstructive pulmonary disease
Authors: Bing WEi, Xiu-hong Nie, Kui Ren, Yan-ru Han, Yu-lian Zhou
Journal: BMJ (2009)

Objective The aim of this study is to evaluate clinical application of BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index in patients with chronic obstructive pulmonary disease (COPD). Methods Forty patients with stable COPD in Xuanwu Hospital of Beijing during September 2003 to December 2007, were recruited in the study, including 25 men and 15 women, aged 38 to 85 years (with a mean of 62 ± 13 years). BODE index was measured for each patient, one year and three years after recruitment, respectively. Severity of COPD, including number and duration of episodes, length of each hospital stay and times of hospitalization due to acute exacerbation of COPD (AECOPD), were recorded. All data were statistically analyzed with SPSS 13.0 software for windows. Results ①There was a remarkable difference in COPD severity between patients with BODE score equal to or greater than five and these with less than five (P <0.01 ). ①BODE score inversely correlated with forced expired volume at the first second ( FEV1 ) in COPD patients (P < 0.01 for those with BODE score equal to or greater than five and P <0.05 for these with BODE score less than five, respectively). ③BODE score positively correlated with number and duration of acute exacerbation, length of hospital stay and times of hospitalization due to AECOPD (P <0. 01 for those with BODE score equal to or greater than five and P < 0. 05 for those with BODE score less than five, respectively). For patients with COPD, their BODE score in the first year positively correlated with that in the third year ( r = 0.834, P < 0.01 ). Conclusions BODE index is a better indicator to evaluate their condition severity in patients with COPD.

Key words: 
Pulmonary diseases, chronic obstructive;  BODE score;  Prognesis
Prophylactic dihydropyrimidine dehydrogenase (DPYD), and reactive cytidine deaminase (CDA) testing is feasible and reduces severe toxicity in Irish patients receiving 5-fluorouracil (5-FU) based chemotherapy.
Authors: Jake Murphy
Journal: Journal of Clinical Oncology (2020)

3600 Background: 5-Fluorouracil (5-FU) steady state concentrations can vary up to fourfold among cancer patients. 5-FU intolerance and toxicity is associated with reduced activity of the key metabolic enzyme dihydropyrimidine dehydrogenase (DPD) due to polymorphisms of the DPYD gene, as well as mutations in cytidine deaminase (CDA). Since 2012, Bon Secours Hospital, Cork has implemented prophylactic DPYD screening to reduce toxicity. Methods: In this retrospective cohort study, 742 adult cancer patients who underwent reactive or prophylactic DPYD testing in our center between 2012 and 2019 were included. Reactively tested patients were screened prior to 2012. 5-FU related toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and analysed. Frequencies of polymorphisms in DPYD, affecting 5-FU metabolism in patients who experienced severe toxicity are described, in both patients who were retrospectively tested, and in our larger prophylactic patient cohort. Mutations of genes encoding CDA were also analysed. Analysis of type and severity of toxicity, and survival analysis will be presented at the Annual Meeting. Results: 742 patients were tested for DYPD in our centre, of which 704 were prophylactic tests. 11.4% of the patients tested prophylactically were found to have polymorphisms in the DYPD gene. Expectedly, a higher proportion of patients tested reactively were found to have polymorphisms in DYPD (21.9%). 21 out of 34 patients who had severe toxicity had CDA mutations present on testing. Further data involving classification and severity of toxicities, along with survival analysis will be presented at the Annual Meeting. Conclusions: The prevalence of DPYD mutations in Ireland is estimated to be 7-10%, and is putatively responsible for approximately 20% of all severe 5-FU toxicities suffered by cancer patients. Implementing prophylactic DPYD screening is beneficial in reducing toxicities in this setting. Future work will focus on phenotypic measurements of uracil metabolism and pharmacokinetic 5-FU monitoring to further reduce toxicity in patients who do not have DPYD mutations.
Non-invasive detection of urothelial carcinoma (UC) by cost-effective low-coverage whole genome sequencing from urine exfoliated cells DNA.
Authors: Shuxiong Zeng, Dongxing Nai, Yingdie Ye, Jiatao Ji, Zunlin Zhou, Baiyun Wang, Qian Ziliang, Changliang Xu
Journal: Journal of Clinical Oncology (2020)

1552 Background: Urothelial carcinoma (UC) is a malignancy with frequent chromosomal aberrations. The FISH assays were more sensitive as compared to cytology tests. Here we investigated cost-effective whole genome sequencing technology, which is able to detect all chromosomal aberrations for UC diagnoses. Methods: UC patients and control group are prospectively recruited in trial NCT03998371. First-morning-voided urine were freshly collected before TURBT or cystectomy. Urine Exfoliated Cells DNA was analyzed by illumina HiSeq X10, followed by genotyping by bioinformatics workflow UCAD. Results: 195 individuals were prospectively recruited. 121 UC patients and 67 non-tumor diseases were included in this study. 7 other malignancies as confirmed by pathological testing were excluded. Frequent chromosome copy number changes were found in cancer patients as compared non-tumor controls, including chromosome 3 gain, 17 gain, 7 gain and 9p loss used in FISH assays were found. In addition to that, chr9q loss, 8q gain, 5q loss, 17p loss, 11p loss, 1q gain, 8p loss, 10q loss, 6q loss, 4q loss and 11q loss were also frequent in cancer patients (AUC &gt; 0.65). Metacentric chromosomes showed better AUC compared to acrocentric and telocentric chromosomes (P = 1.7e-03). A novel diagnosis model UCAD was built by incorporating all the chromosomal changes. The model reached performance of AUC = 0.933. At the optimal cutoff |Z| &gt; = 3.16, the sensitivity, specificity and accuracy were 84.7%, 97.9% and 89.0% respectively. The prediction positivity was found correlated with urine microscopy visible epithelial cells (P = 0.00069), tumor invasiveness (Ta/Tis vs the other, P = 0.0048) and tumor grade (P = 0.0030), but not microscopy RBC/WBC findings, urine culture findings, smoke and drinking history. The UCAD model outperformed cytology tests by predicting all 16-cytology positive and 12 cytology negative tumors with comparable specificity. The model found 75.0% more tumors. And UCAD identified more upper urinary tract cancer (P = 0.012) and smaller tumors ( &lt; 3cm, P = 5.9e-04). The adding of cytology to UCAD did not improve diagnosing sensitivity and specificity. UCAD reproduce the diagnoses among morning - void urine, morning, afternoon urine samples with correlation coefficient R 2 &gt; 0.98. All the urine samples showed high concordances with matched tumor samples (R 2 &gt; 0.85). Conclusions: UCAD could be a high specific, robust UC diagnoses method with improved sensitivity as compared to cytology tests. Clinical trial information: NCT03998371.