tbuckley/cabot-search huggingface dataset:
Platform comparison of HTG EdgeSeq and RNA-Seq for gene expression profiling of tumor tissue specimens.
Authors: Di Ran, Janhavi Moharil, James Lu, Heather Gustafson, Kerry Culm-Merdek, Kristen Strand-Tibbitts, Laura Benjamin, Marian Navratil
Journal: Journal of Clinical Oncology (2020)

3566 Background: Clinical biomarker studies are often hindered by the availability of tissue specimens of sufficient quality and quantity. While RNA-Seq is often considered the gold standard for measuring mRNA expression levels in cancer tissue, it typically requires multiple formalin-fixed paraffin-embedded (FFPE) tissue sections to extract a sufficient amount of quality RNA for subsequent gene expression profiling analysis. The HTG EdgeSeq technology is a gene expression profiling platform that combines quantitative nuclease protection assay technology with next-generation sequencing detection. Unlike RNA-Seq, the HTG EdgeSeq technology does not require RNA extraction, and can use small amounts of tissue material, typically several mm 2 , to generate reproducible gene expression profiles. Methods: This study compares the performance of RNA-Seq and HTG's profiling panel, the HTG EdgeSeq Precision Immuno-Oncology Panel (PIP), which is designed to measure expression levels of 1,392 genes focused on tumor/immune interaction. Approximately 1,200 samples from three tumor indications (gastric cancer, colorectal cancer and ovarian cancer) were tested using both technologies. Results: Up to four FFPE slides were used for RNA extraction to support RNA-Seq testing; out of the 1,202 samples processed, 1,099 generated extracted RNA of sufficient quality and quantity (as measured by RNA concentration, RIN score and %DV200) to proceed to sequencing, which resulted in a pass rate of 91.4% for RNA-Seq. The HTG EdgeSeq PIP panel resulted in a pass rate of 97.3% (samples passing QC metrics) when the same 1,200 samples were tested, and required only a single FFPE section owing to the small sample requirement. The t-SNE (a non-linear dimensionality reduction method) analysis of the common 1,358 genes revealed similar clustering of the three cancer indications between the two methods. Correlations across individual genes by sample resulted in the mean Spearman correlation coefficient of 0.73 (95% confidence interval of 0.61 - 0.80). Additionally, gene-wise comparisons across all samples were also evaluated. Conclusions: These data demonstrate that HTG EdgeSeq gene expression panels can be used as a competitive alternative to RNA-Seq, generating equivalent gene expression results, while offering the added benefits of a small sample size requirement, lack of RNA extraction bias, and fully automated data analysis pipeline.
Abstract 2983: Sex Differences in Quality of Life and Health Status in the COURAGE Trial
Authors: Paul Kolm, William E Boden, John A Spertus, David J Maron, Robert O’Rourke, Marcin Dada, Wei Zhang, Pamela M Hartigan, William S Weintraub
Journal: Circulation (2007)

Purpose: The Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial randomized 2,287 patients to percutaneous coronary intervention (PCI) plus optimal medical treatment (OMT) or OMT alone. The purpose of this study was to assess sex differences in quality of life (QOL) and health status between randomized initial management strategies over the trial follow-up period. Methods: Of the 2,287 patients, 979 males and 169 females were randomized to PCI, and 968 males and 169 females were randomized to OMT. Quality of life was assessed with the Seattle Angina Questionnaire (SAQ) and health status with the RAND-36 at baseline, 1, 3, 6, 12 months and annually thereafter. SAQ and RAND-36 scores were assessed by analysis of variance (ANOVA), and linear mixed effects models. Results: There were no significant sex by treatment group interactions indicating PCI vs. OMT differences were similar for the 1,947 men (85%) and 338 women (15%). Men had significantly higher SAQ Physical Functioning scores at baseline and 1 month post-treatment (p &lt; 0.004) and a trend of higher means thereafter (Figure 1A ) and significantly higher RAND-36 Physical Functioning scores over 3 years of follow-up (p &lt; 0.001, Figure 1B ). Men also had significantly higher RAND-36 Energy/Fatigue means scores (p &lt; 0.05, Figure 1C ). RAND-36 scores for the other domains were similar fbetween the two groups (Figure 1D ). Conclusions: Men and women in both arms experienced improvement in quality of life and health status over time. Men had significantly higher physical functioning as well as energy/fatigue scores, but were similar to women in other quality of life and health status domains.
<i>FLT1</i> amplification predicts poor response in metastatic colorectal cancer patients treated with apatinib as 3rd line treatment.
Authors: Ma Dong, Dongyang Yang, Fei Xu, Xiaorong Lai, Han Han-Zhang, Chunxiang Chen, Lin Shao, Shuyin Chen, Lu Zhang
Journal: Journal of Clinical Oncology (2020)

e16033 Background: Apatinib, a selective vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor, has demonstrated encouraging anticancer activity across a broad range of malignancies. Recent studies have shown efficacy of apatinib as a third-line treatment for patients with refractory colorectal cancer. In this study, we characterized the genomic profile and explored predictive and prognostic biomarkers in metastatic colorectal cancer (mCRC) patients treated with apatinib as the 3 rd line treatment. Methods: We retrospectively recruited 19 mCRC patients, with a median age of 53, treated with apatinib as the third-line regimen. The cohort consisted of 10 female and 9 male patients with 13 and 6 patietns with left-seide and right-sided CRC, respectively. Tissue samples prior to apatinib treatment were profiled using a 520-cancer-related gene panel. Results: This cohort achieved an ORR of 16% (3/19) and DCR of 53% (10/19). The median PFS and OS were 5 and 8.7 months, respectively, comparable with published studies. The genomic profile of 19 patients showed that 57% of alterations were missense, and 18% and 12% were copy number variations (CNV) and frameshift, respectively. All 19 patients were microsatellite stable (MSS). Most frequently mutated genes were TP53 (95%), APC (53%) and KRAS (53%). Other commonly mutated genes included PI3KCA (26%), FAT3 (16%), LPR1B (16%), FLT1(16%), SAMD4 (16%), TCF7L2 (16%) and TCNNB1 (16%). Univariate Cox analysis revealed a shorter PFS in patients harboring FLT1 amplification (n = 3) versus those without (P = 0.0007). All 3 patients with FLT1 amplification had progressive diease as their best response, with an average PFS of 1.4 months. Furthermore, we also revealed that APC mutation was significantly associated with older age (P = 0.02) and lymph node metastasis (P = 0.01). Patients with pulmonary metastasis were more likely to have TP53 disruptive mutation (P = 0.02). Conclusions: Our study explored the potential predictive biomerkers for apatinib and revealed that FLT1 amplification might be a potential predictive biomarker for poor efficacy in mCRC patients treated with apatinib. FLT1 encodes VEGFR1, which could compete with VEGFR2 for binding with VEGF, potentially explaining the inferior response to apatinib observed in pateints harboring FLT1 amplification. Larger cohorts are needed to validate the finding.
Clinical features of autoinflammatory diseases in 3 patients
Authors: Yulin Gong
Journal: BMJ (2014)

Patient one was a 19-year-old woman of periodic fever with urticaria during the first week of life.And there were typicalfacies, oligoarthritis and central nervous system involvement.She also exhibited a persistent elevation of acute phase reactants.The diagnosis of chronic infantile neurological cutaneous and articular syndrome was made.Short-term dosing of tumor necrosis factor-α receptor antagonist was administrated and was substituted by glucocorticoid and methotrexate.Another two males had an early-onset of increased acute phase reactants during inflammation attacks.One of them had recurrent fever with urticaria-like rash, arthralgia and headache.Muckle-Wells syndrome was diagnosed on basis of NLRP3 gene mutation (c.92A>T). And another had recurrent urticaria-like rash with conjunctivitis, oligoarthritis, hepatosplenomegaly and increased serum IgD.The clinical diagnosis was mevalonate-kinase deficiency.Autoinflammatory diseases should be suspected by physicians and diagnosed with a combination of phenotype and genotype.Biological agents, especially interleukin-1 antagonist, have broad prospects in the therapy of autoinflammatory diseases.


Key words: 
Autoinflammatory diseases; Syndrome
Increasing incidence of asbestosis worldwide, 1990–2017: results from the Global Burden of Disease study 2017
Authors: Meng Yang, Dongming Wang, Shiming Gan, Lieyang Fan, Man Cheng, Linling Yu, Bin Wang, Wei Li, Jixuan Ma, Min Zhou, Weihong Chen
Journal: Thorax (2020)

Global incidence and temporal trends of asbestosis are rarely explored. Using the detailed information on asbestosis from the Global Burden of Disease (GBD) 2017, we described the age-standardised incidence rate (ASIR) and its average annual percentage change. A Joinpoint Regression model was applied to identify varying temporal trends over time. Although the use of asbestos has been completely banned in many countries, the ASIR of asbestosis increased globally from 1990 to 2017. Furthermore, the most pronounced increases in ASIR of asbestosis were detected in high-income North America and Australasia. These findings indicate that efforts to change the asbestos regulation policy are urgently needed.
A survey on double-preceptor system in standardized residency training of general practitioners
Authors: Rong Zhou, Zhigang Pan, Qian Chen, Xiangjie Zhang
Journal: BMJ (2014)

Objective
To survey the double-preceptor system in standardized residency training of general practitioners(GPs).


Methods
A questionnaire survey was conducted among 48 residents, 53 clinical and community preceptors during May and June 2013.


Results
The preceptors mostly agree with the necessity to carry out double-preceptor system. 82.8%(24/29) clinical preceptors, 95.8%(23/24)community preceptors and 89.6%(43/48) residents considered that it was very effective.Less than half of the clinical(13/29)and community(11/24)preceptors knew very clearly about their responsibilities and obligations; 93.1%(27/29)clinical preceptors and 95.8%(23/24)community preceptors hoped to receive corresponding training courses.72.4%(21/29)clinical preceptors and 75.0%(18/24)community preceptors communicated with residents frequently, 75.9%(22/29)clinical preceptors thoughtresidents were not actively involvedwas the main obstacle in the implementation of double-preceptor system.The guide contents were focused on clinical skills, scientific research and how to pass assessments.The main approaches were interviews, checking the quality of medical instruments and small lecture.Only 6.9%(2/29)clinical preceptors conducted outpatient teaching, 83.3%(40/48)residents thoughttutors did not knew clearly about their responsibilities and obligationswas the main obstacle in the practice of double-preceptor system.Regarding how to evaluate the double-preceptor system, clinical and community preceptors tended to use examination results and feedback of residents.Clinical preceptors, community preceptors and residents all gave low comments about the preceptor-resident contact handbook. 87.5%(21/24) community preceptors thoughtlack of corresponding incentive mechanismswas the main obstacle in the practice of double-preceptor system.


Conclusions
Double-preceptor system has been widely recognized by both preceptors and students.In order to improve the system, we should conduct tutor training courses regularly and establish an effective mechanism to assess and evaluate tutors.


Key words: 
General practitioner; Preceptorship; Questionnaires
由病例分析看重症系统性红斑狼疮的诊断与治疗
Authors: 张烜
Journal: BMJ (2006)

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种可累及多器官、多组织的自身免疫病,其预后与受累脏器的严重程度以及治疗有关.治疗主要药物为糖皮质激素和免疫抑制剂,但应用时应密切注意药物的副作用,尤其是继发感染.重症SLE患者通常病情活动伴有脑肾等重要脏器受累,又同时出现严重感染,我们通过具体病例分析来介绍这种重症SLE的诊断和治疗。
Administration of dinoprostone suppositories in induced labor for full-term pregnant women with hypertensive disorders
Authors: Xuedong Tang
Journal: BMJ (2014)

Objective
To evaluate the administration of dinoprostone suppositories in induced labor for full-term pregnancy women with hypertensive disorders.


Methods
One hundred and nine full-term pregnant women admitted in Jiaxing Maternal and Child Health Care Hospital from February 2010 to December 2011 were included in the study. The subjects included 43 cases with pregnant hypertension (group A), 36 cases with mild preeclampsia (group B), 30 cases with severe preeclampsia (group C), and 30 full-term normal puerpera were also included (group D). Dinoprostone suppositories were placed in the vagina for induction. The cesarean delivery rate and perinatal prognosis were compared among the four groups.


Results
The cesarean delivery rate in group C was higher than other 3 groups; there was no significant difference among groups A, B and D. The rates of fetal distress and postpartum hemorrhage in group C were higher than those in other 3 groups; there were no significant differences in rates of fetal distress and postpartum hemorrhage among group A, B and D, while there was no difference in rate of neonatal asphyxia among all groups.


Conclusion
Dinoprostone is effective and safe in inducing labor for full-term pregnancy women with hypertensive disorders.


Key words: 
Dinoprostone; Hypertension, pregnancy-induced; Labor, induction
GEN-009, a neoantigen vaccine containing ATLAS selected neoantigens, to generate broad sustained immunity against immunogenic tumor mutations and avoid inhibitory peptides.
Authors: Roger B. Cohen, Przemyslaw Twardowski, Melissa Lynne Johnson, Maura L. Gillison, Mark N. Stein, Ulka N. Vaishampayan, Lisa McNeil, Mara Shainheit, Daniel DeOliveira, Manish Jain, Jessica Price, Richard Hernandez, Arthur P. DeCillis, Narinderjeet Singh, Jessica Flechtner, Thomas A. Davis
Journal: Journal of Clinical Oncology (2020)

3107 Background: Tumor-specific neoantigens provide personalized targets for immunotherapy. Vaccines against epitopes predicted by in silico approaches very rarely induce CD4 + and CD8 + ex vivo T cell responses regardless of formulation. ATLAS selects neoantigens for vaccine inclusion using ex vivo screening of all patient-specific mutations to identify pre-existing CD4 + or CD8 + T cell responses and to exclude Inhibigens, which are inhibitory peptides that suppress immunity and accelerate tumor progression. The Inhibigen burden correlates with patient outcomes in observational studies and rapid tumor progression in mouse models. Methods: GEN-009-101 is a phase 1/2a study testing safety, immunogenicity and clinical activity in immune responsive tumors. After next-generation tumor sequencing and ATLAS testing of autologous leukocytes, up to 20 stimulatory synthetic long peptides adjuvanted with poly-ICLC comprise each personalized vaccine. Eight vaccinated patients have been followed for sustained immunological responses and clinical outcomes. Results: The 40 doses given across patients have induced only mild local discomfort and no DLT. Vaccination has generated immune responses against 99% of administered peptides, with both CD8 + and CD4 + responses in ex vivo fluorospot assays. To date, no patients have developed recurrent disease. Broad immunity develops as early as Day 29 and is sustained for over 12 months. Immune response against individual peptides is correlated with peptide concentration (OR = 1.26, p≤0.0001) but not with other classifiers such as GRAVY index (Grand Average of Hydropathy), tumor type, injection site or sex. The Inhibigen burden prior to treatment again correlates with disease progression. Conclusions: GEN-009 identifies tumor specific immune targets from the individual patient’s tumor mutagens. Initial clinical data show that ATLAS antigen selection may be critical to the induction of broad, rapid and sustained immunity against tumor specific neoantigens. Clinical vaccination with PD-1 blockade is in process. Clinical trial information: NCT03633110 . [Table: see text]
The Matilda effect: Under-representation of women in hematology and oncology awards.
Authors: Shruti R Patel, Frederique St-Pierre, Ana I. Velazquez Manana, Snegha Ananth, Urshila Durani, Andrea Carolina Anampa-Guzmán, Katerina Castillo, Natasha Dhawan, Kathryn Jean Ruddy, Amy S Oxentenko, Narjust Duma
Journal: Journal of Clinical Oncology (2020)

11012 Background: The proportion of women in the field of hematology and oncology (H&amp;O) has increased over recent decades, but representation by women in leadership positions remains a challenge. Our aim was to examine representation of winners of recognition awards by gender and race from the major international hematology and oncology societies. Methods: Published award recipients from the seven major H&amp;O societies were reviewed, with 26 years of data included (1994-2019). Awardee demographics and academic rank were collected and included in the analysis. Gender was determined based on awardee full name and verified by public data. Chi-square and Cochran-Armitage tests were used to analyze the data. Results: Over the past 26 years, 942 awards were presented at the 7 major H&amp;O societies. We excluded 27 gender specific awards from the analysis. Of the 915 awardees included in analysis, award recipients were overwhelmingly men (77.9%) and non-Hispanic white (84.7%). Gender breakdown by society is described in table. ESMO and ASTRO represented the lowest distribution of women at 9.1% and 11.1%, respectively. Women awardees received 30.3% of the awards categorized as humanistic and education-related, while only receiving 16.0% of awards in the basic sciences category (p&lt;0.01). The Cochran-Armitage test demonstrated an upward trend in the number of women awardees, from 10% between 1994-1998 to 25.6% between 2014-2019 (p=0.0004). Over the past five years, the average proportion of women medical oncologists was 35.6% per the AAMC. In this time period, women oncologists have received only 24.0% of all awards, suggesting the awardees included in the study period do not represent the proportion women in the field (p=0.00424). Black, Hispanic, and Asian awardees represented 3.7%, 3.3%, and 6.8% of the total awardees, respectively. Of the 64 Black and Hispanic awardees, 60.9% of the awards were for investigating healthcare disparities and only 4.6% were given for basic science research. Conclusions: During our study period, women physicians and investigators were less likely to receive recognition awards from the seven major H&amp;O societies compared to men. We also observed a considerable low proportion of minority awardees in all oncology subspecialties. While the proportion of women awardees has increased over time, significant underrepresentation remains. [Table: see text]
A retrospective analysis of post second-line chemotherapy treatment outcomes for patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions.
Authors: Milind M. Javle, Saeed Sadeghi, Anthony B. El-Khoueiry, Lipika Goyal, Philip Agop Philip, Robin Kate Kelley, Ivan Borbath, Teresa Macarulla, Wei-Peng Yong, Suebpong Tanasanvimon, Amit Pande, Gary Li, Michael Howland, Craig Berman, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2020)

4591 Background: Cholangiocarcinoma (CCA) is the most common biliary tract malignancy with an estimated incidence of 8,000–10,000 patients/year in the US. Chemotherapy is the most common second-line treatment with reported outcomes in patients with CCA. Response rates of &lt; 10% and median progression-free survival (PFS) times of ~3–4 months have been reported with second-line chemotherapy regimens, including FOLFOX in the ABC-06 trial. Fibroblast growth factor receptor 2 ( FGFR2) fusions occur in 13–17% of CCA and multiple targeted agents are in development for patients with FGFR2 fusions. To date, the outcome of patients with CCA and FGFR2 fusions receiving standard second-line chemotherapy is unknown. Methods: Patients with advanced CCA and FGFR2 fusions after prior treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase 2 study (NCT02150967) and received the FGFR1–3 selective TKI infigratinib (previously BGJ398) 125 mg orally qd on d1–21, cycles repeated q28 days until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent. A retrospective analysis of a subset of patients who received infigratinib as third- or later-line treatment was performed. Investigator-assessed PFS and best overall response (BOR, per RECIST 1.1) following second-line chemotherapy (pre-infigratinib) and third-line or later-line infigratinib were calculated. Results: Of the 71 patients (44 women; median age 53 years) with FGFR2 fusions enrolled at the time of analysis (datacut 8 August 2018), 37 (52%) were included in this retrospective analysis. Median PFS with standard second-line chemotherapy was 4.63 months (95% CI 2.69–7.16) compared with 6.77 months (95% CI 3.94–7.79) for third- and later-line infigratinib. BOR for second-line chemotherapy was 5.4% (95% CI 0.7–18.2) compared with 21.6% for third- and later-line infigratinib (95% CI 9.8–38.2). Conclusions: Outcomes from second-line chemotherapy in patients with CCA and FGFR2 fusions were similar to those reported in the literature for all patients with CCA regardless of genomic status and remain dismal. Infigratinib administered as third- and later-line treatment resulted in a meaningful PFS and ORR benefit in patients with CCA and FGFR2 fusions. Clinical trial information: NCT02150967 .