tbuckley/cabot-search huggingface dataset:
Eric Bywaters a life story: 1 June 1910 to 2 April 2003
Authors: David Isenberg
Journal: Annals of the Rheumatic Diseases (2020)

In the early 1990s I regularly attended the Executive and Finance Committee of the charity then known as the Arthritis Research Campaign and was delighted to have the opportunity to meet and talk to Eric Bywaters (figure 1), widely acknowledged as one of the great innovators in British Rheumatology. 1 An early interest in biology at school in Kent led to his entering the now defunct Middlesex Hospital Medical School, from which he qualified in 1933 with a gold medal in pathology. He researched aspects of cartilage structure and function with Sir Charles Dodds at the Courtauld Institute (linked to the Middlesex Hospital) and came to the notice of one of the leading lights of rheumatology in the USA, Walter Bauer, who suggested that if he came to the Massachusetts General Hospital in Boston to work with him, he could move from studying cartilage metabolism in rabbits to that in large cows! This was enough to persuade him to spend about 2 years working in Dr Bauer’s laboratory. While there, he also studied patients with systemic lupus erythematosus, assisted by his wife Betty.



Figure 1 
Eric Bywaters in his heyday!.



It was certainly this period which sparked his interest in rheumatology—a subspeciality then barely recognised in the UK. In 1939 with the outbreak of the Second World War imminent, he and his wife moved back to London, where he took over a run-down hospital ward at the Hammersmith Hospital, then part of the …
Immunological predictive and prognostic factors in patients with stage II-III triple negative breast cancer.
Authors: Olga Gordeeva, Irina Vladimirovna Kolyadina, Antonina Chertkova, Esma Shoua, Zaira Kadagidze, Elena Slavina, Tatiana Zabotina, Yana Vishnevskaya, Inna Ganshina, Lyudmila Zhukova, Andrey Meshcheryakov
Journal: Journal of Clinical Oncology (2020)

e12581 Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Pathologic complete response (pCR) achievement during neoadjuvant chemotherapy (NACT) is very important for these pts as it correlates with long-term outcome. Predictive and prognostic factors for this group of pts are needed. Methods: Since 2014 we treated 98 pts with histologically confirmed stage II-III TNBC with following regimen of NACT: 6 cycles of Cisplatin 75mg/m2 day 1 and Paclitaxel 80mg/m2 days 1, 8, 15, every 4 weeks according to local protocol. After NACT pts proceeded to radical breast surgery with assessing of pathological response. Before the treatment we assessed TILs in biopsy samples of all patients. We also conducted subpopulation analysis of lymphocytes in peripheral blood before treatment. We analyzed CD8 + , CD25 + , NK and NKT cells as they were reported to be significant earlier. We compared results with median value in reference group (mRG) of healthy women. Results: Among all 98 pts 86 (87%) were operated, pCR was achieved in 60,5% of operated pts. pCR strongly correlated with TILs level: 38,5% for pts with TILs &lt; 5% and 69,8% for pts with TILs &gt; 5% (p = 0,05). We also found that NKT population was associated with pCR: 77,8% vs 45,8% among patients with NKT above mRG and up to mRG, respectively (p = 0,01). It correlated also with tpCR: 22,2% vs 70,6% (p = 0,01). When both CD25 + and NKT population were above mRG pCR rate achieved in 85,7% pts vs 50,0% pts if it was up to mRG (p = 0,049). NK, CD8 + and CD25 + did not show any correlation with pCR. Survival results are presented in table below. NK, NKT and TILs did not show any correlation with survival. Interestingly, CD8 + were also associated with lower incidence of visceral metastases: 42,1% in pts with normal CD8 + and 15,7% in pts with CD8 + above normal (p = 0,19). Conclusions: Not only TILs, but also NKT and CD25 + /NKT population in the peripheral blood could be possible predictive factors for patients with stage II-III TNBC receiving NACT. CD8 + , CD25 + and NKT populations could be further studied as prognostic markers for this group of patients. [Table: see text]
Keep blood sugar level under control to prevent chronic diabetic complications
Authors: 陆菊明
Journal: BMJ (2007)

随着对糖尿病病理生理和自然规律的深入研究,现已明确糖尿病的自然发展是胰岛功能不断走向衰竭,同时持续伴有胰岛素抵抗的过程.因此,糖尿病非但不能治愈,而且随着病程的延长,还需要不断调整治疗措施,才能将血糖控制在理想范围内。
Addressing rural disparities in cancer care via telehealth.
Authors: Laurence J. Heifetz, Ahrin B. Koppel, Elaine M Kaime, Daphne Palmer, Thomas John Semrad, Primo Lara, Richard J. Bold
Journal: Journal of Clinical Oncology (2020)

e19090 Background: Patients in rural areas have reduced access to high-quality cancer care, which contributes to rural-urban disparities in cancer mortality. Telehealth technologies can connect providers across rural and urban communities. Methods: In 2006, one author (LH) established an oncology program in Truckee, CA, a rural community with a single critical access hospital without oncology services. The program joined with 4 other facilities comprising the UC Davis Cancer Care Network, a central element being daily participation in structured virtual tumor boards addressing the four sites (colorectal, prostate, lung, &amp; breast) that compromise ~80% of all cancer diagnoses. Remote telemedicine clinics outside the primary catchment area were also established to serve the mountain communities of Quincy, Portola, Loyalton, and South Lake Tahoe, CA. We assessed the reach and quality of the cancer program through referrals, in-migration, clinical trial accruals and accreditations. Results: The combination of virtual tumor boards and telehealth clinics associated with growth of the program to 3 medical oncologists, 1 radiation oncologist and expansion into a 20,000 ft 2 facility. Total new patient visits, the percent of patients coming from zip codes outside of the primary catchment area, clinical trial enrollments, and quality accreditations steadily increased (Table). The program is accredited by the Commission on Cancer with commendation, ASTRO’s APEX, ASCO’s QOPI and CancerLinq programs, and is a G0 2 Foundation for Lung Cancer Community Center of Excellence. Conclusions: We termed the knowledge dissemination that occurs through a telehealth connected rural oncology program involving a Comprehensive Cancer Center partner and disseminated rural telemedicine nodes a “synaptic knowledge network.” In this implementation, it enhanced the reach and quality of care as measured by volume, in-migration, clinical trial activity, and national quality accreditations. Application of synaptic knowledge networks to other rural sites is a promising strategy to reduce rural-urban disparities in cancer care. [Table: see text]
Vigorous intensity exercise is essentially safe for coronary heart disease patients
Authors: Swain David, 武德崴, 吴永健
Journal: BMJ (2012)

Context Aerobic exercise is beneficial for the prevention and treatment of coronary heart disease (CHD). Prescribing such exercise involves frequency, intensity, duration and total volume. Regarding intensity, the question of safety is often raised. Increased sympathetic drive during exercise increases clotting and ventricular excitability, and can trigger coronary events. Acute vigorous intensity exercise significantly increases the risk of myocardial infarction (MI) and cardiac arrest. Chronic vigorous intensity exercise increases aerobic capacity and reduces the risk of CHD more than moderate intensity. Research in Norway has demonstrated superior patient benefits of vigorous versus moderate intensity training. In consequence, these rehabilitation centres have adopted vigorous intensity training. Rognmo and colleagues evaluated the safety of this practice.
Meta-analysis of efficacy and safety of application of adjuvant materials in the repair of anterior vaginal wall prolapse
Authors: Min Hu, Bing-shu Li, Yan-xiang Cheng, De-bin Wu, Jie Min, Wen-juan Ding, Sha-sha Hong, Li Hong
Journal: BMJ (2012)

Objective To search the literature of randomized controlled trials on the treatment of anterior vaginal wall prolapse with adjuvant materials and compare the efficacy and safety of anterior vaginal wall prolapse repair with and without adjuvant materials.Methods Searches were made in the databases of Pubmed,Embase and Ovid for randomized controlled trials from 1980 to 2012 on the treatment of anterior vaginal wall prolapse with adjuvant materials.Comprehensive meta-analyses were conducted with Revman 5.1 analysis software to compare vaginal wall anatomy failure rate,operative duration,intraoperative bleeding volume,postoperative visceral injury,pelvic pain,urinary infection,material exposure,material erosion,de novo urinary incontinence and de novo dyspareunia in the adjuvant materials repair and repair without adjuvant materials groups.Results A total of 20 randomized controlled trials including 2313 participants were retrieved.The shortest average follow-up period was 3 months and the longest 36 months.Compared with repair without adjuvant materials,the application of adjuvant materials in anterior vaginal wall repair reduced vaginal front wall prolapse anatomy failure rate lower anatomy failure rate,had a longer operating duration,more peri-operative bleeding and lower urinary tract infection rate.The comprehensive effects were as follows:P＜0.01,RR =0.51,95％CI:0.41-0.64;P ＜0.01,weighted mean differenece (WMD) =16.25,95％ CI:8.07-24.43;P =0.01,WMD =35.00,95％ CI:6.90-63.11 ;P =0.03,RR =0.51,95％ CI:0.28-0.93,respectively,but the comparison of two groups around in visceral injury,postoperative pain,de novo stress urinary incontinence and de novo dyspareunia had no significant differences (P =0.07,0.58,0.54 and 0.67) and the average materiale exposure and rosion rate were 4.37％ (27/618) and 7.69％ (24/312) respectively.Conclusions The application of adjuvant materials in anterior vaginal wall repair can improve the postoperative recurrence.But no obvious differences exist in the incidence of complications in anterior repair with adjuvant materials and repair without adjuvant materials.

Key words: 
Uterine prolapse; Equipment and supplies; Meta-analysis
Somatic alterations of <i>NF1</i> in colorectal cancer.
Authors: Hiroyuki Arai, Andrew Elliott, Joanne Xiu, Jingyuan Wang, Francesca Battaglin, Shivani Soni, Wu Zhang, Davendra Sohal, Richard M. Goldberg, Michael J. Hall, Aaron James Scott, Mohd Khushman, Jimmy J. Hwang, Emil Lou, Benjamin A. Weinberg, John Marshall, Albert Craig Lockhart, Anthony Frank Shields, W. Michael Korn, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2020)

4066 Background: NF1 encodes neurofibromin, which is a key GTPase-activating protein that downregulates RAS activation. Inactivating mutations in NF1 result in sustained activation of RAS signaling, a key driver for development of colorectal cancer (CRC), and have been suggested to be a potential mechanism of resistance to EGFR inhibition in RAS-wild type (WT) CRC. Little is known about molecular characteristics of NF1-mutated (MT) CRC. Methods: Tumor profiles from 8150 CRC patients (pts) with available NF1 mutation status were retrospectively reviewed. NextGen sequencing by a customized 592-gene panel was performed. Microsatellite instability (MSI) / mismatch repair (MMR) status, tumor mutational burden (TMB) and PD-L1 expression were tested. Molecular profiles between NF1-MT and NF1-WT pts were compared. Results: Out of 8150 pts, 176 (2.2%) had somatic NF1 mutations with pathogenic or presumed pathogenic function. A higher NF1-MT frequency was observed in MSI-H/dMMR vs MSS/pMMR (13.5% vs 1.4%, p &lt; 0.0001), in right-sided vs left sided (2.9% vs 1.8%, p &lt; 0.01), and in RAS-WT vs RAS-MT (3.0% vs 1.4%, p &lt; 0.0001). In MSS/pMMR tumors, no association with sidedness was observed (right: 1.3% vs left: 1.2%, NS). The most prevalent co-mutations with NF-1 were APC (63.2%), ARID1A (57.5%), TP53 (51.5%), KMT2D (32.9%) and KRAS (32.4%) in all cases, and APC (76.2%), TP53 (69.5%), KRAS (38.8%), ARID1A (34.4%) and FBXW7 (21.5%) in MSS/pMMR cases. POLE mutation was observed in 18.4% of NF1-MT/MSS/pMMR pts. Compared to NF1-WT pts, NF1-MT pts had more frequent mutations in ARID1A (All: 57.5% vs 23.3%, p &lt; 0.0001; MSS/pMMR: 34.4% vs 15.2%, p &lt; 0.05), and less frequent mutations in KRAS (All: 32.4% vs 49.0%, p &lt; 0.0001; MSS/pMMR: 38.8% vs 50.3%, p &lt; 0.05). Also, NF1-MT pts had more frequent alterations in homologous recombination pathway compared to NF1-WT pts (All: 39.8% vs 7.5%, p &lt; 0.0001; MSS/pMMR: 17.5% vs 4.4%, p &lt; 0.0001). Mean TMB was significantly greater in NF1-MT than NF1-WT (All: 48.9/Mb vs 10.0/Mb, p &lt; 0.0001; MSS/pMMR: 48.3/Mb vs 8.2/Mb, p &lt; 0.0001). Also, PD-L1 positivity was higher in NF1-MT compared to NF1-WT (All: 12.9% vs 3.6%, p &lt; 0.0001; MSS/pMMR: 7.1% vs 2.6%, p &lt; 0.05). Conclusions: While more frequent than in RAS-MT pts, NF1-MT CRC was a small subset in RAS-WT pts. NF1-MT was associated with alterations in chromatin remodeling and DNA damage response pathways, as well as elevated TMB and PD-L1 expression, which may provide alternative therapeutic strategies beyond EGFR inhibition.
Circulating tumor DNA to monitor treatment response and investigate resistance mechanism in BRAF inhibitor treated colorectal cancer patients.
Authors: De-Shen Wang, Yu-Hong Li, Hua Bao, Xiaoxi Chen, Ming-Tao Hu, Ting Li, Hui Yang, Huai-Qiang Ju, Xue Wu, Yang Shao, Rui-hua Xu
Journal: Journal of Clinical Oncology (2020)

e16112 Background: BRAF mutations are found in about 10% of colorectal cancer (CRC) patients and is a poor prognosis factor in standard chemotherapy. Combination of BRAF and EGFR inhibition exerts a better therapeutic effective, whereas the resistance develops through undefined mechanisms. Circulating tumor DNA (ctDNA) is a non-invasive approach to assess the genetic evolution of tumors and prognosis in response to therapy, which would help better understanding the treatment response and resistance mechanism in BRAF inhibitor treated colorectal cancer patients. Methods: We performed panel next-generation sequencing of 425 cancer-related genes in 39 serial plasma samples collect from 19 patients who have BRAF V600E mutation CRC to track the resistance during the Vemurafenib treatment in combination with Irinotecan and Cetuximab (VIC) and evaluate the treatment response. Tumor responses were assessed radiologically every two months and are used to determine patients with innate or acquired resistance Results: A total of 19 patients were enrolled into the vemurafenib treatment with irinotecan and cetuximab. By January 20, 2020, treatment had been discontinued in 12 (63.2%) of the patients due to disease progression, while the other 7 cases were still under treatment. Among them, four patients with innate resistance (n = 4, 21.1%) were defined as those with PFS of less than 2 months, while patients (n = 15, 78.9%) with acquired resistance were defined as those with PFS of greater than 2 months. The VIC regimen demonstrated efficacy in patients with BRAF-mutant mCRC, with overall response rates was 63.2% (n = 12). Changes in levels of ctDNA at 4 weeks predicts therapeutic responses. CBLB, TP53 and APC baseline mutations were enriched in baseline samples of innate resistant patients. In contrast, MYC and Cell-cycle pathway alterations were enriched in baseline samples of patients with acquired resistance. Acquired RAS and MAPK mutations, known to confer resistance to BRAF inhibitors, were identified in 60% of acquired resistance patients. Moreover, acquired TGFBR2 and SMAD4 loss-of-function mutations were identified as novel resistant mechanism to the combination of BRAF and EGFR inhibition. Experimental validation is ongoing. Conclusions: Longitudinal analysis of ctDNA in BRAF CRC patients provides insights of molecular difference between innate and acquired resistance and gene alternation during resistance requiring. Serial ctDNA monitoring provides early indication of response to BRAF inhibitor in CRC patients.
Assessment of Language and Indexing Biases Among Chinese-Sponsored Randomized Clinical Trials
Authors: Yuanxi Jia, Doudou Huang, Jiajun Wen, Yehua Wang, Lori Rosman, Qingkun Chen, Karen A. Robinson, Joel J. Gagnier, Stephan Ehrhardt, David D. Celentano
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Language and indexing biases may exist among Chinese-sponsored randomized clinical trials (CS-RCTs). Such biases may threaten the validity of systematic reviews. <h3>Objective</h3> To evaluate the existence of language and indexing biases among CS-RCTs on drug interventions. <h3>Design, Setting, and Participants</h3> In this retrospective cohort study, eligible CS-RCTs were retrieved from trial registries, and bibliographic databases were searched to determine their publication status. Eligible CS-RCTs were for drug interventions conducted from January 1, 2008, to December 31, 2014. The search and analysis were conducted from March 1 to August 31, 2019. Primary trial registries were recognized by the World Health Organization and the Drug Clinical Trial Registry Platform sponsored by the China Food and Drug Administration. <h3>Exposures</h3> Individual CS-RCTs with positive vs negative results (positive vs negative CS-RCTs). <h3>Main Outcomes and Measures</h3> For assessing language bias, the main outcome was the language of the journal in which CS-RCTs were published (English vs Chinese). For indexing bias, the main outcome was the language of the bibliographic database where the CS-RCTs were indexed (English vs Chinese). <h3>Results</h3> The search identified 891 eligible CS-RCTs. Four hundred seventy CS-RCTs were published by August 31, 2019, of which 368 (78.3%) were published in English. Among CS-RCTs registered in the Chinese Clinical Trial Registry (ChiCTR), positive CS-RCTs were 3.92 (95% CI, 2.20-7.00) times more likely to be published in English than negative CS-RCTs; among CS-RCTs in English-language registries, positive CS-RCTs were 3.22 (95% CI, 1.34-7.78) times more likely to be published in English than negative CS-RCTs. These findings suggest the existence of language bias. Among CS-RCTs registered in ChiCTR, positive CS-RCTs were 2.89 (95% CI, 1.55-5.40) times more likely to be indexed in English bibliographic databases than negative CS-RCTs; among CS-RCTs in English-language registries, positive CS-RCTs were 2.19 (95% CI, 0.82-5.82) times more likely to be indexed in English bibliographic databases than negative CS-RCTs. These findings support the existence of indexing bias. <h3>Conclusions and Relevance</h3> This study suggests the existence of language and indexing biases among registered CS-RCTs on drug interventions. These biases may distort evidence synthesis toward more positive results of drug interventions.
Abstract 18128: Phenome-Wide Association Study of Familial Hypercholesterolemia Variants Among Multi-Ethnic Veterans
Authors: Yan V Sun, Scott M Damrauer, Qin Hui, Themistocles L Assimes, Yuk-Lam Ho, Pradeep Natarajan, Derek Klarin, Jie Huang, Julie A Lynch, Scott L DuVall, Jacqueline P Honerlaw, Kelly Cho, Daniel J Rader, Christopher J O’Donnell, Philip S Tsao, Peter W Wilson
Journal: Circulation (2017)

Introduction: Familial hypercholesterolemia (FH), characterized by severely elevated levels of low-density lipoprotein cholesterol (LDL-C) and consequently premature coronary heart disease (CHD), i...
Radiogenomics for the prognosis in advanced non-small cell lung cancer patients receiving bevacizumab.
Authors: Butuo Li, Chao Jiang, Linlin Pang, Bingjie Fan, Mingjun Ding, Xindong Sun, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2020)

e21669 Background: In the new era of immunotherapy, the regimen based on bevacizumab is still one of the standard options for treatment of advanced non-small cell lung cancer (NSCLC) patients without driver mutations. However, the prognostic factors for bevacizumab are still missing. We aimed to determine the integrative value of computed tomography (CT), epigenetic modifications, clinicopathological and systemic inflammatory factors for predicting the survival of advanced NSCLC patients with bevacizumab. Methods: Clinicopathological parameters, dynamic systemic inflammatory factors, radiomics features, and DNA methylation profiling in advanced non-squamous NSCLC patients receiving first- or second- line bevacizumab plus chemotherapy were included in this study. The prognostic radiomics signature were constructed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A multi-omics prediction nomogram for progression-free survival (PFS) based on radiomics, clinicopathological and systemic inflammatory features was established and independently validated. Furthermore, radiomics signature-related DNA methylation were submitted to functional enrichment analysis. Results: Total of 272 patients were included in analysis, 224 in training cohort and 48 in validation cohort. Five radiomics features, including Information Measure Corr1, Inverse Variance, Local Std Max, Gauss Area, Spherical Disproportion, were finally selected to construct radiomics signature with the AUC of 0.71. Smoking history, anatomical feature, liver metastasis, LDH4, NLR2 and radiomics signature were found to be independent prognostic factors for PFS. A multi-omics nomogram was developed based on these features in training cohort with the C-index of 0.76, and external validated with the C-index of 0.75. The tissue slices of 20 patients receiving bevacizumab were used for DNA methylation profiling. Functional enrichment analysis indicated widespread and statistically significant associations between radiomics features and DNA methylation changes which involved in several pathways related to angiogenesis and immune system, such as Notch signaling pathway, small GTPase Rho signal transduction, TGFβ signal transduction. Conclusions: This multi-omics nomogram integrating radiomics, clinicopathological, systemics inflammatory features improved the prediction of PFS in advanced NSCLC patients receiving bevacizumab. And the radiomics signature were found to be related to angiogenesis and immune status.
室性心动过速的心电图表现
Authors: 刘健, 徐冷楠, 王伟民
Journal: BMJ (2009)

室性心动过速简称室速,是指起源于心室、自发、连续3个或3个以上、频率大于100次/min的期前搏动组成的心律.室速可发生于任何器质性心脏病的患者,也可发生在没有器质性心脏病的患者.冠心病、心肌病是最容易发生室速的器质性心脏病.发生在无器质性心脏病患者的室速称为特发性室速。
Objective structured clinical examination in assessment for clinical competencies of trainees in standardized training for general practice at its completion in Shanghai
Authors: Sun-fang Jiang, Juan Shou, Xiang-jie Zhang, Ming-hui Peng, Shan-zhu Zhu
Journal: BMJ (2009)

Objective To set up methods for objective structured clinial examination(OSCE)for its application in assessment for clinical competencies of trainees in standardized training for general practice at its completion in Shanghai.Methods Trainees in standardized training for general practice in Shanghai were assessed at its completion in July 2009 at Zhongshan Hospital of Fudan University,which was organized and implemented by establishment of OSCE management framework and design of assessment stations,including writing-up medical records for cases,training standardized patients,selecting assessment itemsfrom checklists of clinical skills.as well as working-out a form for assessment scoring.Results Six assessment stations were set up for OSCE,including clinical data collection,medical record writing,case analysis,clinical skills,diagnostic decision-making based on electrocardiograms(ECGs)and x-ray films.Totally,32 trainees took part in OSCE and all passed examination.Score of medical record writing Was higher than that of clinical data collection [86(IQR 74-91)vs.79(IQR 67-85),P＜0.05].There was no significant difference in scores between medical reeord writing and case analysis [86(IQR 74-91)vs.80(IQR 73-86),P＞0.05].Score of X-ray film diagnosis Was higher than that of ECG diagnosis and clinical skills[99(IQR 96-100) vs.95(IQR 91-98),and 99(IQR 96-100)vs.90(IQR 83-94),all P＜0.01].Conclusions Clinical competeneies of trainees of general practice Can be assessed by OSCE in multiple aspects,which provides a new examination method for GP training.

Key words: 
Training;  Objective structured clinical examination(OSCE);  Clinical skills