tbuckley/cabot-search huggingface dataset:
Incidence of type 1 diabetes in China, 2010-13: population based study
Authors: 翁建平, 周智广, 郭立新, 朱大龙, 纪立农, 罗小平, 母义明, 贾伟平, 代表中国 型糖尿病研究组, 王超凡
Journal: BMJ (2019)

目的
估算2010—2013年中国全年龄组人群的1型糖尿病发病率。


研究设计
基于人群的登记研究，使用多个独立来源的数据。


研究地点
中国13个地区505家提供糖尿病诊疗的公立医院登记系统、糖尿病患者社区数据，总共包括了超过1.33亿人年的风险人群，约占总人口的10%。


研究对象
2010年1月1日至2013年12月31日，研究区域常住的5 018例新诊断的1型糖尿病的全年龄段患者。


主要结局指标
按年龄、性别和研究区域分层，每10万人年1型糖尿病的发病率。1型糖尿病由医生诊断，并通过现场随访确认。确认病例收集情况的完整性采用捕获-再捕获法评估。


结果
共确认5 018例新诊断的1型糖尿病患者：1 239例年龄<15岁，1 799例年龄在15~29岁，1 980例年龄≥30岁。≥20岁新发病例的比例为65.3%。中国全年龄段人群1型糖尿病的估算发病率为1.01/10万人年（95%可信区间：0.18~1.84）。0~14岁年龄组发病率为1.93/10万人年（0.83~3.03），15~29岁为1.28/10万人年（0.45~2.11），≥30岁为0.69/10万人年（0.00~1.51），发病率高峰在10~14岁年龄组。15岁以下的发病率与纬度呈正相关（r=0.88，P<0.001），然而在15~29岁或≥30岁年龄组中未观察到这种相关性。


结论
中国大多数1型糖尿病新发病例发生在成人。本研究报道的中国儿童1型糖尿病的发病率在各研究中最低。
Unhealthy psycho-behavioral practices for weight control in adolescent students with overweight or obesity
Authors: Bian Yang, Shen Liu
Journal: BMJ (2012)

A questionnaire survey was conducted in 724 students from three junior high schools in Shanghai Jinshan district.Total 642 students completed the questionnaire with a response rate of 88.7％,among them 75 were overweighted or obese.The positive rate of 6 out 8 unhealthy psycho-behavioral practices related to weight control in overweight or obese students was significantly higher than that of students with normal weight (all P ＜ 0.05).Binary logistic backward stepwise regression analysis showed that overweight or obesity was risk factor for the unhealthy psycho-behavior practices related to weight control in adolescent students.

Key words: 
Overweight; Diet
以晕厥和急腹症为主要表现的年轻人主动脉夹层一例
Authors: 尹勇, 陈文华
Journal: BMJ (2008)

患者男,25岁.因突发晕厥伴上腹剧痛3 h人院.患者于2005年12月12日21:00无诱因突然晕倒,四肢抽搐,两眼上翻,呼之不应,约半分钟后意识恢复,诉上腹部持续性剧痛,平卧位加重,伴腰背部放射痛,呕吐2次,量少,为胃内容物。
AR enhancer and locus genomic alterations as cell-free DNA biomarkers of primary resistance to AR-directed treatment of metastatic prostate cancer.
Authors: Chris Maher, Ha X. Dang, Pradeep S. Chauhan, Haley Ellis, Wenjia Feng, Peter Harris, Grace Smith, Mark Qiao, Katherine Dienstbach, Rachel Beck, Andrew Atkocius, Faridi Qaium, Jingqin Luo, Jeff Michalski, Joel Picus, Russell Kent Pachynski, Aadel Chaudhuri
Journal: Journal of Clinical Oncology (2020)

5529 Background: Predicting primary resistance to androgen receptor (AR)-directed therapies is critical for personalizing treatment of metastatic prostate cancer (mPCa). Analyses of liquid biopsies are potential tools but remained underutilized due to limited sensitivity. We developed a cell-free DNA (cfDNA) assay (EnhanceAR-Seq) to monitor genomic alterations in mPCa including AR enhancer duplication, a resistance marker recently discovered in ~81% of mPCa patients. Here we show that applying EnhanceAR-Seq to plasma cfDNA to monitor alterations of AR gene and enhancer ( AR/enhancer) predicted primary resistance with high sensitivity and outperformed the clinically validated CTC AR-V7 assay. Methods: Forty mPCa patients were prospectively enrolled at the Washington University School of Medicine Siteman Cancer Center with plasma cfDNA analyzed by EnhanceAR-Seq. Twenty-five of them also had the Oncotype DX AR-V7 Nucleus Detect CTC assay performed at a similar timepoint at the discretion of the treating oncologist. All patients received AR-directed therapy (eg. abiraterone, enzalutamide) and underwent standard-of-care clinical and laboratory follow-up. Primary resistance was defined as PSA progression, change of treatment or death within 4 months of treatment initiation, or radiographic progression within 6 months. Results: Median clinical follow up after diagnosis was 50 months. EnhanceAR-Seq detected alterations targeting AR/enhancer in 18 patients (45%), TP53 in 8 patients (20%), and PTEN in 6 patients (15%). We found that AR/enhancer alterations (copy gain, tandem duplication, and point mutation) in cfDNA were strongly predictive of primary resistance to AR-directed therapy (PPV = 100%, Sens. = 89%). Our assay outperformed the CTC AR-V7 assay, which was positive in only two patients (PPV = 50%, Sens. = 6%). Furthermore, patients with AR/enhancer alterations had significantly worse progression-free survival (P = 0.0015; HR = 11.5) and overall survival (P = 0.0002; HR = 6.8). Finally, serial cell-free DNA analysis of 10 patients showed that AR/enhancer copy number gain was maintained or acquired in 5 of 6 AR-resistant cases, and neutrality maintained in 4 of 4 AR-sensitive cases. Conclusions: cfDNA-based AR/enhancer locus genomic alterations could potentially be used to predict primary resistance to AR-directed therapy with higher sensitivity than the clinically validated CTC AR-V7 assay, be used for serial timepoint monitoring and guiding personalized clinical decision-making.
Diagnostic strategy of primary aldosteronism based on CT scan and serum potassium level
Authors: Yu Zhang, Hai Li, Guohong Wei, Jianbin Liu, Wanping Deng, Xiaopei Cao
Journal: BMJ (2019)

One hundred and forty-five patients with primary aldosteronism (PA) admitted from 2006 to 2013 were enrolled in the study. The diagnosis of PA was confirmed by upright furosemide test and all patients met the following criteria: ① round-or oval-shaped lesion of low density with diameter>1 cm in one adrenal gland shown in contrast CT scan; ② no lesion or abnormality in contralateral adrenal gland; ③serum potassium level<3.5 mmol/L. Of 145 patients, 106 underwent total adrenalectomy, 36 partial adrenalectomy and 3 tumor enucleation. Serum potassium was (2.75±0.55) mmol/L before and (4.03±0.46) after surgery. Potassium was normalized after treatment in 141 cases (97.2%) with correction or improvement in hypertension; 4 patients (2.8%) remained hypokalemic and received spironolactone. Patients with normalized potassium were followed up for a medium period of 74 months (22—103 months), of whom 32 (22.7%) dropped off; the remaining 109 (77.3%) patients did not have hypokalemia. Multivariate linear correlation analysis showed that serum potassium level was negatively correlated with tumor diameter (r=−0.273, 95% CI:−0.086—−0.564, P=0.026) and basal serum aldosterone level (r=−0.261, 95% CI:−0.047—−0.514, P=0.036). In PA patients with unilateral adrenal macroadenoma and hypokalemia, satisfactory surgical resolution can be achieved without adrenal venous sampling in majority of patients.


Key words: 
Hyperaldosteronism, primary; Adrenal gland neoplasms; Hypokalemia; Tomography, X-Ray computed
Hierarchical hypertensionmanagement in communities
Authors: Tao Zhou, Yu-ling Cui, Pei-fen Chang, Hui Wang
Journal: BMJ (2008)

：A total of 203hypertensive patients with established health files received standard disease managementfor 1 year. We found that the patients who underwent grade 2 or 3 management showedstatistically significant difference in exercise, salt and oil restriction, body massindex (BMI), waist to hip ratio, blood pressure, and blood-lipid from baseline (all P <0.05). Hypertension awareness, behavior improvement, and disease control had statisticallysignificant difference from baseline in all the patients (P < 0.05 or P < 0.001).After one year's intervention, the patient number in each grade was largely changed. Ourstudy suggests that hierarchical hypertension management might be practical and effectivein communities.
Plasma thermogram profiling: A novel biomarker for lung cancer
Authors: D. Xiang, N. C. Garbett, J. Chaires, D. L. Laber, G. H. Kloecker
Journal: Journal of Clinical Oncology (2009)

e22074 Background: Currently, there are no clinically useful biomarkers for lung cancer (LC). We developed a novel approach by using differential scanning calorimetry (DSC) to analyze the plasma proteome of LC patients. Our assay produces a signature snapshot of the plasma proteome based on the thermal properties of the constituent proteins within the mixture. Each individual protein has a unique and characteristic melting temperature and melting enthalpy. These biophysical properties are as intrinsic and unique for each protein as are its sequence, mass, and charge. The denaturation of plasma results in a composite signature thermogram that represents the sum of all of the individual proteins within the proteome, weighted according to their concentration within the plasma or serum. Our goal is to identify unique thermogram profiles as biomarkers for lung cancer evaluation. Methods: Plasma samples were collected from LC patients and healthy volunteers. Sample analysis was performed using an automated capillary DSC. Comparison of plasma thermograms from controls and diseased individuals was done using quantile-quantile plots and the Kolmogorov-Smirnov test. Results: One hundred samples were obtained from healthy volunteers. DSC thermograms from control plasma were highly reproducible and yielded a characteristic signature with a well-defined shape and temperature maxima. Twenty samples from LC patients were obtained at diagnosis. Plasma from LC individuals yielded a unique thermogram that differs from that of healthy controls. Preliminary results suggested that DSC was sensitive to properties of the plasma proteins other than their charge and mass. We hypothesize that changes in thermogram shapes and positions in LC can arise from changes in the concentrations of plasma proteins, from disease-induced protein-protein interactions, or from the secretion into plasma of disease-related peptides that can bind to the most abundant plasma proteins. Conclusions: Lung cancer may have a characteristic signature thermogram that may serve as a biomarker for LC; further studies are needed to elucidate the biophysical and molecular mechanisms of different thermograms between normal individuals versus those with disease or cancer. No significant financial relationships to disclose.
Effects of morning blood pressure surge on cardiac arrhythmia and myocardial ischemia in patients with essential hypertension
Authors: Ping Li, Jian-chun Li
Journal: BMJ (2011)

Objective To investigate effects of morning blood pressure surge (MBPS) on cardiac remodeling and cardiovascular events in patients with essential hypertension.Methods Totally,386 patients with essential hypertension were recruited into the study,146 with MBPS and 240 without it based on their dynamic blood pressure monitoring.All the patients were monitored by 24-hour ambulatory blood pressure measurements,24-hour Holter electrocardiography and echocardiography for dynamic blood pressure,left ventricular mass index (LVMI),left atrial dimension (LAD),atrial and ventricular arrhythmias and ST depression,and so on.Results Compared with non-MBPS group,patients with MBPS had significantly higher incidence of left ventricular hypertrophy (LVH),enlargement of left atrial dimension,cardiac arrhythmias and myocardial ischemia detected,with LVMI [( 119 ±21 ) g/m2 vs.(93 ±12) g/m2,P＜0.01],LAD [(46±11) mmvs.(38±10) mm,P＜0.05],LVH (67.1% vs.30.4%,P ＜0.01 ),atrial premature beats (98.6% vs.84.2%,P ＜ 0.05 ),atrial tachycardia ( 54.1% vs.20.8%,P ＜ 0.01 ),atrial fibrillations ( 24.0% vs.0,P ＜ 0.0l ); ventricular premature beats and ventricular tachycardia ( 79.5% vs.57.9%,P ＜ 0.05,and 6.8% vs.2.5%,P ＜ 0.05 ),ST-segment depression (33.6% vs.13.8%,P ＜ 0.01 ),respectively.And,53.2 percent of cardiac arrhythmia and 57.6 percent of ST-segment depression occurred at six to eight o'clock in the morning.Blood pressure early in the morning and MBPS associated with ST-segment depression at the corresponding time ( P ＜ 0.05 ).Conclusions LVH is more significant,cardiac arrhythmias is severer and myocardial ischemia is more common in hypertensive patients with MBPS than that in those of non-MBPS.

Key words: 
Hypertension; Blood pressure; Arrhythmia; Myocardial ischemia
Clinical characteristics of variant angina patients with or without fixed coronary stenosis
Authors: Hong-bo Yang, Zhe-yong Huang, lei Xu, Ju-ying Qian, Jun-bo Ge
Journal: BMJ (2012)

Seventy-one patients with variant angina (VA) admitted in the Cardiology Department from January 2003 to March 2011,were divided into non-stenosis group (stenosis ＜ 50％,n =43) and stenosis group (stenosis ≥50％,n =28) according to the degree of stenosis.The differences of the risk factors,clinical manifestations,electrocardiogram,echocardiogram and laboratory examinations between these two groups were compared.The average age of patients in stenosis group 58 ± 8 y was higher than that in non-stenosis group (52 ± 9 y,t =2.43,P =0.02).Other risk factors,including male gender,smoking,hypertension,diabetes mellitus and lipid disorder did not show any differences between the two groups.Percentage of patients with angina pectoris lasting less than 5 min was higher in stenosis group (x2 =5.98,P =0.02),while percentage of effort angina,seeking medical consultation ≤ 6 months of onset and hemodynamic disorders showed no difference.Laboratory examinations had no differences.It is difficult to determine whether the VA patient has fixed coronary stenosis by analyzing the risk factors,clinical manifestations and laboratory examinations; to determine the fixed coronary stenosis coronary angiography is necessary.

Key words: 
Angina pectoris, variant; Coronary stenosis; Retrospective studies
Nuclide renal dynamic imaging for evaluating renal function in hydronephrotic kidneys with no image on intravenous urography and its significance
Authors: Yi Yao, Da-qing Tan, Qiang Li, Sheng-qi Lu
Journal: BMJ (2009)

Objective To explore clinical value of dynamic renal imaging in evaluating renal function of obstructively hydronephrotic kidney with no image on intravenous urography (IVU) by technetium-99m diethylenetriaminepentaacetic acid (99Tcm-DTPA). Methods A total of 48 patients with unilateral chronic severely obstructive hydronephrosis with no image on IVU and with normal renal function in the other side were enrolled in this study. All of them were undergone 99Tcm-DTPA dynamic renal imaging to evaluate the function of the sick kidney before and one to two weeks after percutaneous renal puncture (nephrostomy) and 24-hour drainage. And, data were compared with chi-square test. Results Before nephrostomy, only 13 of 48 (27%) hydronephrotic kidneys had function, with an average glomerular filtration rate (GFR) of (47±6) ml/min. Thirty-five of 48 (73%) hydronephrotic kidneys had no function, with an average GFR of (17±5) ml/min. But, after nephrostomy, 19 of them (40%) had function, with an average GFR of (56±5) ml/min, and 29 had no function with an average GFR of (17±5) ml/min. Function of the 19 functioning kidneys obviously recovered to varied extent six to 12 months after treatment with conservative operation. Conclusions 99Tcm-DTPA dynamic renal imaging should be used to evaluate the function of severely obstructive hydronephrotic kidneys with no image on IVU, which can reflect its objective function, especially one to two weeks after nephrostomy in hypertonic hydronephrostic kidneys, and is better than IVU.

Key words: 
Kidney function test;  Radionuclide imaging;  Urography;  Glomerular filtration rate;  Hydronephrosis
Tumor mutational load, microsatellite instability and actionable mutations in metastatic colorectal cancer: Results from the TRIBE2 study.
Authors: Carlotta Antoniotti, Federica Marmorino, Sara Lonardi, Francesca Corti, Daniele Rossini, Roberto Moretto, Clara Ugolini, Mirella Giordano, Emiliano Tamburini, Daniele Santini, Giuseppe Aprile, Roberto Bordonaro, Gemma Zucchelli, Gabriella Fontanini, Heinz-Josef Lenz, Alfredo Falcone, Wolfgang Michael Korn, Chiara Cremolini
Journal: Journal of Clinical Oncology (2020)

4077 Background: In the TRIBE2 study molecularly unselected and untreated mCRC patients were randomized to receive FOLFOXIRI/bevacizumab (bev) followed by the same agents after disease progression (PD) or FOLFOX/bev followed by FOLFIRI/bev after PD. We performed a comprehensive NGS analysis of samples from randomized patients in order to investigate the prognostic impact of tumor mutational load (TML), its additional value with respect to the assessment of microsatellite instability (MSI), and the overall prevalence of potentially actionable alterations. Methods: Tumor DNA was obtained from formalin-fixed, paraffin-embedded blocks from primary tumors of 296 (44%) out of 679 randomized patients and underwent NGS analysis using the Caris MI TumorSeek panel, assessing 592 genes. TML was defined low, intermediate or high if &lt; 7, 7-16 or &gt; 16 mutations/Mb were found. MSI status was determined both by NGS and by IHC. Results: TML and MSI were successfully determined by NGS in 224 (76%) cases. NGS and IHC results were concordant in 221 (99%) cases. TML was low, intermediate or high in 56 (25%), 157 (70%) and 11 (5%) cases, respectively. When compared with TML low and intermediate tumors, TML high were more frequently right-sided (p = 0.013), mucinous (p &lt; 0.001) and MSI-high (p &lt; 0.001). TML high tumors were MSI-high or MSS in 8 (73%) and 3 (27%) cases, respectively. Two out of 3 TML high and MSS tumours showed a pathogenic POLE mutation (p.S459F and p.P286R). The other TML high, MSS and POLE wt tumor was dMMR at IHC (loss of MSH6 expression) and showed a pathogenic MSH6 mutation (p.F1040fs). As compared with low and intermediate TML, high TML was associated with longer PFS (median PFS: 17.3 vs 10.6; HR: 0.54 [95%CI: 0.35-1.09], p = 0.098) and OS (median OS: not reached vs 23.7: HR: 0.45 [95%CI:0-28-1.13], p = 0.106). No interaction effect between TML and treatment arm was observed, and no difference between TML low and intermediate tumors was reported in terms of baseline characteristics and prognosis. Actionable alterations ( HER2 mutations [N = 2] and amplifications [N = 4], KRAS G12C [N = 10] and BRAF V600E mutation [N = 39]) were found in 55 (19%) out of 296 cases. No NTRK/ROS/ALK or MET amplification was found. Conclusions: TML high tumors are not limited to MSI-high ones but showed POLE or MSH6 somatic mutation and shower longer PFS and OS. No differences are reported between TML low and intermediate tumors. Molecular alterations predictive of benefit from targeted strategies currently available are detectable only in a small percentage of mCRCs.
Progress in gastric cancer screening with serum markers, endoscopy and imaging
Authors: Shouzhen Li, Xiaoli Wu, Yi Dong
Journal: BMJ (2019)

The morbidity and mortality of gastric cancer are high in China. It is of great significance to explore a screening scheme for gastric cancer that suits Chinese conditions. This article reviews the risk factors, the status of screening at home and abroad and the commonly used screening methods of gastric cancer. The articlealso recommends a screening model, in which endoscopic and imaging examination are applied for high-risk population identified by detection of the serum markers such as pepsinogen,gastrin-17 and Helicobacter pylori antibody.


Key words: 
Gastric neoplasm; Early detection of cancer; Gastroscopy; Ultrasonography; Serologic tests
Clinical characteristics, risk factors and prognosis of systemic lupus erythematosus complicated with digital gangrene: a study of 2684 cases
Authors: Xuan Zhang, Feng-chun Zhang
Journal: BMJ (2008)

Objective To study clinical manifestations, risk factors and prognosis of patients with systemic lupus erythematosus (SLE) complicated with digital gangrene. Methods Data of 2684 inpatients with SLE admired to Peking Union Medical College Hospital during December 1997 to August 2007, including demographic information, clinical features, laboratory findings, as well as therapeutic regimens, were retrospectively analyzed, and 18 of those complicated with digital gangrene were identified and followed up. Results Average age at onset in patients of SLE complicated with digital gangrene was(33±12)years, with an average duration of disease course of (99±60 ) months. Longer course duration ( ≥ 4 yrs), Raynaud's phenomenon, elevated serum C-reactive protein (CRP) and positive anti-SSA antibody all were associated with occurrence of digital gangrene in patients of SLE, with P values of 0.012, 0.004, 0.037 and 0.087 respectively, and odds ratios of 1.03 (95% CI 1.01～1.05 ), 39.05 (95% CI 3.31～460.13 ), 17.99 (95%(CI 1.19～271.29) and 7.01 (95% CI 0.75～65.12), respectively. Fifteen of 18 SLE patients complicated with digital gangrene started treatment with predisone ≥1 mg˙kg-1 ˙d-1, and eighteen all were treated with cyclophosphamide, though eight cases failed and ultimately received digital amputation. Prompt corticosteroid treatment (predisone ≥ 1 mg˙kg-1˙d-1 within three weeks after occurrence) could decrease risk for amputation, with P =0.081 and OR =0.135 (95% CI 0.01～1.28). Conclusions Longer duration of disease course, Raynaud's phenomenon, elevated serum CRP and positive anti-SSA antibody all are independent predictors of SLE complicated with digital gangrene. Early and aggressive treatment can prevent occurrence of gangrene from its progression and improve its prognosis.

Key words: 
Lupus erythematosus,systemic;  Fournier;  Raynand disease;  C-reactive protein
A precision medicine drug discovery pipeline to identify dual CDK2/9 inhibition as a novel treatment for colorectal cancer.
Authors: Roham Salman Roghani, Ali Sanjari moghaddam, Gabrielle Rupprecht, Erdem Altunel, So Young Kim, Shannon McCall, Beatrice Thomas, Katie Ware, Jason Somarelli, David S. Hsu
Journal: Journal of Clinical Oncology (2020)

e16056 Background: Colorectal cancer (CRC) is the 3 rd most common form of cancer in the US, responsible for over 50,000 death each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new therapies to treat this deadly disease. To address this need, we have developed a precision medicine pipeline that integrates high throughput chemical screens with matched patient-derived cell lines and patient-derived xenografts (PDXs) to identify new treatments for CRC. Methods: We used high-throughput chemical screens of 2,100 compounds across five low-passage, patient-derived CRC cell lines. These results were validated using dose-response IC 50 curves for CDK1, CDK2, CDK9 or CDK1/2/9 inhibitors and by siRNA-mediated knockdown of CDK9 with or without CDK2 inhibition. Cell cycle arrest analysis was performed by flow cytometry and anaphase catastrophe was analyzed by immunofluorescence staining. For in vivo studies, matched PDXs were treated with either CDK2, CDK9 or dual CDK2/9 inhibitors. Results: We identified the CDK inhibitor drug class as among the most effective cytotoxic compounds across all five CRC lines. Further analysis of the CDK inhibitor class revealed that combined targeting of CDK1, 2, and 9 was the most effective, with IC50 in the range of 110 nM to 1.2 μM. We further validated the efficacy of combined CDK2/9 inhibition using siRNA-mediated knockdown of CDK9 in the presence of a CDK2 inhibitor(CVT-313), and showed that CDK9 knockdown acted synergistically with CDK2 inhibition. Dual CDK2/9 inhibition led to significant G2/M cell cycle arrest and anaphase catastrophe. Finally, combined CDK2/9 inhibition in vivo synergistically inhibited PDX tumor growth as compared to single-agent CDK inhibitors. Conclusions: Our precision medicine pipeline revealed CDK2/9 dual inhibition as a combinatorial therapy to treat CRC and can also be used to identify new and novel therapies