tbuckley/cabot-search huggingface dataset:
Lifestyle and the presence of helminths is associated with gut microbiome composition in Cameroonians
Authors: Meagan A. Rubel, Arwa Abbas, Louis J. Taylor, Andrew Connell, Ceylan Tanes, Kyle Bittinger, Valantine N. Ndze, Julius Y. Fonsah, Eric Ngwang, André Essiane, Charles Fokunang, Alfred K. Njamnshi, Frederic D. Bushman, Sarah A. Tishkoff
Journal: Genome biology (2020)

Abstract Background African populations provide a unique opportunity to interrogate host-microbe co-evolution and its impact on adaptive phenotypes due to their genomic, phenotypic, and cultural diversity. We integrate gut microbiome 16S rRNA amplicon and shotgun metagenomic sequence data with quantification of pathogen burden and measures of immune parameters for 575 ethnically diverse Africans from Cameroon. Subjects followed pastoralist, agropastoralist, and hunter-gatherer lifestyles and were compared to an urban US population from Philadelphia. Results We observe significant differences in gut microbiome composition across populations that correlate with subsistence strategy and country. After these, the variable most strongly associated with gut microbiome structure in Cameroonians is the presence of gut parasites. Hunter-gatherers have high frequencies of parasites relative to agropastoralists and pastoralists. Ascaris lumbricoides , Necator americanus , Trichuris trichiura , and Strongyloides stercoralis soil-transmitted helminths (“ANTS” parasites) significantly co-occur, and increased frequency of gut parasites correlates with increased gut microbial diversity. Gut microbiome composition predicts ANTS positivity with 80% accuracy. Colonization with ANTS, in turn, is associated with elevated levels of TH1, TH2, and proinflammatory cytokines, indicating an association with multiple immune mechanisms. The unprecedented size of this dataset allowed interrogation of additional questions—for example, we find that Fulani pastoralists, who consume high levels of milk, possess an enrichment of gut bacteria that catabolize galactose, an end product of lactose metabolism, and of bacteria that metabolize lipids. Conclusions These data document associations of bacterial microbiota and eukaryotic parasites with each other and with host immune responses; each of these is further correlated with subsistence practices.
A 12-week clevudine therapy showed durable antiviral activity and normalization of alanine transminase levels for 6 months after discontinuation of treatment in patients with chronic hepatitis B.
Authors: HS Lee, YH Chung, KS Lee, KS Byun, SW Paik, Jy Han, K Yoo, SG Hwang, BC Yoo, JH Lee
Journal: Hepatology (2018)
The assessment accuracy of GP preceptors in mini-CEX workshops
Authors: Hua Yang, Qian Chen, Zhigang Pan, Shanzhu Zhu
Journal: BMJ (2014)

Objective
To evaluate the validity of GP proceptors in mini-CEX workshop.


Methods
Three mini-cex workshops for GP proceptors of standardized training of general practitioners in Shanghai were held during November 2009 to September 2012. In the workshops 82 GP proceptors gave the complete rating scores for the training videotapes and the assessment accuracy was analyzed.


Results
The accurate rates of all items including history taking, physical examination, communication, clinical judgement, consulting skills, organisation and overall clinical perfomance were lower than 50% in 9-point scale and the completely accurate rate and completely error rate were 1.2% and 30.5%, respectively. The accurate rates of 5 items were more than 50% in 3-rank system and the completely accurate rate and completely error rate were 3.7% and 9.8%, respectively. The accurate rates of 4 items were more than 50% in standard score±1 system and the completely accurate rate and completely error rate were 8.5% and 2.4%, respectively. Comparing with 9-point scale, 3-rank system had higher accurate rate in 5 items(P<0.05)and standard score±1 system had higher accurate rate in all 7 items(P<0.05). Abnomal rating scores were found more common in medical interview (41, 50.0%), clinical judgement (32, 39.0%) and physical examination (13, 20.7%). GP proceptors with more than five years teaching experience were more likely to give error scores than those with five or less years teaching experience in 9-point scale(OR=6.993) and 3-rank system(OR=4.902). Leniency and halo effects occurred in 11(13.4%) and 8(9.8%) GP proceptors, respectively; and 14 (17.1%) GP proceptors gave written feedback.


Conclusions
The rater accuracy of GP proceptors in mini-CEX workshop should be improved further.


Key words: 
General practioner; Teach; Mini clinical evaluation exercise
The value of tumor markers in monitoring of non-small cell lung cancer
Authors: Lin Cui
Journal: BMJ (2009)

One hundred and four patients with non-small cell lung cancer (NSCLC) and 17 patients with benign lung lesions were enrolled in the study. Carcinoembryonic antigen ( CEA), neural specific enolaee (NSE) and cytokemtin 19 fragment (CYFRA21-1) in serum were detected by dectruchemiluminescence method before and after operation. The serum levels of three markers in preoperative NSCLC patients were significandy higher than those of benign pulmonary diseases group (t = 7. 930, 5.568, 6. 110, P   0.05 ). There were significant differences in serum levels of CEA, NSE and CYFRA21-1 before and after operation in NSCLC group ( t = 5.419, 4.722, 5.779, P  0.05). This study indicates that detection of serum CEA, NSE and CYFRA21-1 is of monitoring value for treatment of non-small cell lung cancer.

Key words: 
Cancinoma, non-small cell lung;  Tumor markers,biological
Artificial intelligence assisted bone lesion detection and classification in computed tomography scans of prostate cancer patients.
Authors: Samira Masoudi, Sherif Mehralivand, Stephanie Harmon, Stephanie Walker, Peter A. Pinto, Bradford J. Wood, Deborah E. Citrin, Fatima Karzai, James L. Gulley, Ravi Amrit Madan, William L. Dahut, Peter L. Choyke, Baris Turkbey
Journal: Journal of Clinical Oncology (2020)

e17567 Background: Patients diagnosed with prostate cancer undergo computed tomography (CT) for pretreatment staging to rule out bone metastases. However, detection and classification of bone lesions on CT is challenging and subject to inter-reader variability. We present a cascaded deep learning algorithm for automatic detection and classification of bone lesions on staging CT in patients diagnosed with prostate cancer. Methods: CT scans from 56 patients with histopathologically proven prostate cancer were included. An expert radiologist annotated the extent of individual bone lesions (N = 4217) and labelled all regions as either benign or malignant. All scans were anonymized and normalized at the patient-level prior to training. Our method can be described as a two-stage framework, 1) A detection algorithm: Inspired by Yolo-v3 detection method, we designed a network with a backbone of darknet-53 pretrained on Coco dataset and four final scaling blocks to compensate for wide range of lesion diameters, 2) A classification algorithm: we formed a binary classifier based on ResNet-50 pretrained using the ImageNet dataset. We used a train/validation split equal to 90%/10% for this study. To facilitate the learning process, horizontal flipping, relative zooming and mean weighted averaging were used for data augmentation in stage 1. Instead, the classification algorithm took advantage of synthesized patches generated by Deep Convolutional Generative Adversarial Network (DC-GAN) for augmentation. Results: We could achieve a real-time (~120ms per slice) performance on our validation set with a median penalty of 0.3(0.02-0.78) false positives per true positive within each patient. Overall performance of our detection algorithm was 81% sensitivity and 86% positive predictive value. In stage 2, we obtained an accuracy of 89% for correct classification of benign from malignant bone lesions with no augmentation which was improved to 91% when we incorporated the augmented data for training. Conclusions: Our 2-stage algorithm sequentially detects and classifies bone lesions on CT of prostate cancer patients with a significant performance. To further improve our results and for generalizability we are accruing more data from different centers. Eventually, with greater dataset, both algorithms will be cascaded and trained as a whole unit to become one single tool for fully automatic detection and classification which serves as an aid for radiologists who read the staging CTs.
Baseline biomarkers correlated with outcome in advanced melanoma treated with pembrolizumab monotherapy.
Authors: Gil Awada, Julia Katharina Schwarze, Odrade Gondry, Yanina Jansen, SuFey Ong, Kara M. Gorman, Sarah Warren, Mark Kockx, Teofila Seremet, Marleen Keyaerts, Hendrik Everaert, Bart Neyns
Journal: Journal of Clinical Oncology (2020)

e22041 Background: Pembrolizumab (PEMBRO) improves survival in advanced melanoma (MEL). This research investigates baseline (BL) biomarkers that predict long-term benefit on PEMBRO monotherapy. Methods: Outcome data on patients (pts) with advanced cutaneous/mucosal MEL treated with PEMBRO in our institution were collected after pt consent. Responses were evaluated using the immune-related response criteria. Total metabolic tumor volume (TMTV), assessed by 18-fluorodeoxyglucose positron emission tomography/computed tomography, was calculated as the sum of all tumor-associated voxels with a standardized uptake value (SUV) above the mean SUV measured in a reference region in normal liver tissue plus 3 standard deviations using Syngo.via software (Siemens Healthcare). The NanoString PanCancer IO360 panel was used for gene expression profiling (GEP). Results: A total of 196 pts was included in this analysis (median age 60; cutaneous 86%, mucosal 3%, unknown primary 12%; stage III 14%, IV-M1a/b/c 60%, IV-M1d 26%; first-line 24%). Median progression-free survival (PFS) in the population was 20.4 w (95% CI 10.2-30.7); median overall survival (OS) was 143.6 w (95% CI NR-NR). BL WHO Performance Status (PS) &gt; 0 (HR 1.63 [95% CI 1.13-2.37]), C-reactive protein (CRP) &gt; ULN (HR 1.92 [95% CI 1.33-2.77]), absolute lymphocyte count (ALC) &lt; 750/mm³ (HR 2.45 [95% CI 1.32-4.55]) and &gt; 1 metastatic site (HR 1.84 [95% CI 1.23-2.77]) were associated (P≤0.01) with worse PFS in multivariate analysis (Cox regression); BL WHO PS &gt; 0 (HR 2.77 [95% CI 1.82-4.24]), lactate dehydrogenase (LDH) &gt; ULN (HR 1.80 [95% CI 1.16-2.79]) and &gt; 1 metastatic site (HR 1.95 [95% CI 1.16-3.25]) were associated with worse OS (P≤0.011). BL TMTV data were available in 118 pts (60%): BL CRP &gt; ULN (HR 1.83 [95% CI 1.13-2.96]), ALC &lt; 750/mm³ (HR 2.49 [95% CI 1.02-6.08]), &gt; 1 metastatic site (HR 1.71 [95% CI 1.04-2.82]) and BL corticosteroid use (HR 4.62 [95% CI 1.38-15.45]) were associated with worse PFS (P &lt; 0.05). BL WHO PS &gt; 0 (HR 2.82 [95% CI 1.57-5.08]), ALC &lt; 750/mm³ (HR 2.62 [95% CI 1.06-6.51]), history of brain metastases (HR 2.59 [95% CI 1.37-4.91]) and TMTV &gt; 80 mL (HR 3.56 [95% CI 1.82-6.95]) were all associated with worse OS (P≤0.038). GEP data on a representative BL tumor sample were available in 27 pts (14%). Higher apoptosis signature scores were associated with increased probability of OS (HR 0.45 [95% CI 0.33-0.73], P &lt; 0.01). Conclusions: BL TMTV &gt; 80 mL identifies a subgroup of advanced MEL pts with worse outcome on PEMBRO. Increased apoptosis gene signature scores in a subset of patients predict increased OS.
慢性阻塞性肺疾病患者生存质量评估
Authors: 蔡映云, 李倬哲, 方宗君
Journal: BMJ (2004)

生命包括生命活动的持续时间(寿命)和生命活动水平的高低(质量)两方面内容.以往医疗卫生工作者主要关注如何延长患者的寿命和改善生物学指标,随着生物-心理-社会医学模式的提出,以及人民经济条件生活水平的提高, 生存质量 (quality of life,QOL)这一概念引起重视.尽管目前还缺乏一个生存质量的统一定义,一般认为生存质量指个体对其生活领域里的表现情况的满意度和幸福感.生存质量不仅反映了生理功能,还涉及到心理状态和社会交往.生存质量用以评估个人或群体的躯体功能、心理情绪和社会适应的综合水平,包括躯体健康(如症状、活动能力及健康自我评价)、社会适应(如社会交往情况、参与社会活动的程度和学习能力)以及心理情绪(焦虑、抑郁、认知、幸福感、满意度等)。
Diagnosis and treatment of senile brucellosis spondylitis
Authors: Xinming Yang, Wei Shi, Xianyong Meng, Changbo Hu, Peng Zhang, Yaoyi Wang, Yongli Jia, Zhenshun Hu
Journal: BMJ (2014)

A total of 38 cases of senile brucella spondylitis disease at our hospital during January 2002 and March 2012 were analyzed. After admission, all of them were definitely diagnosed on the basis of epidemiological history, clinical manifestations, laboratory tests, imaging and pathological examinations. Over a follow-up period of 12 months, 17 cases were cured after standardized drug treatment. Among 21 surgical cases, there were curing (n=17) and improving (n=2). Senile brucellosis spondylitis has distinct serological and pathological characteristics. And formulating the diagnostic criteria may improve its diagnostic rate and reduce its misdiagnostic rate. And standardized drug therapy achieves a better curing rate and a proper timing of surgical intervention improves its clinical outcomes.


Key words: 
Brucellosis; Myelitis
SKB264 ADC: A first-in-human study of SKB264 in patients with locally advanced unresectable/metastatic solid tumors who are refractory to available standard therapies.
Authors: Yongheng Liu, Wei Lian, Xi Zhao, Yina Diao, Jian Xu, Liang Xiao, Yan Qing, Tongtong Xue, Jingyi Wang
Journal: Journal of Clinical Oncology (2020)

TPS3659 Background: Elevated expression of trophoblast antigen 2 (TROP2) is often associated with invasion/aggression, progression, and metastasis of many different tumor types. Efficacies of anti-TROP2 ADC have been demonstrated both pre-clinically and in the clinical trials. SKB264 is being developed as a further optimized TROP2-targeting ADC with a proprietary cytotoxic, belotecan-derived payload and novel stable conjugation chemistry to achieve average DAR (Drug Antibody Ratio) of 7.4. Release of payload upon SKB264 internalization is in a TROP2 expression dependent manner. Extensive preclinical studies demonstrated antitumor activity of SKB264 in vitro, in xenograft and patient-derived xenograft (PDX) animal models. In addition, safety studies have demonstrated a good safety profile to allow SKB264 to be studied in clinical trials. Methods: SKB264-01 is a global open label multicenter study. The study is divided into 2 parts, the phase I is to determine the safety profile, define MTD and/or the RP2D, and characterize DLTs of SKB264. Dose escalation and MTD identification will be directed using a Bayesian logistic regression model (BLRM) with overdose control. The phase II is to evaluate efficacy and obtain clinical activity data of SKB264 as a monotherapeutic agent at the RP2D in each of the designated Phase II cohorts and overall (n = 16 per cohort; n = 48 for entire Phase II part). Objective response rate (ORR) will be continuously evaluated in each cohort using a Bayesian hierarchical model. TROP2 assessments will not be performed prior to enrollment but it will be assessed retrospectively. Confirmation of TROP2 expression by immunohistology or other methods is not required, but the Sponsor will request tissue specimens from archived materials for determination of TROP2 expression. The patient must have, in the judgment of the investigator, historically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types: i. ovarian epithelial cancer, ii. gastric adenocarcinoma, iii. pancreatic adenocarcinoma, iv. triple negative breast cancer, v. bladder cancer. Patient will receive study drug as a single IV infusion at the prescribed dose level at each administration. Cycles will continue until disease progression or unacceptable toxicity. Adverse Events (AE) will be graded according to CTCAE V.5.0. Responses will be evaluated according to RECIST V1.1. The enrollment will began in Mar 2020 in USA sites. Clinical trial information: NCT04152499 .
被误诊的梗阻性黄疸患者
Authors: 曾昭耆
Journal: BMJ (2004)

患者男,60岁,因发现黄疸3个月,伴恶心、呕吐、食欲减退到北京求治.曾先后在4家有名的医院门诊做过多种检查.实验室检查发现胆红素明显增高,以直接胆红素为主,伴有丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶及碱性磷酸酶等增高.影像学检查(肝扫描、B超等)示胰头肿大,结构紊乱,故各医院均诊断为胰头癌。
Satisfaction level and stability of medical staff's work in pre-hospital care in Qingdao
Authors: Mei Xu, Run An, Ming-xia Wang, Xue-qi Sheng
Journal: BMJ (2012)

A total of 256 medical professionals at the hospitals of different levels were interviewed and requested to complete the relevant questionnaires.The findings revealed that the top five unsatisfied items were growth & development,working conditions,doctor-patient relationship,income and social status.The levels of job satisfaction varied with their specific occupations and technical titles.Around two thirds of them once had the thought of leaving their pre-hospital care posts.

Key words: 
Attitude of health personnel;  Questionuaires
Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer
Authors: Avinash Kumar, Ekta Rathi, Raghu Chandrashekar Hariharapura, Suvarna G. Kini
Journal: Medicinal Research Reviews (2020)

Abstract An understanding of the pathology of cervical cancer (CC) mediated by E6/E7 oncoproteins of high‐risk human papillomavirus (HPV) was developed by late 80's. But if we look at the present scenario, not a single drug could be developed to inhibit these oncoproteins and in turn, be used specifically for the treatment of CC. The readers are advised not to presume the “viability of E6 protein” as mentioned in the title relates to just druggability of E6. The viability aspect will cover almost everything a researcher should know to develop E6 inhibitors until the preclinical stage. Herein, we have analysed the achievements and shortcomings of the scientific community in the last four decades in targeting HPV E6 against CC. Role of all HPV proteins has been briefly described for better perspective with a little detailed discussion of the role of E6. We have reviewed the articles from 1985 onward, reporting in vitro inhibition of E6. Recently, many computational studies have reported potent E6 inhibitors and these have also been reviewed. Subsequently, a critical analysis has been reported to cover the in vitro assay protocols and in vivo models to develop E6 inhibitors. A paragraph has been devoted to the role of public policy to fight CC employing vaccines and whether the vaccine against HPV has quenched the zeal to develop drugs against it. The review concludes with the challenges and the way forward.
惊厥误诊为癫痫6年
Authors: 吴明昌
Journal: BMJ (2010)

一个12岁男童患癫痫6年,因近2个月来体检发现室性早搏由外地来京就诊.患儿自6岁起发生惊厥,发作时全身肌阵挛发作,短暂失神,跌倒在地,瞬间止抽,1～2分钟后神智清醒,玩耍自如.当地查脑电图正常,诊断癫痫,予苯妥因钠治疗,定期体检.间断服药时每年发作1～2次,若停药则每2～3个月发作1次,甚至每天也有1～2次发作,多在劳累或看电视紧张时发作.头颅CT正常.上学智能正常.无癫痫家族史。
Targetable immune checkpoint molecules may be significantly differentially expressed in minority ethnicities.
Authors: Jacob J. Adashek, Christopher Szeto, J. Zack Sanborn, Sandeep K. Reddy, Amir A. Toor, Stamatina Danielides, Steven Smith, Steven R. Grossman, Charles V Clevenger, Anthony Faber, Andrea Ferreira-Gonzalez, Sosipatros Alexandros Boikos
Journal: Journal of Clinical Oncology (2020)

3576 Background: Studies of immune checkpoint blockade therapy (ICT) outcomes have been largely performed in melanoma and lung cancer patients, both of which are enriched for White patients. For example, a National Cancer Database study found that 97% of first-line ICT treatments in melanoma have been administered to White recipients (Patel, ASCO-SITC 2020). Given expanding indication in tumor types affecting more diverse populations, we sought to study whether minority populations might be projected to have differing checkpoint blockade response rates. Methods: Ethnicity information and RNAseq expression profiles and primary site information were obtained for 7087 patients from TCGA. Ethnicity was tested for association with RNA expression of targetable checkpoint genes ( PD1, PDL1, PDL2, CTLA4, IDO1, LAG3, TIM3, TIGIT, OX40, VISTA, and GITR) in 5 tumor histology types by Wilcoxon methods with Benjamini-Hochberg correction for multiple hypothesis testing. A dataset of &gt; 2700 cases was obtained from NantHealth, with paired whole exome/RNAseq data. Ethnicity for 579 patients was assigned using allele-fraction from ~250 single nucleotide polymorphic sites found exclusively in 6 populations within the 1000 Genomes project. Ethnicity/checkpoint associations found in TCGA were tested within this dataset. Results: Within the TCGA cohort, ethnicity was not a factor in differential expression of checkpoint molecules in lung cancer. Within melanomas, in Asian patients PDL1, CTLA4, and IDO1 were expressed at lower levels than in White patients (each p = 0.04). These associations did not remain significant after correction for multiple hypothesis testing. Breast cancers in Black patients had significantly higher PD1, CTLA4, IDO1, LAG3, GITR, and OX40 expression compared to White patients, all remaining significant after correction (adj. p 3.7e-5 to 6.4e-3). Among White patients, colon cancers showed higher expression of PDL1/2, IDO1, LAG3, TIM3, and GITR (p 0.04 to 0.0017). IDO1 was significantly higher in White patients even after correction (adj. p = 0.03), and lower in Black patients (adj. p = 0.03). Conclusions: Ethnicity may represent a significant factor for efficacy checkpoint blockade therapies. White breast cancer patients might be anticipated to exhibit reduced sensitivity to PD1/CTLA4 blockade, while Black colon cancer patients may exhibit reduced sensitivity to IDO1 therapies such as epacadostat. A biomarker-driven approach to patient selection may ameliorate ethnic disparities in ICT outcomes.
Clinical and renal pathological findings in children infective endocarditis
Authors: Chaoying Chen, Jingcheng Liu, Li Cao, Lina Ji, Li Wang, Lin Shi
Journal: BMJ (2015)

We retrospectively analyzed the clinical manifestations, treatments and prognosis of infective endocarditis (IE)associated with renal lesions in children. There were 23 confirmed IE cases who were admitted to the Capital Institutes of Pediatrics from 1992 to 2012. There were 6 cases (26%) with renal lesions. Renal lesions included asymptomatic microscopic hematuria(1 case), asymptomatic proteinuria(1 case) and acute nephritic syndrome (4 cases). There were 3 cases of acute renal injury (AKI) resulted from nephritis accompanied with acute heart failure. The serum level of C3 was lower in patients with renal lesions than patients without renal lesions (P 0.05). Renal lesions secondary to IE are relatively common in IE patients in children. Most of renal lesions can be improved by effective antibiotics. Prognosis of those patients accompanying with AKI is bad.


Key words: 
Endocarditis; Kidney disease