tbuckley/cabot-search huggingface dataset:
Estimating Epidemic Incidence and Prevalence from Genomic Data
Authors: Timothy G Vaughan, Gabriel E Leventhal, David A Rasmussen, Alexei J Drummond, David Welch, Tanja Stadler
Journal: Molecular Biology and Evolution (2019)

Abstract Modern phylodynamic methods interpret an inferred phylogenetic tree as a partial transmission chain providing information about the dynamic process of transmission and removal (where removal may be due to recovery, death, or behavior change). Birth–death and coalescent processes have been introduced to model the stochastic dynamics of epidemic spread under common epidemiological models such as the SIS and SIR models and are successfully used to infer phylogenetic trees together with transmission (birth) and removal (death) rates. These methods either integrate analytically over past incidence and prevalence to infer rate parameters, and thus cannot explicitly infer past incidence or prevalence, or allow such inference only in the coalescent limit of large population size. Here, we introduce a particle filtering framework to explicitly infer prevalence and incidence trajectories along with phylogenies and epidemiological model parameters from genomic sequences and case count data in a manner consistent with the underlying birth–death model. After demonstrating the accuracy of this method on simulated data, we use it to assess the prevalence through time of the early 2014 Ebola outbreak in Sierra Leone.
Abstract P3-07-07: Withdrawn
Authors: Y-Z Jiang, D Ma, C Suo, J Shi, M Xue, DG Stover, C Verschraegen, V Kaklamani, P Wang, L Shi, W Huang, Z-M Shao
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Jiang Y-Z, Ma D, Suo C, Shi J, Xue M, Stover DG, Verschraegen C, Kaklamani V, Wang P, Shi L, Huang W, Shao Z-M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-07.
Combined over-the-scope clip and detachable snare placement for closure of an enterocutaneous fistula
Authors: Eduardo Rodrigues-Pinto, Rui Morais, Guilherme Macedo
Journal: Endoscopy (2019)

A 75-year-old man underwent a laparoscopic extended right hemicolectomy for malignant colorectal adenocarcinoma of the distal transverse colon. The postoperative course was complicated by pneumonia in the left lung and acute pancreatitis. The patient presented 30 days after surgery with increased abdominal pain and septic shock.
Abstract P5-12-12: ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer patients
Authors: B Győrffy, J Fekete
Journal: Cancer Research (2019)

Abstract Prognostic biomarkers are capable to predict survival and predictive biomarkers are capable to predict therapy response. Systemic therapy of breast cancer can include chemotherapy, hormonal therapy, and targeted therapy. Here, we report the initial release of the first online available tool capable to identify gene expression based predictive biomarkers using transcriptomic data of a large set of breast cancer patients. Published gene expression data of 44 publicly available datasets was integrated with treatment data into a unified database. The classification is based on either author-reported pathological complete response (n=1,775) or relapse-free survival status at five years (n=1,329). Treatment data includes chemotherapy (n=2,108), endocrine therapy (n=971), and anti-HER2 therapy (n=267). The transcriptomic database includes 20,089 unique genes and 54,675 probe sets. Gene expression and therapy response are compared using receiver operating characteristics and Mann-Whitney tests. We demonstrate the utility of the tool by validating a set of established biomarkers including TP53 for chemotherapy in luminal breast cancer (p=5.2e-20, AUC=0.77), ERBB2 for trastuzumab therapy (p=8.4e-04, AUC=0.629), and PGR for hormonal therapy (p=8.6e-05, AUC=0.7). The tool is designed to validate and rank new predictive biomarker candidates in real time. By analyzing the selected genes in a large set of independent patients, one can select the most robust candidate and quickly eliminate those which are most likely to fail in a clinical setting. The analysis tool is accessible at www.rocplot.org/breast. Citation Format: Győrffy B, Fekete J. ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-12.
Paid revision courses: time for a boycott
Authors: Grant S Nolan
Journal: BMJ (2014)

They message me more than my girlfriend does, I see their shiny leaflets plastered on the student union’s walls, and one plucky company representative even had the audacity to give a quick sales pitch after a lecture. Exam season is looming, and paid revision courses are everywhere.

Medical schools have been around for centuries, educating bright eyed students. They teach us everything from approaching an unconscious patient in the street, to explaining the stomach ache one gets after being kicked in the balls.* Medical societies often provide revision events and proactive students have long formed their own revision groups; testing each other and working together through indecipherable lecture notes. So what gap are these revision courses plugging?

That …
Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion
Authors: MinKe He, QiJiong Li, RuHai Zou, JingXian Shen, WanQiang Fang, GuoSheng Tan, YuanMin Zhou, XiaoPing Wu, Li Xu, Wei Wei, Yong Le, ZhongGuo Zhou, Ming Zhao, Ying Guo, RongPing Guo, MinShan Chen, Ming Shi
Journal: JAMA Oncology (2019)

Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study.To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion.This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months.Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks).The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment.For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]).Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion.ClinicalTrials.gov identifier: NCT02774187.
Abstract 2487: Torsional and Reverse Rotational Mechanics of the Left Ventricular Apex Is Abnormal in Patients with Type 2 Diabetes Mellitus Independent of Presence of Hypertension, Left Ventricular Hypertrophy, Elevated Filling Pressures and Left Atrial Volume
Authors: Wei Zhao, Peng Li, Geu-Ru Hong, Shizhen Liu, Helene Houle, Gianni Pedrizzetti, Goivanni Tonti, Jagat Narula, Mani A Vannan
Journal: Circulation (2007)

Background : Diastolic dysfunction (DD) is common in patients with Type 2 DM even in the absence of HTN and LVH. We tested whether apical rotational mechanics offered any additional insights into DD in DM over conventional echo-Doppler measures. Methods: We studied 4 groups : 12 normals (wall thickness-WT 0.9±0.1cm); 17 patients with DM (WT 1.0±0.1cm, HbA1c 7±1%, BP 128±4/68±5 mmHg); 16 patients with DM +HTN (WT 0.9±0.1cm, HbA1c 7±1%, BP 134±23/72±18 mmHg); and 20 patients with DM+HTN+LVH (WT 1.4±0.2cm, HbA1c 7±4%, BP 135±13/76±9mmHg). All patients had normal LVEF and mitral E/A ratio. SAX of the LV apex and base were obtained. Velocity Vector Imaging (Siemens, CA) was used to measure: Longitudinal myocardial velocity (LMV, cm/sec) and strain (LS,%); Apical rotation velocity (ARV, cm/sec)and reverse rotation velocity(ARRV, cm/sec); Apical rotation (AR, degree) and LV torsion-LVTOR (degree/cm, and Circumferential (CS,%) and Radial strains (RS,%). Results: Figure shows LVTOR and % reduction in ARRV data. All other data will be presented. Thus, LV torsion is increased in DM alone or DM+HTN (-LVH) groups. But ARRV is reduced by ~ 20% in these groups even with relatively normal E/E’ ratio and LAVI. In the DM+HTN+LVH group, E/E’ and LAVI are increased and apical rotational mechanics resemble the same spectrum as the above groups but are more severe (~25% reduction in ARRV). Thus, reduction in ARRV is a marker of early DD in DM even in the absence of LVH . Conclusions: Apical rotational mechanics is more sensitive than conventional echo-Doppler measures to identify myocardial DD in type 2 DM even in the presence of normal E/A ratio, LAVI and LVEF, and in the absence of HTN and/or LVH.
Abstract P4-10-04: Assessment of clinical trial participation on breast cancer survival
Authors: C Parise, V Caggiano
Journal: Cancer Research (2019)

Abstract Background Accredited cancer treatment centers offer clinical trials for patients since it is universally accepted that participation in these trials is advantageous. Purpose The purpose of this study was to assess whether clinical trial participation was associated with a survival advantage. Methods We identified 308,291 cases of first primary female invasive breast cancer from the California Cancer Registry 2000-2015. Participation in a clinical trial was documented. Clinical trials were defined as National Cancer Institute (NCI) sponsored studies such as National Surgical Adjuvant Breast and Bowel Project (NSABP) and Southwest Oncology Group (SWOG); pharmaceutical trials; and local investigator initiated studies. The distribution of age, race/ethnicity, socioeconomic status (SES), and stage between clinical trial participants and non-participants was compared using contingency tables and the χ2 Test. Kaplan-Meier Survival Analysis and the Log Rank test were used to compare differences in breast cancer specific survival between participants and non-participants. Cox Regression Analysis was used to estimate the risk of mortality between participants and non-participants after adjusting for age, race/ethnicity, SES, grade, and treatment. Analyses were conducted separately for each stage. Hazard ratios (HR) and 95% confidence intervals (CIs) were reported. Results There were 3,517 (1.1%) patients who participated in a clinical trial. Almost 50% of participants were enrolled in an NCI trial, 38% in a local/investigator initiated study, and 13% were in a trial sponsored by a pharmaceutical company. Trial participation was highest for patients less than 45 years of age (21.9%) and lowest in patients 70 years of age and older (12.3%). Most participants were in stage 2 (44.6%). Participation increased with increasing SES. Only 8.5% of participants were in the lowest SES whereas 35.4% were in the highest SES. Unadjusted survival analysis indicated that there was no survival advantage for stage 1 patients (χ2 = 0.41, p=0.52) whereas study participants in stages 2, 3, and 4 had statistically significantly better survival. Adjusted hazard ratios indicated that stage 2 patients participating in a trial had a 23% reduced risk of mortality (HR=0.77; CI: 0.65 - 0.94). For patients in stage 4, the risk of mortality was reduced by 36% (HR=0.64; CI: 0.47 - 0.87). There was no risk reduction for patients in stages 1 and 3. Conclusion Only a small percent of patients enroll in breast cancer clinical trials and participation is correlated with age and SES. There is a survival advantage for participation in a clinical trial for stages 2 and 4 patients. Citation Format: Parise C, Caggiano V. Assessment of clinical trial participation on breast cancer survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-04.
Abstract P3-07-09: Tumour clonality in paired invasive breast carcinomas
Authors: J Biermann, TZ Parris, S Nemes, A Danielsson, H Engqvist, E Werner Rönnerman, E Forssell-Aronsson, A Kovács, P Karlsson, K Helou
Journal: Cancer Research (2019)

Abstract Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours. Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours. Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features. Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting. Citation Format: Biermann J, Parris TZ, Nemes S, Danielsson A, Engqvist H, Werner Rönnerman E, Forssell-Aronsson E, Kovács A, Karlsson P, Helou K. Tumour clonality in paired invasive breast carcinomas [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-07-09.
Novel C-17 spirost protostane-type triterpenoids from Alisma plantago-aquatica with anti-inflammatory activity in Caco-2 cells
Authors: Qinghao Jin, Jianqing Zhang, Jinjun Hou, Min Lei, Chen Liu, Xia Wang, Yong Huang, Shuai Yao, Bang Yeon Hwang, Wanying Wu, Dean Guo
Journal: Acta Pharmaceutica Sinica B (2019)

Twenty-one protostane-type triterpenoids with diverse structures, including nine new compounds (1–9), were isolated from the of Alisma plantago-aquatica Linn. Structurally, alisolides A‒F (1–6), composed of an oxole group coupled to a five-membered ring, represent unusual C-17 spirost protostane-type triterpenoids. Alisolide H (8) is a novel triterpenoid with an unreported endoperoxide bridge. Alisolide I (9) represents the first example of 23,24-acetal triterpenoid. Their structures were elucidated based on spectroscopic analysis, wherein the absolute configurations of 4‒6, 8 were further confirmed by the Mo2(OAc)4-induced ECD method. Furthermore, all isolates were evaluated for their inhibitory effects on LPS-induced NO production in Caco-2 cells, and all the compounds showed remarkable inhibitory activities, with IC50 values in the range of 0.76–38.20 μmol/L.
The blueprint of life
Authors: David Burne
Journal: BMJ (2012)

Fifty years ago, on 10 December 1962, the Nobel prize for physiology and medicine was presented to three scientists—Francis Crick, James Watson, and Maurice Wilkins. Between them, they had elucidated the structure and created the first model of one of the most important molecules in biology, deoxyribonucleic acid (DNA). This scientific trio had effectively discovered the blueprint of life.

In 1968, James Watson wrote The Double Helix , his version of the events surrounding the breakthrough. Contrary to what you might imagine, the book is far from dry or a difficult read. It documents not only Watson and Crick’s scientific progress, but also the personality clashes and ruthless behaviour of competing scientists scrapping for the same prize. …
Box 1 Criticisms of the Situational Judgement Test
Authors: Jason Walsh and Benjamin Harris
Journal: BMJ (2013)

Ability to discriminate —The final SJT pilot used seven tests of 60 questions and was taken by 6782 final year medical students. All tests showed a narrow spread of scores, with mean scores ranging from 399 to 414 points (78%-81%) and standard deviations ranging from 17 to 20 points. Candidates’ scores tended not to stray far from the mean, and the discriminatory power of the test is low. If candidates are split into deciles, as was done in the pilot tests, a difference of 1% will span a …
Isometric exercise for acute pain relief: is it relevant in tendinopathy management?
Authors: Karin Gravare Silbernagel, Bill T Vicenzino, Michael Skovdal Rathleff, Kristian Thorborg
Journal: British Journal of Sports Medicine (2019)

Isometric exercise as an initial treatment and in-season pain management for tendinopathies has become the latest trend, yet clear evidence in support of this approach is lacking. This new approach is based on a small cross-over study (n=6)1 and a small randomised control trial (n=20)2 comparing isometric and isotonic muscle contraction by Dr Ebonie Rio and colleagues. They reported substantial, acute effects of isometric exercise on pain in patients with patellar tendinopathy, which was greater than seen with isotonic exercise. While the pain relieving response of isometrics in the first trial1 was dramatic and homogenic, the pain relief response of the second trial2 was much more heterogenic. Based on these results an isometric management approach was quickly extrapolated to other tendons, as evinced in a popular recently updated sports medicine textbook.3 We contend that three important questions need to be answered before isometric exercise is widely adopted as standard valid first step in tendinopathy management.

Does …
CRISPR directed evolution of the spliceosome for resistance to splicing inhibitors
Authors: Haroon Butt, Ayman Eid, Afaque A. Momin, Jeremie Bazin, Martin Crespi, Stefan T. Arold, Magdy M. Mahfouz
Journal: Genome biology (2019)

Increasing genetic diversity via directed evolution holds great promise to accelerate trait development and crop improvement. We developed a CRISPR/Cas-based directed evolution platform in plants to evolve the rice (Oryza sativa) SF3B1 spliceosomal protein for resistance to splicing inhibitors. SF3B1 mutant variants, termed SF3B1-GEX1A-Resistant (SGR), confer variable levels of resistance to splicing inhibitors. Studies of the structural basis of the splicing inhibitor binding to SGRs corroborate the resistance phenotype. This directed evolution platform can be used to interrogate and evolve the molecular functions of key biomolecules and to engineer crop traits for improved performance and adaptation under climate change conditions.
Abstract P4-01-12: Low peripheral blood CD4/CD8 ratio at the time of surgery is a negative long-term prognostic factor in women with early stage breast cancer
Authors: MJM Magbanua, C Yau, JH Scott, L van't Veer, JW Park, L Esserman, M Campbell
Journal: Cancer Research (2019)

Abstract It is hypothesized that cancer prognosis may be related to the functional status of the immune system. We examined the correlation between peripheral blood CD4/CD8 ratio measured at the time of surgery and clinical outcome in patients diagnosed with early stage breast cancer. Patient and Methods Peripheral blood from 57 treatment-naïve early breast cancer patients, not eligible for neoadjuvant chemotherapy, was collected on the day of definitive surgery. CD4+ and CD8+ T cells were enumerated using flow cytometry and the ratio between the two immune cell populations was calculated. Cox regression analyses were performed to determine the relationship between CD4/CD8 ratio vs. distant disease-free survival (DRFS), breast cancer-specific survival (BCSS) and overall survival (OS). The median follow-up times were 10.1 years (range: 0.4-17.5) and 15.0 (range: 1.0-18.5) for DRFS and BCSS/OS, respectively. Results The patients' mean age at diagnosis was 54 years old (range: 31-78). 82% were hormone receptor-positive, 21% HER2-positive, and 61% node-negative. The median CD4/CD8 ratio was 2; and a ratio ≤ 2 was considered low. CD4/CD8 ratio was not associated with any of the clinicopathologic variable examined. Multivariate analysis using a survival model that adjusted for potential confounding factors (age, tumor size, grade, stage, hormone receptor, HER2, lymph-node status) revealed that patients with low CD4/CD8 ratio have statistically significant increased risk of distant recurrence (DRFS HR 5.3, Wald p=0.0381) and death (OS HR 3.8 Wald p=0.0271). Conclusions Immune dysfunction at the time surgery is correlated with long-term increased risk for metastatic recurrence and death. Larger clinical studies are warranted to confirm the results of this study. Citation Format: Magbanua MJM, Yau C, Scott JH, van't Veer L, Park JW, Esserman L, Campbell M. Low peripheral blood CD4/CD8 ratio at the time of surgery is a negative long-term prognostic factor in women with early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-12.