tbuckley/cabot-search huggingface dataset:
Dependency of Cholangiocarcinoma on Cyclin D–Dependent Kinase Activity
Authors: Gunya Sittithumcharee, Orawan Suppramote, Kulthida Vaeteewoottacharn, Chumphon Sirisuksakun, Supawan Jamnongsong, Phatthamon Laphanuwat, Monthira Suntiparpluacha, Arriya Matha, Porncheera Chusorn, Pongsakorn Buraphat, Chumpot Kakanaporn, Komgrid Charngkaew, Atit Silsirivanit, Krittiya Korphaisarn, Somchai Limsrichamrern, Pinpat Tripatara, Chawalit Pairojkul, Sopit Wongkham, Somponnat Sampattavanich, Seiji Okada, Siwanon Jirawatnotai
Journal: Hepatology (2019)

Cholangiocarcinoma (CCA) is a bile duct cancer with a very poor prognosis. Currently, there is no effective pharmacological treatment available for it. We showed that CCA ubiquitously relies on cyclin-dependent kinases 4 and 6 (CDK4/6) activity to proliferate. Primary CCA tissues express high levels of cyclin D1 and the specific marker of CDK4/6 activity, phospho-RB Ser780. Treatment of a 15-CCA cell line collection by pharmacological CDK4/6 inhibitors leads to reduced numbers of cells in the S-phase and senescence in most of the CCA cell lines. We found that expression of retinoblastoma protein (pRB) is required for activity of the CDK4/6 inhibitor, and that loss of pRB conferred CDK4/6 inhibitor-drug resistance. We also identified that sensitivity of CCA to CDK4/6 inhibition is associated with the activated KRAS signature. Effectiveness of CDK4/6 inhibition for CCA was confirmed in the three-dimensional spheroid-, xenograft-, and patient-derived xenograft models. Last, we identified a list of genes whose expressions can be used to predict response to the CDK4/6 inhibitor. Conclusion: We investigated a ubiquitous dependency of CCA on CDK4/6 activity and the universal response to CDK4/6 inhibition. We propose that the CDK4/6-pRB pathway is a suitable therapeutic target for CCA treatment.
Abstract P6-02-03: Interpretation schema for optical coherence tomography images in breast tissue
Authors: KS Yemul, AM Zysk, AL Richardson, KV Tangella, LK Jacobs
Journal: Cancer Research (2019)

Abstract Purpose Optical coherence tomography (OCT) is an attractive technology for surgical imaging because it permits the real-time visualization of microscopic tissue morphology with a handheld probe without the need for exogeneous agents, tissue manipulation, ionizing radiation, or histological processing. While initial studies have shown that OCT is an effective margin-evaluation tool for breast conserving surgery (BCS), image interpretation and feature identification have not been directly studied. In this work, breast pathologies were assessed with a handheld OCT probe and the images were compared to histology. Methods Mastectomy and BCS specimens from 26 women were imaged with a handheld OCT probe, and histology slides from the same region were digitally photographed. OCT and histology images from the same region were paired by selecting the best structural matches. Because image characteristics in OCT are akin to those in ultrasound, descriptive OCT image feature terminology similar to that of ultrasound was developed. Each of these characteristics was used to select and describe OCT-histology image matches. Results In total, 2880 OCT images were acquired from 26 breast specimens, and 48 matching OCT-histology image pairs were identified. These matched image pairs illustrate tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood vessels, regular and hyperplastic ducts and lobules, cysts, fibroadenoma, IDC, ILC, DCIS, calcifications, and biopsy cavities. Differentiation between pathologies was achieved by considering feature boundaries, interior appearance, posterior shadowing or enhancement, and overall morphologic patterns. Conclusions This is the first work to systematically catalog the features of breast OCT images. The results indicate that OCT can be used to identify important structures and distinguish between benign and malignant breast pathologies. Citation Format: Yemul KS, Zysk AM, Richardson AL, Tangella KV, Jacobs LK. Interpretation schema for optical coherence tomography images in breast tissue [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 P6-02-03.
Abstract P4-01-07: A comprehensive liquid biopsy in patients undergoing neoadjuvant therapy
Authors: AC Sandoval Leon, K Medina Saenz, P Miller, A Benson, C Calfa, R Mahtani, J Slingerland, A Perez, C Vogel, F Valdes-Albini, D El-Ashry, M Lippman
Journal: Cancer Research (2019)

Abstract Background: Precision medicine is revolutionizing breast cancer (BC) care. Comprehensive liquid biopsies are a tool for personalized care in patients with locally advanced breast cancer (LABC). Identifying robust biomarkers as part of a comprehensive liquid biopsy to predict response to treatment is of immense clinical interest. Methods: After obtaining IRB approval, serial blood samples were collected from patients with LABC undergoing neoadjuvant therapy. Paired biopsies were collected prior to treatment and were sent to Foundation Medicine for next-generation sequencing (NGS). We used a sized-base microfilter technology to capture circulating tumor cells (CTCs) and circulating cancer associated fibroblasts (cCAFs). Patients with one or more CTCs or cCAFs were deemed positive for these tests. Additionally, in collaboration with Foundation Medicine, we extracted circulating tumor DNA (ctDNA) and we analyzed it using the FoundationACT platform. Patients with a detectable genomic alteration in their plasma were considered as having a positive ctDNA test. Our primary objective is to determine if a comprehensive liquid biopsy can serve as a prognostic marker of pathologic complete response (pCR). Results: For this analysis we describe our findings in the initial blood draw of the first 18 patients enrolled. The mean age is 54 years (38-70). All patients who had their tumors sequenced had a detectable mutation. Consistent with the findings of others, we found TP53 mutations to be the most prevalent at 83.3%. We found that 44% of patients had ctDNA, 68.4% had cCAFs and 78.9% had CTCs. Many patients also had clusters of cells, consisting of one cell type, or co-clusters, consisting of both. 38.9% had CTC clusters, 16.7% had cCAF clusters and 16.7% had co-clusters (CTCs and cCAFs together). Some patients with CTCs did not have cCAFs and vice versa. The number of CTCs and cCAFS did not correlate with stage of disease or receptor status. Conclusions: We describe a comprehensive liquid biopsy combining a sized-based microfilter technology for CTC and cCAFs identification and the FoundationACT platform for ctDNA analysis is feasible and these biomarkers can be detected in patients with LABC prior to the initiation of neoadjuvant therapy. Our study is accruing rapidly, and we will update our results with the longitudinal collection and the prognostic value of a comprehensive liquid biopsy at the time of the meeting. Citation Format: Sandoval Leon AC, Medina Saenz K, Miller P, Benson A, Calfa C, Mahtani R, Slingerland J, Perez A, Vogel C, Valdes-Albini F, El-Ashry D, Lippman M. A comprehensive liquid biopsy in patients undergoing neoadjuvant therapy [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 P4-01-07.
First aid apps
Authors: Richard A Field
Journal: BMJ (2013)

Survival from out of hospital cardiac arrest is poor: fewer than 10% of patients survive to hospital discharge. It is well known that good quality immediate bystander cardiopulmonary resuscitation (CPR) and early defibrillation using publicly located automated external defibrillators (AEDs) increase the chances of survival. Many bystanders are reluctant to help because they do not know what to do or fear causing further harm to the casualty. Medical students are often thought by friends and family to be the ones who would know what to do in an emergency. Plenty of medical students, however, will not feel well versed enough in first aid and CPR to deal with a life threatening emergency.

Several apps are available that teach various clinical skills including first aid and resuscitation skills. Although these are unlikely to be a surrogate for hands-on first aid training they do provide the opportunity to learn some basic lifesaving skills or brush up …
To answer or not to answer?
Authors: Emilie Green
Journal: BMJ (2012)

The feeling had just about returned to my toes after a soak in the bath after a hard day of skiing. As I took my place at the dining table for a three course meal cooked by the chalet host, I braced myself for an onslaught of questions from the other guests. Sure enough, just as I had taken my first mouthful, I heard the question “So, am I all right to have some wine if I’m taking antibiotics?”

It is difficult to know how to approach such queries as a medical student. Should …
COMPLETE INVERSION OF THE UTERUS
Authors: R A Murphy
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Matching Human Unilateral AKI, a Reverse Translational Approach to Investigate Kidney Recovery after Ischemia
Authors: Danielle E. Soranno, Hyo-Wook Gil, Lara Kirkbride-Romeo, Christopher Altmann, John R. Montford, Haichun Yang, Ani Levine, Jane Buchanan, Sarah Faubel
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Unilateral ischemia-reperfusion AKI (UiAKI) occurs during kidney-sparing surgeries, but the effect of ischemia duration on kidney injury or recovery remains unclear. Some have interpreted recent findings from a human study that described reassuring short-term outcomes after UiAKI, even with ischemia lasting up to an hour, as suggesting that the human kidney is remarkably tolerant to prolonged ischemia. Using a murine model matched to parameters of that human study, the authors described longer-term histologic and functional outcomes 14 and 28 days after UiAKI, finding increased fibrosis and reduced GFR in the injured kidney that corresponded to the duration of ischemia. These findings demonstrate that the duration of ischemia affects outcomes, including long-term kidney scarring and functional decline, and that short-term findings can be falsely reassuring. Background The duration of renal ischemia that is associated with (or leads to) renal injury in patients is uncertain, and a reverse translational research approach has been proposed to improve animal models of AKI to facilitate clinical translatability. We developed a two murine models of unilateral renal ischemia to match a recently published human study that investigated renal injury after unilateral renal ischemia during partial nephrectomy. Methods Eight 10-week-old C57BL/6 male mice underwent left UiAKI or sham procedure, with or without intra-operative ice packs. Functional, histological, and biomarker outcomes were followed at 2, 6 and 24 hours, or 14 or 28 days later. The 14 and 28 day cohorts were duplicated such that contralateral nephrectomy could be performed 3 days prior to sacrifice with functional measurements obtained to isolate the glomerular filtration rate of the injured kidney. Results The short-term outcomes correlated with the human study findings with urine and serum biomarkers of injury peaking around 24 hours and then normalizing, and reassuring immediate histological outcomes. Functional and histological outcomes at the later time-points (14 and 28 days) demonstrate an increase in fibrosis markers, and a reduction in glomerular filtration rate in the injured kidney, corresponding to the duration of ischemia, while serum and urine biomarkers remained reassuring. Conclusions Our findings suggest that clinically available biomarkers of renal function are falsely reassuring against long-term injury following UiAKI, and that the duration of ischemia correlates with impaired function and increased fibrosis.
Transparent Disclosure of Conflicts Of Interest—Reply
Authors: Howard Bauchner
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 19200: A Highly Efficient in vitro Smooth Muscle Cells Differentiation System From Human Pluripotent Stem Cells-Derived Neural Crest Stem Cells
Authors: Wei Xiong, Ping Qiu, Jian Gong, Y Eugene Chen, Bo Yang
Journal: Circulation (2017)

Introduction: Most proximal aortic aneurysms, including aortic root, ascending aorta and arch, are due to aortopathy. The proximal aorta is populated by the smooth muscle cells (SMCs) originated fr...
Abstract P2-13-07: Efficacy of short-course adjuvant trastuzumab in early stage breast cancer
Authors: M Saifo, M Nikoula
Journal: Cancer Research (2019)

Abstract Background: A total of 12 months adjuvant Trastuzumab is still the optimal choice for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Still, the adjuvant short course 9-week trastuzumab may be considered as a cost-effective and safe option in developing countries such as Syria. Purpose: The primary objective was disease-free survival after short course adjuvant Trastuzumab therapy in early breast cancer at AI-Bairouni university hospital compared with 6 month of adjuvant trastuzumab , the secondary objective was assessing toxicities especially cardiac toxicity. Patients and methods: Women with histologically confirmed HER2 positive BC with either positive or negative hormone receptor of stages IA,IIA,IIB,IIC,IIIA,IIIB and IIIC were eligible for the study . Patients were assigned to 2 groups . The initial systemic treatment was similar in the 2 groups . Thereafter, no further Trastuzumab or chemotherapy was administered in Arm A; 90 patients (loading dose 4 mg/kg; then 2mg/kg weekly to complete 9 weeks of T), whereas in Arm B that included 157 patients single-agent T was administered to complete 6 months (loading dose 8 mg/kg then 6 mg/kg every 3 weeks) . The LVEF was measured pretreatment, and every 3 months afterword . Results: After a median follow up of 24 months DFS was 89.06% and 89.81% in groups A and B respectively (P=0.11).No obvious side effects have been noticed during the follow up period in group A. otherwise congestive heart failure was reported in 2.55% of group B patients . Conclusion: Short course 9 weeks adjuvant Trastuzumab achieved a good 2 years disease-free survival rate (DFS) compared to 6 month of treatment, with acceptable toxicity and good tolerability for treated patients with early-stage invasive breast cancer. Patients are being monitored for a longer follow up period. Citation Format: Saifo M, Nikoula M. Efficacy of short-course adjuvant trastuzumab in 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 P2-13-07.
Abstract 17117: Burden of Catastrophic Health Expenditures for Acute Myocardial Infarction and Stroke Hospitalizations Among Uninsured in the United States
Authors: Rohan Khera, Jonathan Hong, Anshul Saxena, Alejandro Arrieta, Salim S Virani, Ron Blankstein, James A de Lemos, Harlan M Krumholz, Khurram Nasir
Journal: Circulation (2017)

Background: Acute myocardial infarction (AMI) and stroke represent unanticipated major healthcare events that require emergent and expensive care. Given their potential financial implications among...
What you need to know about the seven day NHS
Authors: Peter Hateley
Journal: BMJ (2015)

Over the past two decades there has been a rise in the opening hours of many industries, such as supermarkets, transport, and retail, where you can access a broad range of services 24 hours a day. Despite this, many parts of NHS care are reduced at weekends, with primary care commonly unavailable and hospital staffing often run at lower levels.

However, this may be about to change. In his first major speech after being re-elected in May 2015, David Cameron reiterated the government’s drive towards providing a comprehensive seven day NHS service, which was initially set out in the Conservative Party’s 2010 manifesto. His speech included plans to open general practitioner surgeries from 8 am to 8 pm every day, alongside better provision in seven day hospital care.

Although extending the opening hours of the NHS will be a popular policy for the public, how will it work in practice and what will be the effect on the staff being asked to deliver it?

The move towards a more comprehensive seven day NHS has been driven by a combination of political and patient safety factors. Increasing evidence suggests that care is less effective at weekends. Often quoted figures in a study published by the Journal of the Royal Society of Medicine reported that patient death rates from weekend admissions compared with Wednesdays were 16% higher on Sundays and 11% higher on Saturdays.1 Evidence from Dr Foster Intelligence also links higher death rates at weekends to fewer senior doctors being present on the wards.2 These figures have raised serious questions about weekend care, even though the reasons behind the numbers have been contested. The evidence prompted NHS England, the national independent body set up to help improve patient outcomes, to initiate a Seven Days a Week forum in 2013. …
Abstract B09: Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma.
Authors: Francesca Cottini, Teru Hideshima, Paul Richardson, Kenneth Anderson, Giovanni Tonon
Journal: Clinical Cancer Research (2015)

Abstract This abstract is being presented as a short talk. A full abstract is printed in the Proffered Abstracts section (PR04) of the Conference Proceedings. Citation Format: Francesca Cottini, Teru Hideshima, Paul Richardson, Kenneth Anderson, Giovanni Tonon. Exploiting oncogene-induced DNA replicative stress as synthetic lethal approach to target myeloma. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B09.
A tragic life
Authors: Shermin Merali
Journal: BMJ (2011)

She’s Come Undone

Wally Lamb

First Published 1992; Washington Square Press; 416 pp; £5.79; ISBN 0 684 86009 0 

Dolores Price, the misunderstood, self loathing, and eager to please fictitious heroine in Wally Lamb’s She’s Come Undone , illustrates how a child can go from fun loving and flamboyant to grossly disturbed. The book is narrated by 40 year old Dolores, who begins her story in 1956. We are introduced to a lovely little girl who is similar to many girls her age. Her parents struggle with infidelity, financial woes, and a stillborn baby boy. Dolores’s mother was not given the chance to mourn her son’s death and has …
Sweet anatomy: how a medical student is using confectionery to make learning anatomy fun
Authors: Mike McCormick
Journal: BMJ (2015)

In a sweet shop you see strawberry laces, candy hearts, and foam bananas. But when I’m in a sweet shop I see capillaries, myocardium, and the beginnings of a pancreas and I start searching for some blue raspberry laces so I can finally incorporate deoxygenated blood vessels. Don’t worry, it’s me that’s the weird one, but let me explain a bit about my strange hobby.

My name is Mike McCormick. I’m a first year medical student at the University of Glasgow and a physiology graduate from the University of Edinburgh. My project Candy Anatomy started in September 2014, during the first few weeks of medical school, and since then it has spiralled out of control.

Having taken a few years away from academia, I decided to surround myself with everything medical …