tbuckley/cabot-search huggingface dataset:
Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content
Authors: Yuan Luo, Parinaz Abiri, Shell Zhang, Chih-Chiang Chang, Amir H. Kaboodrangi, Rongsong Li, Alex Bui, Rajesh Kumar, Mary Woo, Zhaoping Li, René R. Sevag Packard, Yu-Chong Tai, Tzung K. Hsiai
Journal: Theranostics (2018)

Introduction:Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD).While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements.Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content.To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry.To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age-and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets).Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation.We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²). Conclusion:We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content.Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome.
Certificate of basic competence in electrocardiographic interpretation
Authors: Denise Stevens
Journal: BMJ (2008)

The electrocardiogram (ECG) is the investigation of first choice in patients presenting with chest pain, dizziness, syncope, or palpitation. Most of us learn the basics of interpreting an ECG as medical students on a fairly ad hoc basis. As a consequence, we tend to develop only a limited understanding of how and why the ECG is produced, and how it can vary in the face of cardiac disease or dysfunction. We therefore come to rely largely on pattern recognition, which runs the risk of missing or misinterpreting diagnoses.

The aim of the course is to develop proficiency in understanding and interpreting ECGs. It is taught by Derek Rowlands, a retired consultant …
Abstract P1-09-09: Efficacy of estrogen receptor β agonists in the prevention of breast cancer progression to therapy resistance
Authors: K Ramasamy, C Samayoa, NK Krishnegowda, RK Vadlamudi, RR Tekmal
Journal: Cancer Research (2018)

Abstract Estrogen plays an important role in the initiation and progression of breast cancer (BCa). Approximately, 70% of breast tumors are estrogen receptor (ER) positive at the time of presentation. Endocrine therapy using aromatase inhibitors (AI), or anti-estrogen (AE) molecules are widely used for treating ER+ve BCa. However, their efficacy is limited by intrinsic and acquired therapy resistance and most patients develop resistance to these drugs. The transcriptional effects of estrogen are mediated by two ERs (ERα and ERβ) and both are expressed in normal breast tissue. Unlike ERα, ERβ functions as tumor suppressor. However, role of ERβ specific agonists in the prevention of BCa progression remains elusive. In this study, we investigated the effectiveness of two ERβ agonists (S-Equol and LY500307) in the prevention of BCa progression using endocrine therapy sensitive (MCF7-aro) and letrozole resistant (MCF7-aro-LTLT) cells. Our results demonstrated that treatment with ERβ agonists inhibit short-and long-term growth of both endocrine therapy sensitive and resistant BCa cells. In addition, ERβ agonists treatment inhibited invasion and migration of both MCF7-aro and MCF7-aro-LTLT cells. Importantly, cell cycle analysis revealed that ERβ agonists induced cell cycle arrest. Our gene microarray analysis demonstrated that both ERβ agonists significantly modulated genes involved in the cell cycle progression, DNA replication and cell death pathways. Further, gene enrichment analysis of differentially expressed genes revealed that genes involved in the cell cycle checkpoints emerged as significant pathway modulated by ERβ agonists treatment in MCF7-aro cells. Interestingly, in letrozole-resistant MCF7-aro cells, DNA replication was significantly affected by ERβ agonists treatment. Pathway analysis also identified enrichment for chemokine signaling pathways. We confirmed pathway analysis by qRT-PCR and western blot analysis. Accordingly, treatment of in vivo syngeneic xenografts with ERβ agonists significantly inhibited BCa progression. Collectively, these results from this study suggest that ERβ agonists have potential to prevent the progression of BCa progression. Citation Format: Ramasamy K, Samayoa C, Krishnegowda NK, Vadlamudi RK, Tekmal RR. Efficacy of estrogen receptor β agonists in the prevention of breast cancer progression to therapy resistance [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-09-09.
Isoform-Selective Phosphatidylinositol 3-Kinase Inhibition in Cancer
Authors: Johann S. Bergholz, Thomas M. Roberts, Jean J. Zhao
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phosphatidylinositol 3-Kinase α–Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study. February 05, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2017.77.0891 Journal of Clinical Oncology - published online before print March 8, 2018 PMID: 29517943 Isoform-Selective Phosphatidylinositol 3-Kinase Inhibition in Cancer Johann S. BergholzxJohann S. BergholzSearch for articles by this author, Thomas M. RobertsxThomas M. RobertsSearch for articles by this author, and Jean J. ZhaoxJean J. ZhaoSearch for articles by this author Show More Johann S. Bergholz, Thomas M. Roberts, and Jean J. Zhao, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2017.77.0891 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Phosphatidylinositol 3-Kinase α–Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study
Dying for a kip: the importance of sleep medicine
Authors: Chris Hanning
Journal: BMJ (2005)

Medical students get about two minutes teaching on it, there is no formal training in the United Kingdom, and there is only a handful of dedicated consultants. It9s time we woke up to the merits of sleep medicine say <b>Andy Currie</b>, <b>Ed Peile,</b> and <b>Chris Hanning</b>
Association of Patient Satisfaction With Medical Scribe Use in an Academic Dermatology Practice
Authors: Vinod E. Nambudiri, Alice J. Watson, Mitchell H. Rubenstein, Thomas S. Kupper, Fei-Shiuann Clarissa Yang
Journal: JAMA Dermatology (2018)

dated methods for evaluating dermatology-specific HRQOL, self-reported measure of anxiety and depression, and perception of disease, respectively. 4,5Scoring for the measures is described in the Table .For comparison between groups, we used the Pearson correlation coefficient or χ 2 test, as appropriate.All given P values are 2-tailed and P <.05 indicates statistical significance.Statistical analysis was conducted with SPSS, version 19.0 (SPSS Inc).
EDITOR's CHOICE: It's a wrap
Authors: Sabina Dosani
Journal: BMJ (2007)

I remember it vividly. Three examiners, asking questions. I was mumbling incoherently, feeling self conscious. No wonder I felt awkward—I was naked. No, this isn't the old style examination for MRCPsych, but a nightmare I had during my specialist registrar training. You don't have to be a …
Cardiovascular events in ankylosing spondylitis: a 2018 meta-analysis
Authors: Sylvain Mathieu, Martin Soubrier
Journal: Annals of the Rheumatic Diseases (2018)

In an article published in the Annals of the Rheumatic Diseases , Schieir et al 1 reported a trend of increased cardiovascular risk in patients with ankylosing spondylitis (AS). In this letter, we wish to add data to support the conclusions of that article. We performed an updated meta-analysis to investigate the risks of myocardial infarction (MI) and stroke in patients with AS and controls.

We searched PubMed to find reports of interest, published up to February 2018. We included all observational or case/control studies that reported rates of MI or stroke. We calculated the incidences of MI and stroke in a meta-analysis of proportions (inverse variance method) and expressed them in terms of …
An integrative functional genomics framework for effective identification of novel regulatory variants in genome–phenome studies
Authors: Junfei Zhao, Feixiong Cheng, Peilin Jia, Nancy Cox, Joshua C. Denny, Zhongming Zhao
Journal: Genome Medicine (2018)

Genome–phenome studies have identified thousands of variants that are statistically associated with disease or traits; however, their functional roles are largely unclear. A comprehensive investigation of regulatory mechanisms and the gene regulatory networks between phenome-wide association study (PheWAS) and genome-wide association study (GWAS) is needed to identify novel regulatory variants contributing to risk for human diseases. In this study, we developed an integrative functional genomics framework that maps 215,107 significant single nucleotide polymorphism (SNP) traits generated from the PheWAS Catalog and 28,870 genome-wide significant SNP traits collected from the GWAS Catalog into a global human genome regulatory map via incorporating various functional annotation data, including transcription factor (TF)-based motifs, promoters, enhancers, and expression quantitative trait loci (eQTLs) generated from four major functional genomics databases: FANTOM5, ENCODE, NIH Roadmap, and Genotype-Tissue Expression (GTEx). In addition, we performed a tissue-specific regulatory circuit analysis through the integration of the identified regulatory variants and tissue-specific gene expression profiles in 7051 samples across 32 tissues from GTEx. We found that the disease-associated loci in both the PheWAS and GWAS Catalogs were significantly enriched with functional SNPs. The integration of functional annotations significantly improved the power of detecting novel associations in PheWAS, through which we found a number of functional associations with strong regulatory evidence in the PheWAS Catalog. Finally, we constructed tissue-specific regulatory circuits for several complex traits: mental diseases, autoimmune diseases, and cancer, via exploring tissue-specific TF-promoter/enhancer-target gene interaction networks. We uncovered several promising tissue-specific regulatory TFs or genes for Alzheimer's disease (e.g. ZIC1 and STX1B) and asthma (e.g. CSF3 and IL1RL1). This study offers powerful tools for exploring the functional consequences of variants generated from genome–phenome association studies in terms of their mechanisms on affecting multiple complex diseases and traits.
Immunotherapy in Advanced Renal Cancer — Is Cure Possible?
Authors: Brendan D. Curti
Journal: New England Journal of Medicine (2018)

Treatment for advanced renal-cell carcinoma has traced a remarkable arc during the past 25 years. In the 1990s, options included interferon, interleukin-2, megestrol, and 5-fluorouracil chemotherapy.1 Although a small proportion of patients had durable regression of renal-cell carcinoma with interleukin-2,2 no randomized, controlled clinical trials showed a survival benefit with any therapy in that era. Knowledge about von Hippel–Lindau gene mutations in renal-cell carcinoma and the downstream up-regulation of hypoxia-inducible factors led to insights about how these pathways influence angiogenesis. This led to the development of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors of multiple receptors . . .
Aquagenic wrinkling of the palms in patients with cystic fibrosis
Authors: H. Kaiser, N. Brustad, T. Pressler, A. Bygum
Journal: British Journal of Dermatology (2018)

Aquagenic wrinkling of the palms (AWP) is a condition characterized by oedema, confluent white papules and excessive wrinkling of the palms after few minutes exposure to water.The phenomenon may be associated with pain, numbness and pruritus 1,2 .It was first noticed and described in 1974 in children with cystic fibrosis (CF) by a paediatrician R.B. Elliott 3 .Case reports and some smaller studies have later confirmed this association 1,2,4,5 .CF is an autosomal recessive inherited abnormality caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leading to abnormal transport of chloride over epithelial membranes 6 .
The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms
Authors: Bob G. Schultz, Denise K. Patten, Daniel J. Berlau
Journal: Translational Neurodegeneration (2018)

Nearly 30% of adults 40 years and older in the United States are on a statin. Their widespread use heightens the importance of careful consideration of their varied effects on the body. Although randomized controlled trials have not confirmed cognitive impairing effects with statins, continuing evidence suggests statins have the ability to cause reversible cognitive impairment in some patients. Paradoxically, statins have also been shown to decrease the risk of dementia, Alzheimer's disease, and improve cognitive impairment in some cases. However, randomized controlled trials have similarly failed to find the beneficial effect. Supporting evidence for both claims is compelling whereas known limitations of the clinical trials may explain the lack of findings. This narrative review aims to explain why there is still controversy and how both effects can, and may, be possible. The mechanisms that have been hypothesized for each effect are seemingly independent from one another and may explain the contradicting results. Being mindful of the complex effects of statins, health care providers need to be able to identify patients who are at risk for or already experiencing cognitive impairment from statin use while also identifying those who could potentially decrease their risk of dementia with statins.
Pan-Cancer assessment of tumor mutational burden using a comprehensive genomic profiling assay.
Authors: Donna Nichol, Siân Jones, Samuel V. Angiouli, Laurel Keefer, Monica Nesselbush, Naomi Sengamalay, James White, John Simmons, Luis A. Diaz, Victor E. Velculescu, Mark Sausen
Journal: Journal of Clinical Oncology (2018)

157 Background: Checkpoint inhibitors (CPIs) have been approved for frontline or subsequent therapies in several indications over the last few years. While patient response can be remarkably durable, many patients do not benefit. Current clinical biomarkers of response to CPIs include microsatellite instability (MSI) and PD-L1 expression. While a proportion of many solid tumors display microsatellite instability, the prevalence is often very low. Similarly, while clinically informative, PD-L1 expression alone is not sufficient to predict therapeutic outcomes with high accuracy. The lack of predictive biomarkers for response highlights the need for improved biomarkers with greater prevalence across tumor types to predict response to CPIs. Multiple clinical studies have revealed that high tumor mutational burden (TMB) is associated with improved clinical response. Methods: Here, we describe the development of a method that can be used to accurately infer mutational burden from a discrete set of targeted regions of interest across the exome. Initially, we performed an assessment of the accuracy across multiple bioinformatics methods for identification of individual sequence mutations (SBS/indels) using orthogonally validated data together with publicly available TCGA whole-exome sequencing data. The targeted regions were then isolated from these datasets to demonstrate analytical performance across several different solid tumor types. Finally, we evaluated independent non-small cell lung cancer (NSCLC) and colorectal carcinoma (CRC) cohorts to demonstrate the analytical accuracy of the assay and bioinformatics approach for determination of mutational burden when compared to whole exome sequencing. Results: In summary, high concordance was observed across a large dynamic range of mutations per megabase of coding sequence. Conclusions: Our data indicate that the assay can be used to accurately determine mutational burden in a range of tumor types, across a spectra of potential mutational burden cut-offs using automated, complex mutation identification algorithms.
Abstract P4-09-09: Correlation of breast cancer index (BCI) predictive (HoxB13/IL17BR) results to nodal status and hormone receptor expression in early stage HR+ breast cancer
Authors: A Elias, MA Israel, Y Zhang, CA Schnabel, J Mayordomo
Journal: Cancer Research (2018)

Abstract Background: The HoxB13/IL17BR (H/I) ratio, the endocrine response component of the Breast Cancer Index (BCI), was initially discovered in patients with LN- breast cancer, and validated as a predictive biomarker of benefit from extended endocrine therapy (EET) in a cohort from MA.17 that included both LN- and LN+ patients. Here, correlative analyses were performed to further characterize BCI Predictive (H/I) results with nodal status and quantitative hormone receptor expression. Methods: Analyses were performed using data from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database that contains &amp;gt;50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice (N=19,126). Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of these cases. Cases from patients with confirmed nodal status were analyzed. Chi-squared tests and ANOVA were used to compare results between subgroups. Results: Analyses included 13,114 patients (median age 58.9y; range 23-92y); 9562 were LN- and 3552 LN+. The distribution of individual H/I scores and proportion of patients classified as High H/I were generally similar in LN- and LN+ patients, though a modestly greater proportion of LN+ patients (46.2%) were classified as High H/I compared to LN- patients (42.0%; P&amp;lt;0.01). In both LN- and LN+ patients, median quantitative ER (qER) expression was slightly higher in patients with Low H/I than with High H/I; qPR showed the same trend but with a larger magnitude (P&amp;lt;0.0001 for both). Similar results were observed for percent positive staining by IHC (P&amp;lt;0.0001). In both LN- and LN+ patients, H/I showed a weak negative correlation with qER (LN-, 0.227; LN+, 0.192) and qPR expression (LN-, 0.311; LN+, 0.311). Conclusion: In this study to evaluate potential biological correlates of BCI, results showed that H/I biomarker activity did not appear to be dependent on nodal status. Secondly, although ER expression is an established biomarker for endocrine sensitivity, High H/I status did not correlate with increased quantitative ER and PR expression. The H/I ratio may be an independent new marker for endocrine sensitivity independent of the strength of ER expression. Citation Format: Elias A, Israel MA, Zhang Y, Schnabel CA, Mayordomo J. Correlation of breast cancer index (BCI) predictive (HoxB13/IL17BR) results to nodal status and hormone receptor expression in early stage HR+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-09.
Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing
Authors: Mohamed Abdelrahman, Faiz A. Subzposh, Dominik Beer, Brendan Durr, Angela Naperkowski, Haiyan Sun, Jess W. Oren, Gopi Dandamudi, Pugazhendhi Vijayaraman
Journal: Journal of the American College of Cardiology (2018)
Eliezer Rachmilewitz (1935–2017)
Authors: Ioav Cabantchik, Martina Muckenthaler, Clara Camaschella
Journal: HemaSphere (2018)

Eliezer Rachmilewitz (1935–2017).The hematology community mourns the sudden death of Professor Eliezer Rachmilewitz, who passed away on December 17, 2017. Spending most of his career in the Hadassah Medical Center in Jerusalem, Eliezer was one of the pioneers of thalassemia research, and one of the first to recognize the relationship between oxidative stress and iron overload in a variety of hematological disorders. He had a passion for medical research and until the last moments of his life he shared it with colleagues and students. He always showed an incredible learning ability and enthusiasm for new developments in basic and clinical research. Eliezer had an outgoing personality with a flair for approaching and attracting people and offering his professional assistance to those in need. He was endowed with a special skill for liaising between investigators specializing in different areas of biomedicine and, as such, he generated fruitful collaborations with numerous people worldwide, including those in Israel, the Palestinian territories, and Arab countries. Eliezer was the son of one of the legendary scholars and physicians who founded the Hadassah Medical Center in Israel as both and academic and clinical institution of worldwide reputation, and he continued that tradition of excellence until very recently. Eliezer will undoubtedly be missed by his family and by the extended biomedical community.