tbuckley/cabot-search huggingface dataset:
Mimicking Factor VIII to Manage the Factor VIII–Deficient State
Authors: Margaret V. Ragni
Journal: New England Journal of Medicine (2018)

Hemophilia A is an X-linked disorder caused by defective factor VIII, which until now has involved factor VIII replacement to treat and prevent bleeding in joints, muscles, and other body cavities. Although factor VIII replacement is effective, the treatment burden is high, because intravenous access occurs several times weekly and the therapy is complicated by inhibitor antibody development in up to 30% of patients. Thus, interest is intense in new therapeutic agents for the restoration of hemostasis in patients with hemophilia. One such agent is the factor VIII mimic emicizumab (Hemlibra), which was investigated in a trial by Mahlangu et . . .
Abstract 17709: Deviation From Dosing Labels of Non-vitamin K Antagonist Oral Anticoagulants May be Associated With Reduced Effectiveness or Safety
Authors: Xiaoxi Yao, Nilay D Shah, Lindsey R Sangaralingham, Bernard J Gersh, Peter A Noseworthy
Journal: Circulation (2016)

Introduction: Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in atrial fibrillation (AF) patients with clinically significant renal impairment. We aimed to inve...
Engineering the Direct Repeat Sequence of crRNA for Optimization of FnCpf1-Mediated Genome Editing in Human Cells
Authors: Li Lin, Xiubin He, Tianyuan Zhao, Lingkai Gu, Yeqing Liu, Xiaoyu Liu, Hongyan Liu, Fayu Yang, Mengjun Tu, Lianchao Tang, Xianglian Ge, Changbao Liu, Junzhao Zhao, Zongming Song, Jia Qu, Feng Gu
Journal: Molecular Therapy (2018)

FnCpf1-mediated genome-editing technologies have enabled a broad range of research and medical applications. Recently, we reported that FnCpf1 possesses activity in human cells and recognizes a more compatible PAM (protospacer adjacent motif, 5′-KYTV-3′), compared with the other two commonly used Cpf1 enzymes (AsCpf1 and LbCpf1), which requires a 5′-TTTN-3′ PAM. However, due to the efficiency and fidelity, FnCpf1-based clinical and basic applications remain a challenge. The direct repeat (DR) sequence is one of the key elements for FnCpf1-mediated genome editing. In principle, its engineering should influence the corresponding genome-editing activity and fidelity. Here we showed that the DR mutants [G(−9)A and U(−7)A] could modulate FnCpf1 performance in human cells, enabling enhancement of both genome-editing efficiency and fidelity. These newly identified features will facilitate the design and optimization of CRISPR-Cpf1-based genome-editing strategies.
Congenital Penile Rhabdomyosarcoma on FDG PET/CT
Authors: Chenxi Wu, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2018)

Primary penile malignancy is uncommon. Congenital primary penile rhabdomyosarcoma diagnosed in an infant is extremely rare. We present the FDG PET/CT findings in a 1-month-old boy with penile mass. The images showed hypermetabolic lesion at the base of the penis and left inguinal lymph node. Pathological examination demonstrated rhabdomyosarcoma.
Peter John Donald Whittaker
Authors: Grant Kelly, Sara Kelly
Journal: BMJ (2018)

After Cambridge, Peter John Donald Whittaker went to the Westminster Hospital, where he won the Bulkeley medal and met Bryony, his future wife. They both went to Chichester for their second house jobs.

Peter joined the local general practitioner training scheme, and afterwards he and Bryony started working as GPs at the Lavant Road Surgery in Chichester in 1980, where he practised until 2016.

Having been a scholar at Cambridge, …
Abstract 13566: A Novel New Chemical Entity, Gemcabene, Shows Significant Lipid Regulation in PPAR-α Knock-out Mice, Supporting a Mechanism Independent of PPAR-α
Authors: Charles L Bisgaier, Rai Ajit Srivastava
Journal: Circulation (2015)

Background: In vitro and cell-based assays with a lipid lowering agent, gemcabene (Gem), ruled out a direct activation of PPAR-α, although some PPAR-α target genes were modulated in vivo. Therefore, PPAR-α may not be required for the in vivo lipid lowering efficacy of Gem. Experiment &amp; Results: WT and PPAR-α KO mice were administered Gem (0.3%), Wy14643 (0.1%), a reference PPAR-α agonist, and a clinical lipid regulator, Gemfibrozil (0.3%) as diet admixtures for 8 days. PPAR-α KO mice exhibited a phenotype consistent with absence of PPAR-α, such as increased plasma triglycerides (TG), VLDL-C, LDL-C, HDL-C, and apoCIII. Hepatic apoCIII mRNA (negatively regulated by PPAR-α) showed upregulation in PPAR-α KO mice compared to WT. In WT mice, there was no change in liver to body weight ratio in the Gem-treated group, but a marked increase (212%) in the Wy14643-treated-group and marginal increase (22%) in gemfibrozil-treated mice. In WT, hepatomegaly was observed only in the Wy14643-treated group, which was associated with peroxisome proliferation, and a 20-fold increase in the PPAR-α target gene, acyl CoA oxidase (ACO). Absence of hepatomegaly in the Wy14643-treated PPAR-α KO mice and no change in ACO mRNA supported PPAR-α mediated effect of Wy14643. In WT, Gem and gemfibrozil showed a 3-fold increase in ACO mRNA. Gem lowered VLDL-C (-47%), LDL-C (-22%), and TG (-46%) in PPAR-α KO mice, suggesting a PPAR-α independent effect on circulating lipids. Wy14643 and Gem significantly reduced apoCIII by -39% and -24% in WT, and -20% and -16% in PPAR-α KO mice, respectively. ApoCIII mRNA was reduced -12% (NS) in Gem-treated and significantly by -46% in Wy14643-treated WT-mice. In KO mice, apoCIII mRNA was reduced by -8% (NS) by Gem and significantly by -20% by Wy14643. ApoCIII mRNA is a direct target of PPAR-α while plasma apoCIII level is influenced by several factors. Wy14643 induced hepatic LPL mRNA in WT, but not in PPAR-α KO mice. Interestingly, hepatic PPARγ expression showed increased level in the PPARα KO mice, suggesting the regulation of the two isoforms may be interdependent. Conclusions: Taken together, these studies demonstrate that the lipid lowering efficacy of Gem occurs in a PPAR-α -independent manner in vivo.
Outcome-based interpretation of early interim PET in advanced-stage Hodgkin lymphoma
Authors: Carsten Kobe, Helen Goergen, Christian Baues, Georg Kuhnert, Conrad-Amadeus Voltin, Josée Zijlstra, Otto Hoekstra, Jasmin Mettler, Alexander Drzezga, Andreas Engert, Peter Borchmann, Markus Dietlein
Journal: Blood (2018)
Folk-economics: Inherited biases or misapplication of everyday experience?
Authors: Don Ross
Journal: Behavioral and Brain Sciences (2018)

Abstract Evidence for an EEA-derived domain-specific inference system must point to an active, latent representational structure. Otherwise we need to hypothesize only passive, virtual belief not over-ridden on the basis of the individual's experience. The folk economic beliefs identified by Boyer &amp; Petersen (B&amp;P), being with one exception about macroeconomics, might be virtual beliefs that people extrapolate across the micro–macro scale shift based on their experiences with markets.
Challenges of folk-economic beliefs: Coverage, level of abstraction, and relation to ideology
Authors: Zeljka Buturovic
Journal: Behavioral and Brain Sciences (2018)

There are no clear criteria regarding what kind of beliefs should count as folk-economic beliefs (FEBs), or any way to make an exhaustive list that could be filtered through such criteria. This allows the target article authors, Boyer &amp; Petersen, to cherry-pick FEBs, which results in the omission of some well-established FEBs. The authors do not sufficiently address a strong relationship between ideology and FEBs.
Encapsulation of Thermo-responsive Gel in pH-sensitive Polymersomes as Dual-Responsive Smart carriers for Controlled Release of Doxorubicin
Authors: Fatemeh Oroojalian, Maryam Babaei, Seyed Mohammad Taghdisi, Khalil Abnous, Mohammad Ramezani, Mona Alibolandi
Journal: Journal of Controlled Release (2018)
2018 update of the EULAR recommendations for the management of hand osteoarthritis
Authors: Margreet Kloppenburg, Féline PB Kroon, Francisco J Blanco, Michael Doherty, Krysia S Dziedzic, Elsie Greibrokk, Ida K Haugen, Gabriel Herrero-Beaumont, Helgi Jonsson, Ingvild Kjeken, Emmanuel Maheu, Roberta Ramonda, Marco JPF Ritt, Wilma Smeets, Josef S Smolen, Tanja A Stamm, Zoltan Szekanecz, Ruth Wittoek, Loreto Carmona
Journal: Annals of the Rheumatic Diseases (2018)

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1–3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4–8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.
Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of place of care
Authors: Kate Nambiar, Harald Seifert, Siegbert Rieg, Winfried V. Kern, Matt Scarborough, N. Claire Gordon, Hong Bin Kim, Kyoung-Ho Song, Robert Tilley, Hannah Gott, Chun-Hsing Liao, Jonathan Edgeworth, Emmanuel Nsutebu, Luis Eduardo López-Cortés, Laura Morata, A. Sarah Walker, Guy Thwaites, Martin J. Llewelyn, Achim J. Kaasch, Marina de Cueto, Isabel Morales, Jesús Rodríguez-Baño, Eu Suk Kim, Chung-Jong Kim, Chang Kyung Kang, Jung In Park, Christian Bernasch, Danuta Stefanik, Norma Jung, Martin Hellmich, Peter Wilson, Anna Reyes, Saadia Rahman, Victoria Dean, Miguel Marcos, Hugo Guillermo Ternavasio-de la Vega, Estée Török, Theodore Gouliouris, Luke Bedford, José L. Pérez, Enrique Ruiz de Gopegui, Maria Luisa Martín-Pena, Susan Hopkins, Karuna Lamarca, Beatriz Mirelis, Mercedes Gurgui Ferrer, Vance G. Fowler, Felicia Ruffin, José Miguel Cisneros Herreros, José A. Lepe, Cristina Roca, James R. Price, Angela Dunne, Laura Behar, Gavin Barlow
Journal: Journal of Infection (2018)
Abstract 19076: ATAC-seq Implicates Epigenome-wide CTCF Dissociation in the Progression of Cardiac Ischemia
Authors: Jonathan D Lee, Shin Lin, Michael P Snyder
Journal: Circulation (2015)

Introduction: Heart disease is currently the most common cause of death in the United States. In 2010 alone, over 375,000 people died of coronary heart disease, of which over 120,000 were from myocardial infarction. Due to technical challenges associated with current techniques, profiling epigenome changes due to myocardial infarction has been limited. We have optimized an assay for transposase-accessible chromatin with sequencing (ATAC-seq) protocol that circumvents these challenges and works well with frozen tissue. Hypothesis: We assessed the hypothesis that ATAC-seq would enable the identification of novel chromatin remodeling and transcription factor binding events in a murine model of cardiac ischemia. Methods: Six 10 ± 2 week old C57BL/6J mice were paired by same gender, age, and litter, and mice from these pairs were selected for either mid left anterior descending artery ligation or sham surgery, both for 30 minutes. Successful ligation was confirmed by blanching of the tissue and representative electrocardiography changes. We performed our ATAC-seq protocol on left ventricular tissues, and regions of open chromatin were determined using the Hotspot algorithm at a false detection rate of 0.5%. Gene ontology was performed with the Genomic Regions Enrichment of Annotations Tool (GREAT), and motif discovery was performed with the Multiple Em for Motif Elicitation (MEME) Suite. Results: From stringent overlap criteria were obtained 159 loci that became “open” due to ischemia and 782 loci that became “closed”. Downregulation of growth and signaling processes was determined by GREAT. MEME strongly implicated the dissociation of CCCTC-binding Factor (CTCF) due to ischemia (MEME E-score = 8.10e-235; motif identification p -value = 1.88e-18; 262/782 of “closed” loci). CTCF ChIP-seq data and footprint analysis enabled the further identification of a robust set of 189 CTCF differential binding events. Conclusions: ATAC-seq was able to identify widespread chromatin remodeling due to cardiac ischemia alone. We identified a robust set of 189 gene loci from which CTCF binding is attenuated in response to this disease state. To our knowledge, this represents the first study that has examined chromatin accessibility changes in the setting of cardiac ischemia.
Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma
Authors: Axel Bex, Laurence Albiges, Börje Ljungberg, Karim Bensalah, Saeed Dabestani, Rachel H. Giles, Fabian Hofmann, Milan Hora, Markus A. Kuczyk, Thomas B. Lam, Lorenzo Marconi, Axel S. Merseburger, Sergio Fernández-Pello, Rana Tahbaz, Yasmin Abu-Ghanem, Michael Staehler, Alessandro Volpe, Thomas Powles
Journal: European Urology (2018)
TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer’s disease
Authors: Paramita Chakrabarty, Andrew Li, Thomas B. Ladd, Michael R. Strickland, Emily J. Koller, Jeremy D. Burgess, Cory C. Funk, Pedro E. Cruz, Mariet Allen, Mariya Yaroshenko, Xue Wang, Curtis Younkin, Joseph Reddy, Benjamin Lohrer, Leonie Mehrke, Brenda D. Moore, Xuefei Liu, Carolina Ceballos-Diaz, Awilda M. Rosario, Christopher Medway, Christopher Janus, Hong-Dong Li, Dennis W. Dickson, Benoit I. Giasson, Nathan D. Price, Steven G. Younkin, Nilüfer Ertekin-Taner, Todd E. Golde
Journal: The Journal of Experimental Medicine (2018)

There is considerable interest in harnessing innate immunity to treat Alzheimer's disease (AD). Here, we explore whether a decoy receptor strategy using the ectodomain of select TLRs has therapeutic potential in AD. AAV-mediated expression of human TLR5 ectodomain (sTLR5) alone or fused to human IgG4 Fc (sTLR5Fc) results in robust attenuation of amyloid β (Aβ) accumulation in a mouse model of Alzheimer-type Aβ pathology. sTLR5Fc binds to oligomeric and fibrillar Aβ with high affinity, forms complexes with Aβ, and blocks Aβ toxicity. Oligomeric and fibrillar Aβ modulates flagellin-mediated activation of human TLR5 but does not, by itself, activate TLR5 signaling. Genetic analysis shows that rare protein coding variants in human TLR5 may be associated with a reduced risk of AD. Further, transcriptome analysis shows altered TLR gene expression in human AD. Collectively, our data suggest that TLR5 decoy receptor-based biologics represent a novel and safe Aβ-selective class of biotherapy in AD.
Acute Clinical Care for Transgender Patients
Authors: Nicole Rosendale, Seth Goldman, Gabriel M. Ortiz, Lawrence A. Haber
Journal: JAMA Internal Medicine (2018)

Transgender is an umbrella term used to describe individuals whose gender identity and/or gender expression differs from assigned sex at birth. There are an estimated 1.4 million transgender adults in the United States, and this number is increasing. Clinicians will increasingly be caring for transgender patients. Topics considered in this narrative review include terminology, how to address transgender patients, obtaining an inclusive history that takes into account gender-affirming surgery, managing hormone therapy and other clinical issues, consideration for hospitalized patients, interpreting laboratory values in the setting of hormone use, legal issues, and considerations for health systems.Best practices in caring for a transgender patient include using a patient-identified name and pronoun, using gender-neutral terminology until the appropriate term is identified by the patient, and obtaining a surgical history inclusive of an anatomic inventory. Gender-affirming hormones can modify disease-specific risk factors or confer risk for in-hospital complications. They can also cause changes in laboratory values; however, studies are limited to observational studies and case series. Some data are derived and extrapolated from cisgender populations. There are also unique systems-based concerns, including lack of procedures for standardized collection of gender identity and lack of sufficiently comprehensive electronic health record platforms. Vulnerabilities exist for hospitalized transgender patients in the transition from the inpatient to outpatient care that require dedicated institutional efforts to address.Clinicians should learn how to engage with transgender patients, appreciate that unique anatomy or the use of gender-affirming hormones may affect the prevalence of certain disease (eg, cardiovascular disease, venous thromboembolism, and osteoporosis), and be prepared to manage specific issues, including those related to hormone therapy. Health care facilities should work toward providing inclusive systems of care that correctly identify and integrate information about transgender patients into the electronic health record, account for the unique needs of these patients within the facility, and through education and policy create a welcoming environment for their care.
Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease
Authors: Huikuan Chu, Yi Duan, Ling Yang, Bernd Schnabl
Journal: Gut (2018)

The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.
Abstract 19011: Initial Field Testing of a Cloud-based Cardiac Auscultation Information Management System in Rural Southwest Kunming Province, Peoples Republic of China
Authors: Lee A Pyles, Jihua Pan, Xiaoju Yu, Ke Liu, Jing Wang, Bistra Zheleva, Andreas Tsakistos, Weiguang Shao, Pouya Hemmati, Quan Ni
Journal: Circulation (2015)

Introduction: Auscultation (Ausc) is used around the world to screen for congenital heart disease (CHD). We describe initial field testing of a cloud-based Ausc information management system in rural China school children with limited access to cardiac care . Our goal is to develop an economical system to facilitate access to cardiac care for underserved children in low- and middle-income countries. Hypothesis: Web/cloud based distant transmission of auscultation exam can facilitate screening for congenital heart disease. Methods: A team of cardiology staff from a tertiary hospital conducted field screening for CHD) in rural school children in Yunnan Province, People’s Republic of China. Each child with a murmur with traditional Ausc underwent echo screening and digital Ausc (Thinklabs, USA). Heart sounds were collected from 5 positions (URSB, ULSB, LLSB, apex and mid-LSB), and uploaded to a server using a tablet application (HeartLink System, USA). Blinded Ausc 3-5 months later was compared with echo finding at on-site screening. Results: 8000 children were screened with standard Ausc over 4 days by a team from Kunming Medical University and First University Hospital. Heart sounds were recorded for 149 subjects. The best vibratory quality of an innocent Still murmur was heard at LLSB in 52,at mid-LSB in 51, apex in 10 and URSB/ULSB in 4. Digital Ausc found pathologic murmurs in 11 of 14 subjects with echo-diagnosed CHD. Three missed were ASD called venous hum in 2 of 3; likely related to respiratory artifact at the URSB/ULSB. Accuracy was 136/149 or 91% with 10 false positive. Positive predictive value 52% and negative predictive value 98%. The graphical phonocardiogram facilitates visual analysis of S2 splitting and the duration and timing of the cardiac murmur. Conclusions: The cloud-based digital Ausc system is able to collect, transmit, organize and display phonocardiograms for remote CHD screening and consultation. Difficulty with respiratory contamination of the signal is noted. VSD and Still murmur were successfully differentiated. The visual phonocardiographic display can aid S2 analysis for splitting. The pilot study demonstrates the potential use of this system to extend pediatric cardiology expertise to underserved rural areas around the world.
Corrigendum to “Fabrication of nanofibrous microcarriers mimicking extracellular matrix for functional microtissue formation and cartilage regeneration” [Biomaterials 171 (2018) 118–132]
Authors: Yansen Wang, Xueling Yuan, Kun Yu, Haoye Meng, Yudong Zheng, Jiang Peng, Shibi Lu, Xiaotong Liu
Journal: Biomaterials (2018)
Multiple Myeloma, Version 1.2013
Authors: Kenneth C. Anderson, Melissa Alsina, William Bensinger, J. Sybil Biermann, Adam D. Cohen, Steven Devine, Benjamin Djulbegovic, Edward A. Faber, Cristina Gasparetto, Francisco Hernandez-Illizaliturri, Carol Ann Huff, Adetola Kassim, Amrita Y. Krishnan, Michael Liedtke, Ruby Meredith, Noopur Raje, Jeffrey Schriber, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Steven P. Treon, Donna Weber, Joachim Yahalom, Furhan Yunus, Dorothy A. Shead, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2013)

These NCCN Guidelines Insights highlight the important updates/changes specific to the management of relapsed or progressive disease in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma. These changes include the addition of new regimens as options for salvage therapy and strategies to mitigate the adverse effects and risks associated with newer regimens for the treatment of multiple myeloma.