tbuckley/cabot-search huggingface dataset:
Abstract 004: Microrna-22 Regulates Smooth Muscle Cell Differentiation From Stem Cells By Targeting Methyl Cpg Binding Protein 2
Authors: Hanqing Zhao, Yuan Huang, Xiaotian Yu, Guanmei Wen, Wen Wang, Shu Ye, Qingzhong Xiao
Journal: Circulation Research (2013)

Objectives: To investigate the role of microRNA-22 (miR-22) in smooth muscle cell (SMC) differentiation from stem cells and the molecular mechanism involved. Methods and Results: Mouse embryonic stem (ES) cells were seeded on collagen IV-coated flasks and cultured in the absence of Leukemia Inhibitory Factor in differentiation medium for 4 to 8 days in order to induce SMCs differentiation. We found that miR-22 was significantly up-regulated during SMC differentiation. Enforced expression of miR-22 by its mimic in differentiating ES cells significantly up-regulated expression of a panel of SMC-specific genes, while knock-down of miR-22 by its antagomiR decreased these gene expression at both RNA and protein levels. Furthermore, we found over-expression and knockdown of miR-22 up-regulated and down-regulated SMC transcription factor SRF and its co-activator myocardin in a similar manner, respectively, and miR-22 overexpression in stem cells promoted SMC differentiation in vivo . Transcription repressor methyl CpG binding protein 2 (MECP2) was predicted as one of the top targets of miR-22 by using several computational miRNA target prediction tools. Interestingly, the gene expression levels of MECP2 were significantly decreased during SMC differentiation in a time dependent manner. Moreover, MECP2 was dramatically decreased in miR-22 overexpressing cells, but significantly increased when miR-22 was knockdown in the differentiating stem cells. Importantly, luciferase assay showed miR-22 substantially inhibited wild type MECP2-3’-UTR-luciferase activity in differentiating ES cells, but not mutant MECP2-3’-UTR-luciferease reporter. In addition, modulation of MECP2 expression levels affect multiple SMC-specific marker gene expression in differentiated ES cells by conducting gain-of-function experiments using MECP2 expression plasmid. Finally, we tested the expression of miR-22 in mouse femoral artery denudation injury model and found that miR-22 was significantly down-regulated in the wire injury-induced neointimal formation as early as day 3 post-injury. Conculsion: Using genomic and functional studies, we have discovered miR-22 controls SMC differentiation from stem cells via modulating MECP2 expression and function.
Symptoms, cancer‐related distress, and overall distress may contribute to racial disparities in the outcomes of patients with early‐stage breast cancer
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2017)

Key Points Only 60% of AA women with early‐stage BC received at least 85% of the prescribed adjuvant chemotherapy within the prescribed timeframe. The number of symptoms and symptom distress were related to the ability to receive timely, full‐dose adjuvant chemotherapy. These findings provide an actionable area in which to potentially decrease cancer treatment disparities.
Complex and Dynamic Chromosomal Rearrangements in a Family With Seemingly Non-Mendelian Inheritance of Dopa-Responsive Dystonia
Authors: Katja Lohmann, Claire Redin, Holger Tönnies, Susan B. Bressman, Jose Ignacio Martin Subero, Karin Wiegers, Frauke Hinrichs, Yorck Hellenbroich, Aleksandar Rakovic, Deborah Raymond, Laurie J. Ozelius, Eberhard Schwinger, Reiner Siebert, Michael E. Talkowski, Rachel Saunders-Pullman, Christine Klein
Journal: JAMA Neurology (2017)

Chromosomal rearrangements are increasingly recognized to underlie neurologic disorders and are often accompanied by additional clinical signs beyond the gene-specific phenotypic spectrum.To elucidate the causal genetic variant in a large US family with co-occurrence of dopa-responsive dystonia as well as skeletal and eye abnormalities (ie, ptosis, myopia, and retina detachment).We examined 10 members of a family, including 5 patients with dopa-responsive dystonia and skeletal and/or eye abnormalities, from a US tertiary referral center for neurological diseases using multiple conventional molecular methods, including fluorescence in situ hybridization and array comparative genomic hybridization as well as large-insert whole-genome sequencing to survey multiple classes of genomic variations. Of note, there was a seemingly implausible transmission pattern in this family due to a mutation-negative obligate mutation carrier.Genetic diagnosis in affected family members and insight into the formation of large deletions.Four members were diagnosed with definite and 1 with probable dopa-responsive dystonia. All 5 affected individuals carried a large heterozygous deletion encompassing all 6 exons of GCH1. Additionally, all mutation carriers had congenital ptosis requiring surgery, 4 had myopia, 2 had retinal detachment, and 2 showed skeletal abnormalities of the hands, ie, polydactyly or syndactyly or missing a hand digit. Two individuals were reported to be free of any disease. Analyses revealed complex chromosomal rearrangements on chromosome 14q21-22 in unaffected individuals that triggered the expansion to a larger deletion segregating with affection status. The expansion occurred recurrently, explaining the seemingly non-mendelian inheritance pattern. These rearrangements included a deletion of GCH1, which likely contributes to the dopa-responsive dystonia, as well as a deletion of BMP4 as a potential cause of digital and eye abnormalities.Our findings alert neurologists to the importance of clinical red flags, ie, unexpected co-occurrence of clinical features that may point to the presence of chromosomal rearrangements as the primary disease cause. The clinical management and diagnostics of such patients requires an interdisciplinary approach in modern clinical-diagnostic care.
Can We Improve the Predictive Value of Interim PET/CT Using a New Prognostic Model for Advanced Hodgkin Lymphoma?
Authors: Eldad J. Dann, Osnat Bairey, Rachel Bar-Shalom, Tanya Mashiach, Elinor Barzilai, Abraham Korenberg, Luiza Akria, Tamar Tadmor, Kalman Filanovsky, Uri Abadi, Olga Kagna, Rosa Ruchlemer, Neta Goldschmidt, Netanel A. Horowitz, David Lavie, Dina Ben-Yehuda, Ofer Shpilberg, Ora B. Paltiel
Journal: Blood (2016)
Preparation courses for medical school are isolating and demotivating
Authors: Angelica Sharma
Journal: BMJ (2017)

McCartney highlights the unfairness of “preparation courses” set up by private companies for applying to medical school.1 I felt pressured into attending such courses and felt uncompetitive when realising they were out of my price bracket or a long train journey away. My peers were constantly nervous, saying “There goes my last chance at success” …
Long-lasting tuberculous pleurisy
Authors: Luca Ampollini, Antonio Bobbio, Luigi Ventura, Claudia Schianchi, Paolo Carbognani, Michele Rusca
Journal: European Respiratory Journal (2017)

We read with great interest the paper by Petruccioli et al . [1] where the authors describe new prognostic tests and different approaches that can predict the progression from latent to active tuberculosis (TB). We have taken the opportunity to comment on this paper to describe a recent case of recurrent tuberculous infection in a patient with a long-lasting history of tuberculous pleurisy and secondary residual pleural thickening. Tuberculous pleurisy and subsequent pleural thickening could be associated with recurrent tuberculous infection <http://ow.ly/BLGK30aJjvI> We would like to thank Petruccioli, Elisa (National Institute for Infectious Diseases “L. Spallanzani”, Rome, Italy) and co-workers for their comprehensive work on different tools for predicting the development of active TB from latent TB infection.
Parents of child with rare genetic disorder lose life support appeal
Authors: Clare Dyer
Journal: BMJ (2017)

The parents of a baby with a rare genetic disorder have lost their appeal against a High Court ruling that it would be against the child’s best interests to go to the US for experimental treatment.

Chris Gard and Connie Yates raised £1.3m (€1.5m; $1.7m) through crowdfunding to take their nine month old son Charlie, who has mitochondrial DNA depletion …
EPND-08. EPIGENETIC H3K27ME3 DEREGULATION IN PEDIATRIC POSTERIOR FOSSA EPENDYMOMAS
Authors: Sriram Venneti, Jill Bayliss, Piyali Mukherjee, Chao Lu, Siddhant Jain, Chan Chung, Pooja Panwalkar, Daniel Martinez, Benjamin Sabari, Ashley Margol, Melike Pekmezci, Marcin Cieslik, Benita Tamrazi, Benjamin Garcia, Mariarita Santi, Peter Lewis, Cynthia Hawkins, David Allis, Arul Chinnaiyan, Alexander Judkins
Journal: Neuro-Oncology (2017)

Ependymomas in children occur most commonly in the posterior fossa of the brain and cause significant morbidity and mortality. The pathogenesis of these tumors remains obscure as recent whole genome and whole exome sequencing efforts have not yielded recurrent genetic mutations. These tumors exhibit abnormal CpG island methylation, suggesting that epigenetic alterations may be a significant driver. To gain insights into the epigenetics of childhood ependymomas, we performed mass spectroscopy for histone modifications to discover that H3K27 trimethylation was globally reduced in these tumors. Despite global reduction in H3K27me3, ChIP-sequencing for H3K27me3 revealed genomic enrichment at several loci important for neurodevelopment. In a cohort of 195 childhood posterior fossa ependymoma samples, reduction in H3K27me3 was associated with worse prognosis (p<0.0001). Comparison of DNA methylation and genome-wide H3K27me3 enrichment from both H3K27M mutant diffuse intrinsic pontine gliomas and childhood ependymomas patient samples showed many similarities and pointed to factors that regulate radial glial (neuronal stem cells) development. Human radial glial cells during development exhibit low H3K27me3. Ependymomas with reduced H3K27me3 corresponded to younger children (p<0.0001), arose mainly from the roof of the forth ventricle, exhibited increased evidence of radiologic and histopathologic invasion and exhibited clinical features consistent with previously described PFA subgroup of ependymomas. Together these data suggest that the epigenetics of the developing posterior fossa are closely related to the pathogenesis of childhood brain tumors and have clinical implications for biomarker development and to inform epigenetic approaches to treat PF ependymomas.
Adrenergic Receptors in Individual Ventricular Myocytes
Authors: Bat-Erdene Myagmar, James M. Flynn, Patrick M. Cowley, Philip M. Swigart, Megan D. Montgomery, Kevin Thai, Divya Nair, Rumita Gupta, David X. Deng, Chihiro Hosoda, Simon Melov, Anthony J. Baker, Paul C. Simpson
Journal: Circulation Research (2017)

Rationale: It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), β1, β2, β3, α1A, and α1B. The β1 and β2 are thought to be the dominant myocyte ARs. Objective: Quantify the 5 cardiac ARs in individual ventricular myocytes. Methods and Results: We studied ventricular myocytes from wild-type mice, mice with α1A and α1B knockin reporters, and β1 and β2 knockout mice. Using individual isolated cells, we measured knockin reporters, mRNAs, signaling (phosphorylation of extracellular signal–regulated kinase and phospholamban), and contraction. We found that the β1 and α1B were present in all myocytes. The α1A was present in 60%, with high levels in 20%. The β2 and β3 were detected in only ≈5% of myocytes, mostly in different cells. In intact heart, 30% of total β-ARs were β2 and 20% were β3, both mainly in nonmyocytes. Conclusion: The dominant ventricular myocyte ARs present in all cells are the β1 and α1B. The β2 and β3 are mostly absent in myocytes but are abundant in nonmyocytes. The α1A is in just over half of cells, but only 20% have high levels. Four distinct myocyte AR phenotypes are defined: 30% of cells with β1 and α1B only; 60% that also have the α1A; and 5% each that also have the β2 or β3. The results raise cautions in experimental design, such as receptor overexpression in myocytes that do not express the AR normally. The data suggest new paradigms in cardiac adrenergic signaling mechanisms.
Characterization of the CATS Protein Which Interacts with the Leukemogenic Fusion Protein CALM/AF10 Using Mono-Clonal Antibodies and Fluroescent Protein Tags.
Authors: Leticia Fröhlich Archangelo, Alexandre Krause, Michael Hölzel, Elisabeth Kremmer, Aniruddha Deshpande, Christian Buske, Stefan K. Bohlander
Journal: Blood (2005)
THE HYGIENE OF CLOTHING.
Journal: JAMA (1898)

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
Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin
Authors: Aaron Seo, Miri Ben-Harosh, Mehtap Sirin, Jerry Stein, Orly Dgany, Joseph Kaplelushnik, Manfred Hoenig, Ulrich Pannicke, Myriam Lorenz, Klaus Schwarz, Clemens Stockklausner, Tom Walsh, Suleyman Gulsuner, Ming K. Lee, Anoop Sendamarai, Marilyn Sanchez-Bonilla, Mary-Claire King, Holger Cario, Andreas E. Kulozik, Klaus-Michael Debatin, Ansgar Schulz, Hannah Tamary, Akiko Shimamura
Journal: Blood (2017)
NHS must be an election priority, says BMA chair
Authors: Abi Rimmer
Journal: BMJ (2017)

The NHS needs the unrelenting focus of politicians and must not be sidelined by Brexit as a priority in the upcoming general election, Mark Porter, the BMA’s chair of council, has said.

In his introduction to the BMA’s manifesto for the general election on 8 June Porter said that it would be all too easy for the election to become focused on the UK leaving the European Union “at precisely the time when the health service needs the unrelenting focus of politicians from all parties.”1

He said that the NHS was at breaking point, adding, “Despite …
Bone Marrow Derived Mesenchymal Stromal Cells Reduce the Incidence of Chronic Graft-Versus-Host Disease after Allogenetic Hematopoietic Stem Cell Transplantation
Authors: Ke Zhao, Zhiping Fan, Fen Huang, Shunqing Wang, Peng Xiang, Qi Zhang, Qifa Liu
Journal: Blood (2016)
Cancer Metastasis: A Reappraisal of Its Underlying Mechanisms and Their Relevance to Treatment
Authors: Nicolo Riggi, Michel Aguet, Ivan Stamenkovic
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

Metastases are responsible for the vast majority of cancer-related deaths, but, despite intense efforts to understand their underlying mechanisms with the goal of uncovering effective therapeutic targets, treatment of metastatic cancer has progressed minimally. In this review, we examine the biological programs currently proposed to be key drivers of metastasis. On the basis of evidence from a growing body of research, we discuss to what extent the cellular and molecular mechanisms that are suggested to underlie cancer cell dissemination are specific to the metastatic process, as opposed to representing natural primary tumor progression. Our review highlights the contrast between the abundance of insight gained into the events that constitute the metastatic cascade and the paucity of therapeutic options.
Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex
Authors: Jorge Sepulcre, Michel J. Grothe, Mert Sabuncu, Jasmeer Chhatwal, Aaron P. Schultz, Bernard Hanseeuw, Georges El Fakhri, Reisa Sperling, Keith A. Johnson
Journal: JAMA Neurology (2017)

Abnormal accumulation of tau and amyloid-β (Aβ) proteins in the human brain are 2 pathologic hallmarks of Alzheimer disease (AD). Because pathologic processes begin decades before the onset of the clinical manifestations, the study of the cortical distribution of early-stage pathologic alterations is critical in understanding the underpinnings of the disease.To identify the in vivo brain spatial distributions of tau and Aβ deposits in a sample of cognitively normal participants in the Harvard Aging Brain Study, determine spatial patterns of pathologic alterations, and provide means for improved individual in vivo staging.Eighty-eight individuals from the general community underwent flortaucipir 18 T807 (18F-T807) and carbon 11-labeled Pittsburgh Compound B (11C-PiB) positron emission tomographic (PET) imaging. A voxel-level hierarchical clustering approach was used to obtain the main clustering partitions corresponding to the cortical distribution maps of 18F-T807 and 11C-PiB. Hierarchical relationships between areas of distinctive pathologic deposits were then studied. Using cerebellar gray reference, 18F-T807 data were expressed as standardized uptake value ratio, and 11C-PiB were given as distribution volume ratio.Main in vivo and hierarchically organized tau and Aβ deposits in the elderly brain.Of the 88 study participants, 39 (44%) were men, with a mean (SD) age of 76.2 (6.2) years. The tau and Aβ maps both displayed optimal cortical partitions at 4 clusters. The tau deposits were grouped in the temporal lobe, distributed in heteromodal areas, medial and visual regions, and primary somatomotor cortex; the Aβ deposits were clustered in the heteromodal areas and rather patchy in distributed regions involving the primary cortices, medial structures, and temporal areas. Moreover, tau deposits in the temporal lobe and distributed heteromodal areas were tightly nested.Tau and Aβ deposits in the elderly brain generally display well-defined hierarchical cortical relationships as well as overlaps between the principal clusters of both pathologic alterations in the heteromodal association regions. These findings represent systematic, large-scale mechanisms of early AD pathology.
Predicting protracted recovery in professional rugby union: what can the symptoms, signs and modifiers of concussion tell us?
Authors: Cross Matthew, Keith Stokes, Simon Kemp, Andy Smith, Grant Trewartha
Journal: British Journal of Sports Medicine (2017)

Objective To investigate the association between the signs, symptoms and modifiers of concussion and protracted recovery in professional Rugby Union players. Design Prospective cohort. Setting The English Premiership (the highest level of competition in England). Participants 810 professional Rugby Union players over two seasons (2012/13 and 2013/14). 150 players reported 181 concussions for which 100 provided data for this analysis (80 concussions had insufficient follow up and 1 player left the study). Independent variables Symptoms were grouped into 4 domains (head, cognitive, sleep and neuropsychological) previously demonstrated to have adequate internal consistency (Pardini et al., Brit J Sports Med: 38, 661–662, 2004). Symptom burden and standardised assessment of concussion (SAC) scores alongside signs and modifiers (amnesia, loss of consciousness, previous concussion history and balance error score) were also reported. Dependent Variable Time (days) to return to play (RTP). Protracted recovery was defined as &gt;14 days. Main results Eighteen percent of players did not RTP within 14 days. Higher symptom burden (OR 1.17, 95% CI 1.01–1.31) and higher balance error scores (OR 1.33, 95% CI 1.06–1.66) were associated with protracted recovery. A higher number of self-reported ‘head cluster’ symptoms were associated with a shorter (&lt;14 days) recovery time (OR 0.90, 95% CI: 0.82–0.98). Conclusions Clinicians should pay particular attention to higher symptom burden and balance error scores as part of a multimodal assessment to aid early identification of protracted recovery. The association between balance and protracted recovery suggests that targeted rehabilitation programs to improve the vestibular system warrant further investigation. Competing interests Dr. Matthew Cross – Employed by the Rugby Football Union who part funded the PhD (stipend and fees) that this study was part of Dr. Keith Stokes – Receives research funding from the Rugby Football Union Dr. Simon Kemp – Employed by the Rugby Football Union Dr. Andy Smith – Employed by Premiership Rugby who part funded the PhD (stipend and fees) that this study was part of Dr. Grant Trewartha – Receives research funding from the Rugby Football Union
Erratum: Cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor therapy in older patients with myocardial infarction (Annals of Internal Medicine (2000) 132 (780-787))
Authors: D. A. Ganz, K. M. Kuntz, G. A. Jacobson, J. Avorn
Journal: Annals of Internal Medicine (2002)
Abstract P206: Automated Imaging Reveals a Switch Between Reversible and Irreversible Cardiac Myocyte Hypertrophy
Authors: Karen A Ryall, Jeffrey J Saucerman
Journal: Circulation Research (2011)

Cardiac hypertrophy increases risk for heart failure, arrhythmia, and sudden death. Little is known about the specific signaling pathways that distinguish reversible forms of hypertrophy from irreversible forms which lead to heart failure. This project utilizes a novel high-throughput cell phenotype imaging and analysis protocol to study the reversibility of cardiac myocyte hypertrophy in a scalable cell culture model. Primary cardiac myocytes were transfected with GFP plasmid driven under a cardiac specific troponin T promoter. Five by five mosaic images (∼100 cells) within each well of a 96-well plate were recorded with an automated XYZ stage and focus. Post-processing algorithms automatically background corrected, segmented cell edges, quantified cell phenotypes, and tracked cells between measurements. This platform therefore has the ability to track changes in area and shape of hundreds of individual cells over a time period of about a week. Cell shape changes after washout of a dose response to the hypertrophic agonist phenylephrine (PE) showed that hypertrophy was reversible at low but not high levels of alpha-adrenergic signaling: a cellular “toggle switch”. Specialized alpha-adrenergic receptor (αAR) antagonists were used to study a potential mechanism for this biphasic response. Prazosin, an αAR antagonist that could act at the sarcolemma and also be transported inside the cell, reversed PE-induced hypertrophy. In contrast, CGP-12177a, an αAR antagonist that acts at the sarcolemma, did not reverse PE-induced hypertrophy. These experimental results and a computational model support the hypothesis that cellular uptake of PE and activity at nuclear alpha-adrenergic receptors may explain the biphasic response in the reversibility of PE-induced hypertrophy.