tbuckley/cabot-search huggingface dataset:
2-Deoxy-2-fluoro-D-mannose induces type II cell death in gliomas.
Authors: Leposava Antonovic, Izabela Fokt, Slawomir Szymanski, Charles Conrad, Mary Johansen, Timothy Madden, Waldemar Priebe
Journal: Cancer Research (2008)

3359  We have hypothesized that blocking glycolysis, the major energy producing pathway for fast growing, glycolytically depended cancers such as gliomas may be a powerful therapeutic strategy when used alone or in combination therapy to enhance the effects of chemotherapy in energy starved tumors. Our previous studies using the D-glucose antimetabolites 2-deoxy-D-glucose (2-DG) and 2-fluoro-deoxy-D-glucose (2-FG) have demonstrated that such an approach induces autophagic cell death in vitro and antitumor activity in vivo comparable to drugs such as temozolomide in orthotopic glioma models. In this study we investigated a novel glucose analog, 2-deoxy-2-fluoro-D-mannose (2-FM), for its ability to block glycolysis and induce autophagic cell death. Cell viability assays were carried in U87 cells treated for 72h with increasing concentrations of the 2-FM under hypoxic and normoxic conditions. The results showed 2-FM to have comparable cytotoxicity as that demonstrated by 2-DG and 2-FG in U87 cells. The IC50 values for 2-FM in U87 cells treated for 72 hrs were 3 mM in cells treated under normoxic conditions (21% O2) and 2 mM when cells were under hypoxic conditions (0.1% O2). To test the ability of the 2-FM to induce autophagic cell death we monitored the increase in acidic vesicular organelles (AVO) using acridine orange staining in U87 cells treated with 5 mM 2-FM for 72 hours. The results showed a significant increase in acridine orange staining indicating autophagic cell death under normoxia. In addition, transmission electron microscopy (TEM) studies of the cells treated with 5 mM 2-FM revealed formation of multilamellar structures, otherwise called autophagosomes, confirming Type II - autophagic cell death in cells treated with 2-FM. Our studies show that 2-FM is an equally potent inhibitor of cell proliferation and an inducer of autophagic cell death in gliomas as are 2-DG and 2-FG, and that targeting energetic metabolism of cancer cells and the autophagic survival response using inhibitors of glycolysis is a promising therapeutic approach to the treatment of cancers that are heavily dependent on glycolysis for survival.
Artificial Intelligence–Based Skin Cancer Phone Apps Unreliable
Authors: Jennifer Abbasi
Journal: JAMA (2020)

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
Rationalization as representational exchange: Scope and mechanism
Authors: Fiery Cushman
Journal: Behavioral and Brain Sciences (2020)

Abstract The commentaries suggest many important improvements to the target article. They clearly distinguish two varieties of rationalization – the traditional “motivated reasoning” model, and the proposed representational exchange model – and show that they have distinct functions and consequences. They describe how representational exchange occurs not only by post hoc rationalization but also by ex ante rationalization and other more dynamic processes. They argue that the social benefits of representational exchange are at least as important as its direct personal benefits. Finally, they construe our search for meaning, purpose, and narrative – both individually and collectively – as a variety of representational exchange. The result is a theory of rationalization as representational exchange both wider in scope and better defined in mechanism.
Radical excision versus local resection for primary rectal gastrointestinal stromal tumors. Cohort Study
Authors: Wentai Guo, Zifeng Yang, Yingqi Wei, Xiusen Qin, Chuangkun Li, Rongkang Huang, Minhui Hu, Zhantao Zeng, Huaiming Wang, Hui Wang
Journal: International Journal of Surgery (2020)
Additive manufacturing of biodegradable porous orthopaedic screw
Authors: Ramya Dhandapani, Priya Dharshini Krishnan, Allen Zennifer, Vishal Kannan, Amrutha Manigandan, Michael R. Arul, Devina Jaiswal, Anuradha Subramanian, Sangamesh Gurappa Kumbar, Swaminathan Sethuraman
Journal: Bioactive Materials (2020)

Advent of additive manufacturing in biomedical field has nurtured fabrication of complex, customizable and reproducible orthopaedic implants. Layer-by-layer deposition of biodegradable polymer employed in development of porous orthopaedic screws promises gradual dissolution and complete metabolic resorption thereby overcoming the limitations of conventional metallic screws. In the present study, screws with different pore sizes (916 × 918 μm to 254 × 146 μm) were 3D printed at 200 μm layer height by varying printing parameters such as print speed, fill density and travel speed to augment the bone ingrowth. Micro-CT analysis and scanning electron micrographs of screws with 45% fill density confirmed porous interconnections (40.1%) and optimal pore size (259 × 207 × 200 μm) without compromising the mechanical strength (24.58 ± 1.36 MPa). Due to the open pore structure, the 3D printed screws showed increased weight gain due to the deposition of calcium when incubated in simulated body fluid. Osteoblast-like cells attached on screw and infiltrated into the pores over 14 days of in vitro culture. Further, the screws also supported greater human mesenchymal stem cell adhesion, proliferation and mineralized matrix synthesis over a period of 21 days in vitro culture as compared to non-porous screws. These porous screws showed significantly increased vascularization in a rat subcutaneous implantation as compared to control screws. Porous screws produced by additive manufacturing may promote better osteointegration due to enhanced mineralization and vascularization.
Clinical Activity in a Phase 1 Study of Blu-285, a Potent, Highly-Selective Inhibitor of KIT D816V in Advanced Systemic Mastocytosis (AdvSM)
Authors: Daniel J. DeAngelo, Albert Thomas Quiery, Deepti Radia, Mark W Drummond, Jason Gotlib, William A Robinson, Elizabeth Hexner, Srdan Verstovsek, Hongliang Shi, Terri Alvarez-Diez, Oleg Schmidt-Kittler, Erica Evans, Mary Ellen Healy, Beni B. Wolf, Michael W. Deininger
Journal: Blood (2017)
Clonal Hematopoiesis: Cell of Origin, Lineage Repartition and Dynamic Evolution during Chemotherapy
Authors: Mareike Frick, Christopher Maximilian Arends, Joel Galan-Sousa, Kaja Hoyer, Willy Chan, Marten Jäger, Kenichi Yoshida, Ricarda Seemann, Daniel Nörenberg, Nils Waldhüter, Helga Fleischer-Notter, Friederike Christen, Clemens A. Schmitt, Bernd Dorken, Uwe Pelzer, Marianne Sinn, Tomasz Zemojtel, Seishi Ogawa, Sven Märdian, Adrian Schreiber, Annegret Kunitz, Ulrike Krüger, Elena Mylona, Frederik Damm
Journal: Blood (2017)
Proteomics as a reliable approach for discovery of blood-based Alzheimer’s disease biomarkers: A systematic review and meta-analysis
Authors: Siti Hajar Rehiman, Siong Meng Lim, Chin Fen Neoh, Abu Bakar Abdul Majeed, Ai-Vyrn Chin, Maw Pin Tan, Shahrul Bahyah Kamaruzzaman, Kalavathy Ramasamy
Journal: Ageing Research Reviews (2020)
A rare case of selective Igκ chain deficiency: Biologic and clinical implications
Authors: Amir A. Sadighi Akha, Renee C. Tschumper, John R. Mills, Crescent R. Isham, Elizabeth E. Witty, David S. Viswanatha, Surendra Dasari, Melissa R. Snyder, David L. Murray, Jerry A. Katzmann, Diane F. Jelinek, Maria A.V. Willrich
Journal: Journal of Allergy and Clinical Immunology (2020)
Dangers of Vitamin B<sub>6</sub>in Nursing Mothers
Authors: L B Greentree
Journal: New England Journal of Medicine (1979)

Vitamin B6 (pyridoxine hydrochloride) is contained in most prenatal and multivitamin preparations. Available research states that pyridoxine blocks lactation and inhibits the secretion of breast milk in nursing mothers by suppressing the normally elevated prolactin hormone levels encountered during puerperium. The physiologic mechanism by which pyridoxine exerts its effects is still mostly pure conjecture. According to the author, nursing mothers should take only multivitamins with essential minerals that do not include pyrodoxine. This is especially significant for areas of the world where the threat of malnutrition is present.
Mechanobiology Assays with Applications in Cardiomyocyte Biology and Cardiotoxicity
Authors: Cheavar A. Blair, Beth L. Pruitt
Journal: Advanced Healthcare Materials (2020)

Cardiomyocytes are the motor units that drive the contraction and relaxation of the heart. Traditionally, testing of drugs for cardiotoxic effects has relied on primary cardiomyocytes from animal models and focused on short-term, electrophysiological, and arrhythmogenic effects. However, primary cardiomyocytes present challenges arising from their limited viability in culture, and tissue from animal models suffers from a mismatch in their physiology to that of human heart muscle. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can address these challenges. They also offer the potential to study not only electrophysiological effects but also changes in cardiomyocyte contractile and mechanical function in response to cardiotoxic drugs. With growing recognition of the long-term cardiotoxic effects of some drugs on subcellular structure and function, there is increasing interest in using hiPSC-CMs for in vitro cardiotoxicity studies. This review provides a brief overview of techniques that can be used to quantify changes in the active force that cardiomyocytes generate and variations in their inherent stiffness in response to cardiotoxic drugs. It concludes by discussing the application of these tools in understanding how cardiotoxic drugs directly impact the mechanobiology of cardiomyocytes and how cardiomyocytes sense and respond to mechanical load at the cellular level.
Letter to the Editor: EUS‐FNA for Lymph Nodes Staging in Cholangiocarcinoma: Should It Become Standard of Care?
Authors: Alberto Larghi, Mihai Rimbaș, Francesco Ardito, Gianenrico Rizzatti, Felice Giuliante
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read the paper by Malikowski et al.(1) retrospectively assessing the value of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) staging among 157 consecutive patients with cholangiocarcinoma (CCA). A total of 301 regional lymph nodes (LFNs) were identified in 135 patients, significantly superior to computed tomography (CT)/magnetic resonance imaging (MRI) identification (86% vs. 47%; P < 0.001). EUS‐FNA was performed in 133/135 patients and identified 39 malignant regional LFNs in 27 (17%) of them who did not undergo unnecessary neoadjuvant chemoradiation ± surgery. Malignant LFNs found at surgery are one of the strongest predictors of poor outcome in CCA.(2) The present study clearly demonstrated the superiority of EUS versus CT/MRI in LFN detection, with the capability of performing EUS‐FNA that can overcome the limitation of EUS morphological assessment in predicting malignant LFN involvement.(3) Some considerations need to be done. First of all, in CCA LFN staging, it is important to distinguish regional from distant LFN sites because positivity of the latter configures a metastatic disease absolutely precluding surgery. Forty‐one percent of the malignant LFNs demonstrated by EUS‐FNA were distant metastases (periesophageal/mediastinal, celiac, aortocaval). The other 59% (gastrohepatic, periportal) were indeed true regional LFNs for which it would have been important to know the T stage to correctly define the possibility for neoadjuvant chemoradiation ± surgical intervention.(4) The influence of positive regional LFNs on surgical resectability in patients with distal CCA is lower as compared with intrahepatic and perihilar CCAs.(5) This explains the low rate of patients with distal CCA included, who had the highest proportion of malignant LFNs (33%), most likely reflecting a selection bias driven by positive imaging studies. The impact of EUS‐FNA staging reported in the study might be overestimated because 36% of the 130 patients with negative LFNs had contraindication to surgery and should not be included in the study. In addition, such vital information was not provided for patients with FNA‐positive LFNs, precluding us to fully understand the number of patients who really needed the procedure. The study clearly shows that the performance of EUS‐FNA staging in potentially resectable patients with all types of CCA is very appealing and should be fully evaluated in multicenter prospective studies to better assess the impact of the procedure before becoming the standard of care.
Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease
Authors: I-Wen Wu, Sheng-Siang Gao, Hsin-Cheng Chou, Huang-Yu Yang, Lun-Ching Chang, Yu-Lun Kuo, Michael Cong Vinh Dinh, Wen-Hung Chung, Chi-Wei Yang, Hsin-Chih Lai, Wen-Ping Hsieh, Shih-Chi Su
Journal: Theranostics (2020)

Chronic kidney disease (CKD) is a serious healthcare dilemma, associated with specific changes in gut microbiota and circulating metabolome.Yet, the functional capacity of CKD microbiome and its intricate relationship with the host metabolism at different stages of disease are less understood.Methods: Here, shotgun sequencing of fecal samples and targeted metabolomics profiling of serum bile acids, short-and medium-chain fatty acids, and uremic solutes were performed in a cohort of CKD patients with different severities and non-CKD controls.Results: We identified that levels of 13 microbial species and 6 circulating metabolites were significantly altered across early to advanced stages or only in particular stage(s).Among these, Prevotella sp.885 (decreased) was associated with urea excretion, while caproic acid (decreased) and p-cresyl sulfate (elevated) were positively and negatively correlated with the glomerular filtration rate, respectively.In addition, we identified gut microbial species linked to changes in circulating metabolites.Microbial genes related to secondary bile acid biosynthesis were differentially abundant at the early stage, while pathway modules related to lipid metabolism and lipopolysaccharide biosynthesis were enriched in the CKD microbiome at the advanced stage, suggesting that changes in microbial metabolism and host inflammation may contribute to renal health.Further, we identified metagenomic and metabolomic markers to discriminate cases of different severities from the controls, among which Bacteroides eggerthii individually was of particular value in early diagnosis.Conclusions: Our dual-omics data reveal the connections between intestinal microbes and circulating metabolites perturbed in CKD, which may be of etiological and diagnostic importance.
Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages
Authors: Yuning Lu, Gemma Basatemur, Ian C. Scott, Davide Chiarugi, Marc Clement, James Harrison, Ravin Jugdaohsingh, Xian Yu, Stephen A. Newland, Helen E. Jolin, Xuan Li, Xiao Chen, Monika Szymanska, Guttorm Haraldsen, Gaby Palmer, Padraic G. Fallon, E. Suzanne Cohen, Andrew N.J. McKenzie, Ziad Mallat
Journal: Immunity (2020)

Splenic red pulp macrophages (RPMs) contribute to erythrocyte homeostasis and are required for iron recycling. Heme induces the expression of SPIC transcription factor in monocyte-derived macrophages and promotes their differentiation into RPM precursors, pre-RPMs. However, the requirements for differentiation into mature RPMs remain unknown. Here, we have demonstrated that interleukin (IL)-33 associated with erythrocytes and co-cooperated with heme to promote the generation of mature RPMs through activation of the MyD88 adaptor protein and ERK1/2 kinases downstream of the IL-33 receptor, IL1RL1. IL-33- and IL1RL1-deficient mice showed defective iron recycling and increased splenic iron deposition. Gene expression and chromatin accessibility studies revealed a role for GATA transcription factors downstream of IL-33 signaling during the development of pre-RPMs that retained full potential to differentiate into RPMs. Thus, IL-33 instructs the development of RPMs as a response to physiological erythrocyte damage with important implications to iron recycling and iron homeostasis.
T Cell Engagement without Cytokine Storm: A Novel Bcma x CD3 Antibody Killing Myeloma Cells with Minimal Cytokine Secretion
Authors: Ben Buelow, Duy Pham, Priya Choudhry, Kevin Dang, Payal Pratap, Starlynn Clarke, Katherine Harris, Brett Jorgensen, Shelley Force Aldred, Ute Schellenberger, Nina Shah, Nathan Trinklein, Arun P. Wiita, Suhasini Iyer, Wim Van Schooten
Journal: Blood (2017)
Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline
Authors: Linda Nici, Manoj J. Mammen, Edward Charbek, Paul E. Alexander, David H. Au, Cynthia M. Boyd, Gerard J. Criner, Gavin C. Donaldson, Michael Dreher, Vincent S. Fan, Andrea S. Gershon, MeiLan K. Han, Jerry A. Krishnan, Fernando J. Martinez, Paula M. Meek, Michael Morgan, Michael I. Polkey, Milo A. Puhan, Mohsen Sadatsafavi, Don D. Sin, George R. Washko, Jadwiga A. Wedzicha, Shawn D. Aaron
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.
Covid-19: Quarantine works when introduced early alongside other measures, finds review
Authors: Elisabeth Mahase
Journal: BMJ (2020)

<h3>Abstract</h3> Cholinergic dysfunction has been implicated in the pathophysiology of psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (∼ 31 weeks of psychosis, &lt;2 defined daily dose of antipsychotics) and used Magnetic Resonance Spectroscopy (1H-MRS) and transcriptomic data to support our findings. We used a cytoarchitectonic atlas of the BF to map the nuclei and obtained measures of myelin (quantitative T1, or qT1 as myelin surrogate) and microstructure (axial diffusion; AxD). In a clinical sample (n=85; 29 healthy controls, 56 first-episode psychosis), we found significant correlations between qT1 and 1H-MRS-based dorsal anterior cingulate choline in healthy controls, while this relationship was disrupted in FEP. Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia and other psychiatric disorders such as depression.
心臓再同期療法におけるLV shuffle motionの重要性
Authors: 有田武史, 安藤献児, 曽我芳光, 山地杏平, 合屋雅彦, 岩淵成志, 横井宏佳, 安本均, 野坂秀行, 延吉正清
Journal: Circulation (2008)
Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases
Authors: Shao-Shuai Wu, Qing-Cui Li, Chang-Qing Yin, Wen Xue, Chun-Qing Song
Journal: Theranostics (2020)

CRISPR/Cas genome editing is a simple, cost effective, and highly specific technique for introducing genetic variations.In mammalian cells, CRISPR/Cas can facilitate non-homologous end joining, homologydirected repair, and single-base exchanges.Cas9/Cas12a nuclease, dCas9 transcriptional regulators, base editors, PRIME editors and RNA editing tools are widely used in basic research.Currently, a variety of CRISPR/Cas-based therapeutics are being investigated in clinical trials.Among many new findings that have advanced the field, we highlight a few recent advances that are relevant to CRISPR/Cas-based gene therapies for monogenic human genetic diseases.