tbuckley/cabot-search huggingface dataset:
Three-dimensional architecture of nephrons in the normal and cystic kidney
Authors: Thomas Blanc, Nicolas Goudin, Mohamad Zaidan, Meriem Garfa Traore, Frank Bienaime, Lisa Turinsky, Serge Garbay, Clément Nguyen, Martine Burtin, Gérard Friedlander, Fabiola Terzi, Marco Pontoglio
Journal: Kidney International (2020)

Kidney function is crucially dependent on the complex three-dimensional structure of nephrons. Any distortion of their shape may lead to kidney dysfunction. Traditional histological methods present major limitations for three-dimensional tissue reconstruction. Here, we combined tissue clearing, multi-photon microscopy and digital tracing for the reconstruction of single nephrons under physiological and pathological conditions. Sets of nephrons differing in location, shape and size according to their function were identified. Interestingly, nephrons tend to lie in planes. When this technique was applied to a model of cystic kidney disease, cysts were found to develop only in specific nephron segments. Along the same segment, cysts are contiguous within normal non-dilated tubules. Moreover, the shapes of cysts varied according to the nephron segment. Thus, our findings provide a valuable strategy for visualizing the complex structure of kidneys at the single nephron level and, more importantly, provide a basis for understanding pathological processes such as cystogenesis.
Safety, Tolerability and Efficacy of Cael-101 in AL Amyloidosis Patients Treated on a Phase 2, Open-Label, Dose Selection Study to Evaluate the Safety and Tolerability of Cael-101 in Patients with AL Amyloidosis
Authors: Jack Khouri, Faiz Anwer, Christy J. Samaras, Alex V. Mejia Garcia, Omer N. Koc, Beth M. Faiman, Kimberly Hamilton, Saveta Mathur, Cynthia Scott, Kathleen Stefunek, Josephine Sgobbo, Sherry Fada, Brittany Lewis, Kelly Shepherd, Naqib Ahmad, Madeleine Knebusch, Susan B. Sobolov, Janet Jobes, Eileen Daniel, Michael Spector, Jason Valent
Journal: Blood (2020)
The Copy Number Landscape of Relapsed and Refractory Diffuse Large B-Cell Lymphoma
Authors: Christopher Rushton, Miguel Alcaide, Matthew Cheung, Neil R Michaud, Scott Daigle, Ryan N Rys, Sarah E Arthur, Marquisa Zrymiak, Jordan Davidson, Kevin R Bushell, Stephen Yu, Michael D. Jain, Lois E. Shepherd, Marco A. Marra, John Kuruvilla, Michael Crump, Koren Kathleen Mann, Sarit E Assouline, Joseph M. Connors, Christian Steidl, Nathalie A Johnson, David W. Scott, Ryan D Morin
Journal: Blood (2020)
Financial Consequences of Drug Benefit Plans—Reply
Authors: Geoffrey F. Joyce, Dana P. Goldman
Journal: JAMA (2003)

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
ZNF410 Represses Fetal Globin By Devoted Control of CHD4/NuRD
Authors: Divya S Vinjamur, Qiuming Yao, Mitchel A. Cole, Connor McGuckin, Chunyan Ren, Jing Zeng, Mir Hossain, Luca Pinello, Daniel E Bauer
Journal: Blood (2020)
Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer
Authors: Shuang Zhang, Sonia Iyer, Hao Ran, Igor Dolgalev, Shengqing Gu, Wei Wei, Connor J.R. Foster, Cynthia A. Loomis, Narciso Olvera, Fanny Dao, Douglas A. Levine, Robert A. Weinberg, Benjamin G. Neel
Journal: Cancer Discovery (2020)

Abstract The paucity of genetically informed, immunocompetent tumor models impedes evaluation of conventional, targeted, and immune therapies. By engineering mouse fallopian tube epithelial organoids using lentiviral gene transduction and/or CRISPR/Cas9 mutagenesis, we generated multiple high-grade serous tubo-ovarian cancer (HGSC) models exhibiting mutational combinations seen in patients with HGSC. Detailed analysis of homologous recombination (HR)–proficient (Trp53−/−;Ccne1OE;Akt2OE;KrasOE), HR-deficient (Trp53−/−;Brca1−/−;MycOE), and unclassified (Trp53−/−;Pten−/−;Nf1−/−) organoids revealed differences in in vitro properties (proliferation, differentiation, and “secretome”), copy-number aberrations, and tumorigenicity. Tumorigenic organoids had variable sensitivity to HGSC chemotherapeutics, and evoked distinct immune microenvironments that could be modulated by neutralizing organoid-produced chemokines/cytokines. These findings enabled development of a chemotherapy/immunotherapy regimen that yielded durable, T cell–dependent responses in Trp53−/−;Ccne1OE;Akt2OE;Kras HGSC; in contrast, Trp53−/−;Pten−/−;Nf1−/− tumors failed to respond. Mouse and human HGSC models showed genotype-dependent similarities in chemosensitivity, secretome, and immune microenvironment. Genotype-informed, syngeneic organoid models could provide a platform for the rapid evaluation of tumor biology and therapeutics. Significance: The lack of genetically informed, diverse, immunocompetent models poses a major barrier to therapeutic development for many malignancies. Using engineered fallopian tube organoids to study the cell-autonomous and cell-nonautonomous effects of specific combinations of mutations found in HGSC, we suggest an effective combination treatment for the currently intractable CCNE1-amplified subgroup. This article is highlighted in the In This Issue feature, p. 211
Real-World Characteristics of Patients with Classical Hodgkin Lymphoma Receiving Frontline Brentuximab Vedotin with Chemotherapy: A Retrospective Analysis with Propensity Score Matching
Authors: Tycel J. Phillips, Kristina Yu-Isenberg, Nicholas Liu, Andy Surinach, Carlos Flores, Julie Lisano, Michelle A. Fanale, John M. Burke
Journal: Blood (2020)
AB0125 Rapid and complete remission in treatment resistant ankylosing spondylitis with etanercept – a better drug for refractory as than for refractory ra?
Authors: HR Barthel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Two treatment-resistant, HLA-B27 positive patients with ankylosing spondylitis (AS-pat.1&amp;2) are described in whom etanercept led to a rapid profound improvement in symptoms as well as normalisation of CRP. <h3>Objectives</h3> <h3>Methods</h3> AS-pat.1 is a 37 y.o. male with highly active AS with generalised stiffness and pain. Subcutaneous (s.c.) weekly MTX over one year in addition to the prior regimen of indomethacin 150 mg/d led to only moderate improvement in symptoms and reduction of CRP from 8 mg/dl to 4 mg/dl. A trial of I. V. pamidronate failed. Etanercept 25 mg s.c. twice/wk was added to MTX. He reported an immediate dramatic improvement of symptoms and stopped indomethacin the day after the first injection. CRP normalised. MTX was stopped after 1 month. He describes a "new life" and that he now plays badminton with his children which he was unable to do before. AS-pat.2 is a 66 y.o. male with longstanding AS and a history of recurrent iritis. He suffered from morning stiffness and from repeated flarings of varying peripheral joints despite corticosteroid joint injections, indomethacin up to 150 mg/d and a 2 1/2 months trial of MTX 15 mg weekly. Etanercept 25 mg s.c. twice weekly led to rapid and dramatic improvement of pain and stiffness within 2 days, such that the patient did not continue MTX. CRP of 3 mg/dl normalised. No new flare of arthritis or iritis has occurred. <h3>Results</h3> Both AS-pat. results (follow up of 8 months) appear particularly remarkable since none of the 9 RA pat. (disease duration more than 4 years, more than 3 failed DMARDs) treated with etanercept-DMARD combination in the same practice (community based, single practitioner rheumatology) in a one year period (9/99–8/2000) had a similar response. Only 4 stayed on etanercept, 3 withdrew due to lack of efficacy, 2 because of side effects. <h3>Conclusion</h3> The herein described profound improvement of so far treatment resistant AS with etanercept and its superior efficacy for AS compared to RA warrants further confirmation. Etanercept's only moderate benefit for RA in this setting might be explained by a selection of aggressive cases not having responded to prior DMARD combination therapy.
Abstract 296: The MicroRNA <i>-134-5p</i> Induces Calcium Deposition by Inhibiting Hdac5 in Vascular Smooth Muscle Cells
Authors: Nakwon Choe, SERA SHIN, Hosouk Joung, Juhee Ryu, Young-Kook Kim, Youngkeun Ahn, Duk-hwa Kwon, Hyun Kook
Journal: Circulation Research (2020)

Calcium deposition in vascular smooth muscle cells (VSMCs) is a form of ectopic ossification in blood vessels. It can result in rigidity of the vasculature and an increase in cardiac events. Here, we report that the microRNA-134-5p ( miR-134-5p) potentiates inorganic phosphate (Pi)-induced calcium deposition in VSMCs by inhibiting histone deacetylase 5 (HDAC5). Using miRNA microarray analysis of Pi-treated rat VSMCs, we first selected miR-134-5p for further evaluation. Quantitative RT-PCR confirmed that miR-134-5p was increased in Pi-treated A10 cells, a rat VSMC line. Transfection of miR-134-5p mimic potentiated the Pi-induced increase in calcium contents. miR-134-5p increased the amounts of bone runt-related transcription factor 2 (RUNX2) protein and bone morphogenic protein (BMP2) mRNA in the presence of Pi but decreased the expression of osteoprotegerin (OPG). Bioinformatic analysis showed that the HDAC5 5’UTR was one of the targets of miR-134-5p . Hdac5 expression was downregulated by miR-134-5p mimic in an Hdac5 5’UTR-dependent manner. Overexpression of Hdac5 mitigated the calcium deposition induced by miR-134-5p . Our results suggest that a Pi-induced increase of miR-134-5p may cause vascular calcification through repression of HDAC5.
CoupledCARTM Technology for Treating Thyroid Cancer
Authors: Xingchen Liu, Lei Xiao, Keshu Zhou, Yu Liu, Yong Huang, Chengfei Pu, Zhiyuan Cao, Ruihong Zhu, Haiyang Tang, Zhipeng Huang, Hang Yang, Xi Huang, Yongping Song, Renbin Liu, Zhao Wu
Journal: Blood (2020)
Bendamustine Plus Rituximab for the Treatment of Waldenström Macroglobulinaemia: Patient Outcomes and Impact of Bendamustine Dosing
Authors: Suzanne O Arulogun, Duncan Brian, Harshita Goradia, Aaron Cooney, Tobias Menne, Dipti Talaulikar, Aideen Therese O'Neill, Josephine M.I Vos, Guy Pratt, Deborah Turner, Kirsty Marshall, Kate Manos, Claire Anderson, Maria Gavriatopoulou, Charalampia Kyriakou, Monique C. Minnema, Dima El-Sharkawi, Marie José Kersten, RayMun Koo, Helen McCarthy, Mark Bishton, George Follows, Ashutosh D. Wechalekar, Shirley D'Sa
Journal: Blood (2020)
An Insight into the Impact of Hemophilia a on Daily Life According to Disease Severity: A Preliminary Analysis of the CHESS II Study
Authors: Declan Noone, Francis Nissen, Tao Xu, Tom Burke, Sohaib Asghar, Harpal Dhillon, Martynas Aizenas, Oliver Meier, Jamie O'Hara, Kate Khair
Journal: Blood (2020)
Abstract IA15: Inflammatory memory and tumorigenesis
Authors: Shruti Naik
Journal: Cancer Research (2020)

Abstract Our body’s epithelia are barriers that interface with the terrestrial environment and routinely experience inflammation. Although a vast majority of these inflammatory reactions resolve, they imprint the tissue with a memory. Cells of the immune system are traditionally thought to be the bearers of this memory, allowing them to react faster to subsequent inflammatory pressures. Yet, barrier tissues are composites of epithelial, mesenchymal, nervous, vascular, and immunological networks working in unison to sustain optimal function. I discuss the enduring impact of inflammatory exposures on the skin epithelia and in particular on their long-lived stem cells, and the implications for such inflammatory training in tumor predisposition. Citation Format: Shruti Naik. Inflammatory memory and tumorigenesis [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA15.
Abstract B19: Suppression of CD8+ T-cell functions by melanoma cell-derived exosomes captured from plasma of patients with melanoma
Authors: Priyanka Sharma, Brenda Diergaarde, Soldano Ferrone, John M Kirkwood, Theresa L. Whiteside
Journal: Cancer Research (2020)

Abstract Exosomes, virus-sized (30-150nm) vesicles, derived from the endocytic compartment of parent cells, are produced by all cells and are present in all body fluids. Melanoma patients’ plasma contains exosomes produced by normal and malignant cells. To study the impact of melanoma cell-derived exosomes (MTEX) on human immune cells and melanoma progression, we isolated MTEX from total exosomes in plasma by immune capture with anti-CSPG-4 mAbs on beads. 19 proteins carried by MTEX and by non-MTEX of 12 patients with metastatic melanoma were quantified by on-bead flowcytometry. Immunoregulatory functions of these exosomes were measured in co-incubation assays with human immune cell subsets. Plasma exosomes of 6 normal donors served as controls. Melanoma-associated antigens (MAA) were present on MTEX only. MTEX carried more inhibitory ligands than non-MTEX (FasL, p&amp;lt;0.007; TRAIL, p&amp;lt;0.02), inhibited CD69 expression (p&amp;lt;0.002) on CD8+ T cells, suppressed T-cell proliferation (p&amp;lt;0.0005), and induced apoptosis of CD8+ T cells (p&amp;lt; 0.0005). MTEX-mediated suppression accounted for suppressive activities of total plasma exosomes. Although non-MTEX were enriched in immunostimulatory proteins (p&amp;lt;0.002), they induced greater suppression of NKG2D on NK cells than MTEX (p&amp;lt;0.001). This is the first study to show that MTEX, a subset of circulating exosomes derived from melanoma cells, are largely responsible for immuno-suppressive effects that potentially translate into systemic immune suppression and tumor promotion in melanoma patients. Citation Format: Priyanka Sharma, Brenda Diergaarde, Soldano Ferrone, John M Kirkwood, Theresa L. Whiteside. Suppression of CD8+ T-cell functions by melanoma cell-derived exosomes captured from plasma of patients with melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B19.
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Authors: Zonghua Li, Francis Shue, Na Zhao, Mitsuru Shinohara, Guojun Bu
Journal: Molecular Neurodegeneration (2020)

Abstract Investigations of apolipoprotein E ( APOE ) gene, the major genetic risk modifier for Alzheimer’s disease (AD), have yielded significant insights into the pathogenic mechanism. Among the three common coding variants, APOE*ε4 increases, whereas APOE*ε2 decreases the risk of late-onset AD compared with APOE*ε3 . Despite increased understanding of the detrimental effect of APOE*ε4 , it remains unclear how APOE*ε2 confers protection against AD. Accumulating evidence suggests that APOE*ε2 protects against AD through both amyloid-β (Aβ)-dependent and independent mechanisms. In addition, APOE*ε2 has been identified as a longevity gene, suggesting a systemic effect of APOE*ε2 on the aging process. However, APOE*ε2 is not entirely benign; APOE*ε2 carriers exhibit increased risk of certain cerebrovascular diseases and neurological disorders. Here, we review evidence from both human and animal studies demonstrating the protective effect of APOE*ε2 against AD and propose a working model depicting potential underlying mechanisms. Finally, we discuss potential therapeutic strategies designed to leverage the protective effect of APOE2 to treat AD.
Activity of Venetoclax-Based Therapy in CMML and CMML with Blast Transformation
Authors: Danielle Hammond, Courtney D. DiNardo, Marina Konopleva, Gautam Borthakur, Jorge M. Ramos Perez, Veronica A Guerra, Rashmi Kanagal-Shamanna, Shilpa Paul, Kiran Naqvi, Koji Sasaki, Elias Jabbour, Naveen Pemmaraju, Tapan M. Kadia, Farhad Ravandi, Naval Daver, Zeev E. Estrov, Sherry A. Pierce, Hagop M. Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo
Journal: Blood (2020)
Large‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis
Authors: Chiara Bellocchi, Jun Ying, Ellen A. Goldmuntz, Lynette Keyes‐Elstein, John Varga, Monique E. Hinchcliff, Marka A. Lyons, Peter McSweeney, Daniel E. Furst, Richard Nash, Leslie J. Crofford, Beverly Welch, Jonathan G. Goldin, Ashley Pinckney, Maureen D. Mayes, Keith M. Sullivan, Shervin Assassi
Journal: Arthritis & Rheumatology (2020)

To provide a large-scale assessment of serum protein dysregulation in diffuse cutaneous systemic sclerosis (dcSSc) and to investigate serum protein correlates of SSc fibrotic features.We investigated serum protein profiles of 66 participants with dcSSc at baseline who were enrolled in the Scleroderma: Cyclophosphamide or Transplant Trial and 66 age- and sex-matched healthy control subjects. A panel of 230 proteins, including several cytokines and chemokines, was investigated. Whole blood gene expression profiling in concomitantly collected samples was performed.Among the participants with dcSSc, the mean disease duration was 2.3 years. All had interstitial lung disease (ILD), and none were being treated with immunosuppressive agents at baseline. Ninety proteins were differentially expressed in participants with dcSSc compared to healthy control subjects. Similar to previous global skin transcript results, hepatic fibrosis, granulocyte and agranulocyte adhesion, and diapedesis were the top overrepresented pathways. Eighteen proteins correlated with the modified Rodnan skin thickness score (MRSS). Soluble epidermal growth factor receptor was significantly down-regulated in dcSSc and showed the strongest negative correlation with the MRSS, being predictive of the score's course over time, whereas α1 -antichymotrypsin was significantly up-regulated in dcSSc and showed the strongest positive correlation with the MRSS. Furthermore, higher levels of cancer antigen 15-3 correlated with more severe ILD, based on findings of reduced forced vital capacity and higher scores of disease activity on high-resolution computed tomography. Only 14 genes showed significant differential expression in the same direction in serum protein and whole blood RNA gene expression analyses.Diffuse cutaneous SSc has a distinct serum protein profile with prominent dysregulation of proteins related to fibrosis and immune cell adhesion/diapedesis. The differential expression for most serum proteins in SSc is likely to originate outside the peripheral blood cells.
Real-World Clinical Outcomes in Previously Untreated and Minimally Treated Patients with Congenital Factor VIII Deficiency: The San Diego Experience
Authors: Kelly A Bush, Hilda Ding, Kate O'Flaherty-Keese, Rosalie Brooks, Katharine Farrow, Jovanee Recendez, Jacqueline Limjoco, Courtney D Thornburg
Journal: Blood (2020)
Association of DLL1 with type 1 diabetes in patients characterized by low polygenic risk score
Authors: Jingchun Qu, Hui-Qi Qu, Jonathan P. Bradfield, Joseph T. Glessner, Xiao Chang, Lifeng Tian, Michael E. March, Jeffrey D. Roizen, Patrick M. Sleiman, Hakon Hakonarson
Journal: Metabolism (2020)
Reversing Clonal Hematopoiesis and Associated Atherosclerotic Disease By Targeted Antibody-Drug-Conjugate (ADC) Conditioning and Transplant
Authors: Karin Gustafsson, Catherine S Rhee, Elizabeth W Scadden, Vanessa Frodermann, Rahul Palchaudhuri, Sharon L. Hyzy, Jennifer L Proctor, Geoff O Gillard, Anthony E Boitano, Michael P. Cooke, Matthias Nahrendorf, David T. Scadden
Journal: Blood (2020)
The Miracle Moment
Authors: Nicole S. Torres
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Walmart sues US government, claiming opioid rules are unclear
Authors: Owen Dyer
Journal: BMJ (2020)

America’s biggest retail chain, Walmart, which operates more than 5000 pharmacies in its stores, is suing the US Department of Justice and Drug Enforcement Agency to pre-empt an anticipated government lawsuit or prosecution over its filling of opioid prescriptions.

Walmart is one of several pharmacy and drug distribution companies that have drawn official criticism or been sued by state or federal governments for allegedly ignoring suspicious prescribing patterns that they had a duty to report, such as doctors whose patients were all taking painkillers, or stores whose opioid sales could not be feasibly explained by the medical needs of the …
Survival Outcomes for Plasmablastic Lymphoma: An International, Multicentre Study By the Australasian Lymphoma Alliance
Authors: Pietro R Di Ciaccio, Mark N. Polizzotto, Kate Cwynarski, Cathy Burton, Awachana Jiamsakul, Mark Bower, John Kuruvilla, Silvia Montoto, Pam McKay, Wendy Osborne, Sam Milliken, Kim Linton, Kate Manos, Shireen Kassam, Nicole Wong Doo, Anne-Marie Watson, Pasquale L Fedele, Costas K. Yannakou, Stewart Hunt, Hanna Renshaw, Nisha Thakrar, Alexandra Smith, Daniel Painter, Alice Maxwell, Qin Liu, Rageshri Dhairyawan, Graeme Ferguson, Keir Pickard, Nada Hamad
Journal: Blood (2020)