tbuckley/cabot-search huggingface dataset:
Understanding adverse events of immunotherapy: A mechanistic perspective
Authors: Kelly P. Burke, Stephanie Grebinoski, Arlene H. Sharpe, Dario A.A. Vignali
Journal: The Journal of Experimental Medicine (2020)

The treatment of many cancers has been revolutionized by immune checkpoint blockade (ICB) as a standard-of-care therapeutic. Despite many successes, a large proportion of patients treated with ICB agents experience immune-related adverse events (irAEs) in the form of clinical autoimmunity, ranging from mild to life threatening, that can limit cancer treatment. A mechanistic understanding of these irAEs is required to better treat or prevent irAEs and to predict those patients who are susceptible to irAEs. We propose several mechanisms that may contribute to the generation of irAEs: (1) preexisting susceptibility to autoimmunity, (2) aberrant presentation of "self" by the tumor, and (3) loss of tolerance driven by the tumor or tissue microenvironment.
Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes
Authors: Aurélie Carlier, Franck Phan, Anaïs Szpigel, Eric Hajduch, Joe-Elie Salem, Jérémie Gautheron, Wilfried Le Goff, Maryse Guérin, Floriane Lachkar, Vlad Ratziu, Agnès Hartemann, Pascal Ferré, Fabienne Foufelle, Olivier Bourron
Journal: Cell Reports Medicine (2020)

Plasma dihydroceramides are predictors of type 2 diabetes and related to metabolic dysfunctions, but the underlying mechanisms are not characterized. We compare the relationships between plasma dihydroceramides and biochemical and hepatic parameters in two cohorts of diabetic patients. Hepatic steatosis, steatohepatitis, and fibrosis are assessed by their plasma biomarkers. Plasma lipoprotein sphingolipids are studied in a sub-group of diabetic patients. Liver biopsies from subjects with suspected non-alcoholic fatty liver disease are analyzed for sphingolipid synthesis enzyme expression. Dihydroceramides, contained in triglyceride-rich very-low-density lipoprotein (VLDL), are associated with steatosis and steatohepatitis. Expression of sphingolipid synthesis enzymes is correlated with histological steatosis and inflammation grades. In conclusion, association of plasma dihydroceramides with nonalcoholic fatty liver might explain their predictive character for type 2 diabetes. Our results suggest a relationship between hepatic sphingolipid metabolism and steatohepatitis and an involvement of dihydroceramides in the synthesis/secretion of triglyceride-rich VLDL, a hallmark of NAFLD and type 2 diabetes dyslipidemia.
Optimizing Neonatal Nutrition in Resource-Constrained Settings
Authors: Amy Sarah Ginsburg, Valerie Flaherman
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
Abstract 13101: Left Ventricular Ejection Fraction: Range of Normal Responses During Semi-Supine Bicycle Stress Echocardiography
Authors: Mathias Claeys, Timothy Roberts, Lieven Herbots, Jan Verwerft, Kristof Lefebvre, Jens-Uwe Voigt, Hein Heidbuchel, Rik Willems, Guido Claessen, Andre La Gerche
Journal: Circulation (2018)

Introduction: Cardiac reserve (the change in LV ejection fraction with exercise) is an important prognostic parameter in heart failure. However, reference values of normal peak LV performance remai...
Bidirectional differentiation of BMSCs induced by a biomimetic procallus based on a gelatin-reduced graphene oxide reinforced hydrogel for rapid bone regeneration
Authors: Delong Jiao, Ao Zheng, Yang Liu, Xiangkai Zhang, Xiao Wang, Jiannan Wu, Wenjun She, Kaige Lv, Lingyan Cao, Xinquan Jiang
Journal: Bioactive Materials (2020)

Developmental engineering strategy needs the biomimetic composites that can integrate the progenitor cells, biomaterial matrices and bioactive signals to mimic the natural bone healing process for faster healing and reconstruction of segmental bone defects. We prepared the gelatin-reduced graphene oxide (GOG) and constructed the composites that mimicked the procallus by combining the GOG with the photo-crosslinked gelatin hydrogel. The biological effects of the GOG-reinforced composites could induce the bi-differentiation of bone marrow stromal cells (BMSCs) for rapid bone repair. The proper ratio of GOG in the composites regulated the composites' mechanical properties to a suitable range for the adhesion and proliferation of BMSCs. Besides, the GOG-mediated bidirectional differentiation of BMSCs, including osteogenesis and angiogenesis, could be activated through Erk1/2 and AKT pathway. The methyl vanillate (MV) delivered by GOG also contributed to the bioactive signals of the biomimetic procallus through priming the osteogenesis of BMSCs. During the repair of the calvarial defect
Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19
Authors: Qirui Guo, Yingchi Zhao, Junhong Li, Jiangning Liu, Xiuhong Yang, Xuefei Guo, Ming Kuang, Huawei Xia, Zeming Zhang, Lili Cao, Yujie Luo, Linlin Bao, Xiao Wang, Xuemei Wei, Wei Deng, Nan Wang, Luoying Chen, Jingxuan Chen, Hua Zhu, Ran Gao, Chuan Qin, Xiangxi Wang, Fuping You
Journal: Cell Host & Microbe (2020)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
Employee Wellness Programs—Reply
Authors: Julian Reif, Damon Jones, David Molitor
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Defining the Normal Spectrum of Electrocardiographic and Left Ventricular Adaptations in Mixed-Race Male Adolescent Soccer Players
Authors: Aneil Malhotra, David Oxborough, Prashant Rao, Gherardo Finocchiaro, Harshil Dhutia, Vivek Prasad, Chris Miller, Bernard Keavney, Michael Papadakis, Sanjay Sharma
Journal: Circulation (2020)
A novel electrocautery-enhanced delivery system for one-step endoscopic ultrasound-guided drainage of the gallbladder and bile duct using a lumen-apposing metal stent: a feasibility study
Authors: Hae Won Yoo, Seok Jung Jo, Jong Ho Moon, Yun Nah Lee, Jae Keun Park, Tae Hoon Lee, Sang-Woo Cha, Young Deok Cho, Sang-Heum Park, Se Ik Park, Seok Jeong, Don Haeng Lee
Journal: Endoscopy (2020)

Abstract Background The use of a lumen-apposing metal stent (LAMS) capable of one-step endoscopic ultrasound-guided transmural drainage (EUS-TD) can increase the effectiveness of the procedure. We evaluated the newly developed electrocautery-enhanced (EC) delivery system with a LAMS for one-step EUS-guided gallbladder drainage (EUS-GBD) or choledochoduodenostomy (EUS-CDS). Methods In the animal experiment, an EC-LAMS was advanced into the gallbladder without prior tract dilation in four pigs. A conventional LAMS was inserted in another four pigs as a control group. After the animal experiment, 17 patients underwent EUS-TD using the EC-LAMS (EUS-GBD in 10 patients, EUS-CDS in 7). The primary outcome was the technical success rate. Results In the animal study, the mean procedure time was significantly shorter in the EC-LAMS group than in the conventional LAMS group. In the human study, the overall technical success rate was 94.1 %, with one EUS-GBD failure. The clinical success rate was 100 %. The overall adverse event rate was 17.6 %. Conclusions One-step EUS-GBD or EUS-CDS using the novel EC-LAMS is a feasible approach that achieves a high success rate and maintains safety.
Sphingosine-1-Phosphate Metabolism and Signaling in Kidney Diseases
Authors: Yelena Drexler, Judith Molina, Alla Mitrofanova, Alessia Fornoni, Sandra Merscher
Journal: Journal of the American Society of Nephrology (2020)

In the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.
Delivery Mode Affects Stability of Early Infant Gut Microbiota
Authors: Caroline M. Mitchell, Chiara Mazzoni, Larson Hogstrom, Allison Bryant, Agnes Bergerat, Avital Cher, Shawna Pochan, Penelope Herman, Maureen Carrigan, Karen Sharp, Curtis Huttenhower, Eric S. Lander, Hera Vlamakis, Ramnik J. Xavier, Moran Yassour
Journal: Cell Reports Medicine (2020)

Mode of delivery strongly influences the early infant gut microbiome. Children born by cesarean section (C-section) lack Bacteroides species until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome. Here, we re-evaluate this hypothesis by comparing the microbial profiles of 75 infants born vaginally or by planned versus emergent C-section. Multiple children born by C-section have a high abundance of Bacteroides in their first few days of life, but at 2 weeks, both C-section groups lack Bacteroides (primarily according to 16S sequencing), despite their difference in exposure to the birth canal. Finally, a comparison of microbial strain profiles between infants and maternal vaginal or rectal samples finds evidence for mother-to-child transmission of rectal rather than vaginal strains. These results suggest differences in colonization stability as an important factor in infant gut microbiome composition rather than birth canal exposure.
Emerging Evidence of the Direct Association Between COVID-19 and Chilblains
Authors: Esther E. Freeman, Devon E. McMahon, Lindy P. Fox
Journal: JAMA Dermatology (2020)

Anne Herman, MD; Caroline Peeters, MD; Alexia Verroken, MD, PhD; Isabelle Tromme, MD, PhD; Dominique Tennstedt, MD; Liliane Marot, MD; Claire Dachelet, MD; Damien Gruson, PharmD, PhD; Cedric Hermans, MD, PhD; Marie Baeck, MD, PhD
BRD9 Is a Critical Regulator of Androgen Receptor Signaling and Prostate Cancer Progression
Authors: Aktan Alpsoy, Sagar M. Utturkar, Benjamin C. Carter, Alisha Dhiman, Sandra E. Torregrosa-Allen, Melanie P. Currie, Bennett D. Elzey, Emily C. Dykhuizen
Journal: Cancer Research (2020)

Abstract Switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complexes are critical regulators of chromatin dynamics during transcription, DNA replication, and DNA repair. A recently identified SWI/SNF subcomplex termed GLTSCR1/1L-BAF (GBAF; or “noncanonical BAF”, ncBAF) uniquely contains bromodomain-containing protein BRD9 and glioma tumor suppressor candidate region 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L). Recent studies have identified a unique dependency on GBAF (ncBAF) complexes in synovial sarcoma and malignant rhabdoid tumors, both of which possess aberrations in canonical BAF (cBAF) and Polybromo-BAF (PBAF) complexes. Dependencies on GBAF in malignancies without SWI/SNF aberrations, however, are less defined. Here, we show that GBAF, particularly its BRD9 subunit, is required for the viability of prostate cancer cell lines in vitro and for optimal xenograft tumor growth in vivo. BRD9 interacts with androgen receptor (AR) and CCCTC-binding factor (CTCF), and modulates AR-dependent gene expression. The GBAF complex exhibits overlapping genome localization and transcriptional targets as bromodomain and extraterminal domain–containing (BET) proteins, which are established AR coregulators. Our results demonstrate that GBAF is critical for coordinating SWI/SNF–BET cooperation and uncover a new druggable target for AR-positive prostate cancers, including those resistant to androgen deprivation or antiandrogen therapies. Significance: Advanced prostate cancers resistant to androgen receptor antagonists are still susceptible to nontoxic BRD9 inhibitors, making them a promising alternative for halting AR signaling in progressed disease.
Inhibiting CDK4/6 in Breast Cancer with Palbociclib, Ribociclib, and Abemaciclib: Similarities and Differences
Authors: C. Louwrens Braal, Elisabeth M. Jongbloed, Saskia M. Wilting, Ron H. J. Mathijssen, Stijn L. W. Koolen, Agnes Jager
Journal: Drugs (2020)

The cyclin-dependent kinase (CDK) 4/6 inhibitors belong to a new class of drugs that interrupt proliferation of malignant cells by inhibiting progression through the cell cycle. Three such inhibitors, palbociclib, ribociclib, and abemaciclib were recently approved for breast cancer treatment in various settings and combination regimens. On the basis of their impressive efficacy, all three CDK4/6 inhibitors now play an important role in the treatment of patients with HR+, HER2- breast cancer; however, their optimal use still needs to be established. The three drugs have many similarities in both pharmacokinetics and pharmacodynamics. However, there are some differences on the basis of which the choice for a particular CDK4/6 inhibitor for an individual patient can be important. In this article, the clinical pharmacokinetic and pharmacodynamic profiles of the three CDK4/6 inhibitors are reviewed and important future directions of the clinical applicability of CDK4/6 inhibitors will be discussed.
Patients with COVID-19 and Kidney Disease: Who Fared Best?
Authors: Micaela Antonius, David Jackson, Sadananda V. Aithal, Michael T. Shiel, Huw Davies
Journal: Journal of the American Society of Nephrology (2020)

Antonius, Micaela; Jackson, David; Aithal, Sadananda V.; Shiel, Michael T.; Davies, Huw Author Information
Glomerular Filtration Barrier Dysfunction in an RNA Virus-Induced Glomerulopathy Resembles Findings of Common Nephrotic Syndromes
Authors: Christian Nusshag, Alisa Stütz, Stefan Hägele, Claudius Speer, Florian Kälble, Christoph Eckert, Christian Morath, Jochen Reiser, Martin G. Zeier, Ellen Krautkrämer
Journal: Journal of the American Society of Nephrology (2020)

Background: Virally induced kidney dysfunction is highlighted by the alarming incidence of SARS-CoV-2 associated acute renal disease including nephrotic syndrome (NS)  Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) are elevated in COVID patients and provide prognostic insights  SuPAR is also involved in proteinuric kidney diseases such as focal segmental glomerulosclerosis in which podocytes effacement/injury is a common feature  Hantavirus-induced hemorrhagic fever with renal syndrome (HFRS) represents another RNA virus-induced disease with acute kidney injury and NS  The exact pathophysiology of proteinuria is, however, unclear  We hypothesized that hantavirus infection results in podocyte injury and a dysfunctional glomerular filtration barrier (GFB), similar to findings in common NS  Methods: Renal biopsy specimens were analyzed by light and electron microscopy  Urinary nephrin and serum suPAR were measured over time in 26 patients with HFRS and 18 healthy controls  Results: Hantavirus patients showed significantly increased urinary nephrin, immunoglobulin G (IgG), a1-microglobulin (a1-MG) and serum suPAR concentrations compared to healthy controls  Furthermore, nephrin and IgG levels were significantly higher in patients with severe than with mild proteinuria  Differences in a1-MG levels, however, disappeared after normalization to urinary creatinine  Urinary nephrin levels as a marker for podocyte damage correlated strongly with biomarkers of non-selective glomerular proteinuria  Interestingly, suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a potential pathophysiological mediator in GFB dysfunction in response to RNA virus infection  The main finding in microscopy analyses was a focal foot process effacement  Proteinuria and kidney dysfunction recovered autonomously in all patients  Conclusions: Hantavirus infection causes a podocyte injury leading to GFB dysfunction  A better understanding of transient virally induced proteinuria syndromes and their often self-limiting disease character may generate new therapeutic approaches for NS
Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial
Authors: H.-Y. Yhim, T. Kim, S.J. Kim, H.-J. Shin, Y. Koh, J.S. Kim, J. Park, G.S. Park, W.S. Kim, J.H. Moon, D.-H. Yang
Journal: Annals of Oncology (2020)
幹細胞移植後の肝中心静脈閉塞症(VOD)の早期発見のための携行カラードップラー超音波検査の有用性
Authors: Hashiguchi M, Ono N, Imamura R, Yakushiji K, Yoshimoto K, Ogata H, Okamura T, Sata M, Kuroiwa M, Higuchi M, Kato K, Taniguchi S, Gondo H, Harada M
Journal: Blood (2003)
パート1:エグゼクティブ・サマリー 心肺機能蘇生と救急心血管ケアに関する米国心臓病協会ガイドライン2010年版
Authors: M Field John, Hazinski Mary Fran, R Sayre Michael, Chameides Leon, M Schexnayder Stephen, Hemphill Robin, A Samson Ricardo, Kattwinkel John, A Berg Robert, Bhanji Farhan, M Cave Diana, C Jauch Edward, J Kudenchuk Peter, W Neumar Robert, Peberdy Mary Ann, M Perlman Jeffrey, Sinz Elizabeth, H Travers Andrew, D Berg Marc, E Billi John, Eigel Brian, W Hickey Robert, E Kleinman Monica, S Link Mark, J Morrison Laurie, E O’Connor Robert, Shuster Michael, W Callaway Clifton, Cucchiara Brett, D Ferguson Jeffrey, D Rea Thomas, L Vanden Hoek Terry
Journal: Circulation (2010)
Exposure to soil environments during earlier life stages is distinguishable in the gut microbiome of adult mice
Authors: Wenjun Liu, Zheng Sun, Chen Ma, Jiachao Zhang, ChenChen Ma, Yinqi Zhao, Hong Wei, Shi Huang, Heping Zhang
Journal: Gut Microbes (2020)

Environmental exposure during earlier life stages can govern the assembly and development of gut microbiota, yet it is insufficiently understood. In this study, ex-germ-free mice were cohoused with distinct soil-microbiota (from desert, steppe, and forest) beddings within 60 days after birth and subsequently transferred to new soil beddings from 60 to 90th day. Using metagenomic shotgun sequencing, firstly, we found soil microbes from natural environments (birthplace) greatly influenced the gut community assembly in the housing experiment. About 27% microbial species and 12% functional components that associated with birthplaces at Day 60 were still discriminatory of birthplaces after transferring mice to new environments. Moreover, prior soil-exposure types are associated with the magnitude of temporal microbiome change due to environmental shifts. The appropriate soil-exposure (e.g., steppe) might help mice gut microbiome adapt to changing environments or host development. Our study demonstrated the continuous soil-exposure history earlier is associated with the gut microbiome individuality and development later.
FDG PET/CT of Benign Psammomatous Meningioma Effacing the Medulla
Authors: Tzyy-Ling Chuang, Jin-Cherng Chen, Yu-Ruei Chen, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2020)

A 62-year-old woman had progressively developing throbbing right neck pain for 1 year. The pain radiated to the right suboccipital area, sometimes accompanied by breathlessness. To rule out cancer, patient received FDG PET/CT, which showed an intraspinal cord intense FDG-avid calcified mass at the level of the first cervical spine, mimicking malignancy. MRI showed it effacing the medulla; surgery is probably a challenge. She received laminectomy with tumor removal; pathology showed psammomatous meningioma, World Health Organization grade I. This case suggests that benign spinal cord psammomatous meningioma with calcification may show high FDG uptake, mimicking malignancy.