tbuckley/cabot-search huggingface dataset:
Symptom Screening at Illness Onset of Health Care Personnel With SARS-CoV-2 Infection in King County, Washington: The Journal of the American Medical Association
Authors: Eric J. M. D. M. S. M. P. H. Chow, Noah G. M. D. Schwartz, Farrell A. D. O. M. S. Tobolowsky, Rachael L. T. M. D. Zacks, Melinda M. S. N. Huntington-Frazier, Sujan C. M. D. Reddy, Agam K. M. D. Rao
Journal: JAMA (2020)
Cellular and pathological heterogeneity of primary tauopathies
Authors: Dah-eun Chloe Chung, Shanu Roemer, Leonard Petrucelli, Dennis W. Dickson
Journal: Molecular Neurodegeneration (2021)

Abstract Microtubule-associated protein tau is abnormally aggregated in neuronal and glial cells in a range of neurodegenerative diseases that are collectively referred to as tauopathies. Multiple studies have suggested that pathological tau species may act as a seed that promotes aggregation of endogenous tau in naïve cells and contributes to propagation of tau pathology. While they share pathological tau aggregation as a common feature, tauopathies are distinct from one another with respect to predominant tau isoforms that accumulate and the selective vulnerability of brain regions and cell types that have tau inclusions. For instance, primary tauopathies present with glial tau pathology, while it is mostly neuronal in Alzheimer’s disease (AD). Also, morphologies of tau inclusions can greatly vary even within the same cell type, suggesting distinct mechanisms or distinct tau conformers in each tauopathy. Neuropathological heterogeneity across tauopathies challenges our understanding of pathophysiology behind tau seeding and aggregation, as well as our efforts to develop effective therapeutic strategies for AD and other tauopathies. In this review, we describe diverse neuropathological features of tau inclusions in neurodegenerative tauopathies and discuss what has been learned from experimental studies with mouse models, advanced transcriptomics, and cryo-electron microscopy (cryo-EM) on the biology underlying cell type-specific tau pathology.
26711 Impact of biopsy and provider training on diagnostic accuracy of cutaneous immune-related adverse events
Authors: Jordan T. Said, Leah L. Thompson, Edward B. Li, Jaewon Yoon, Nira A. Krasnow, Gabriel E. Molina, Nicole J. Polyakov, Ruth K. Foreman, R. LeBoeuf, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2021)
Intravitreal Pharmacotherapies for Diabetic Macular Edema
Authors: Justis P. Ehlers, Steven Yeh, Maureen G. Maguire, Justine R. Smith, Prithvi Mruthyunjaya, Nieraj Jain, Leo A. Kim, Christina Y. Weng, Christina J. Flaxel, Scott D. Schoenberger, Stephen J. Kim
Journal: Ophthalmology (2021)
In vitro data suggest that Indian delta variant B.1.617 of SARS‐CoV‐2 escapes neutralization by both receptor affinity and immune evasion
Authors: Gilles Augusto, Mona O. Mohsen, Simon Zinkhan, Xuelan Liu, Monique Vogel, Martin F. Bachmann
Journal: Allergy (2021)

Abstract Background Emerged mutations can be attributed to increased transmissibility of the B.1.617 and B.1.36 Indian delta variants of SARS‐CoV‐2, most notably substitutions L452R/E484Q and N440K, respectively, which occur in the receptor‐binding domain (RBD) of the Spike (S) fusion glycoprotein. Objective We aimed to assess the effects of mutations L452R/E484Q and N440K (as well as the previously studied mutation E484K present in variants B.1.351 and P.1) on the affinity of RBD for ACE2, SARS‐CoV‐2 main receptor. We also aimed to assess the ability of antibodies induced by natural infection or by immunization with BNT162b2 mRNA vaccine to recognize the mutated versions of the RBD, as well as blocking the interaction RBD‐ACE2, an important surrogate readout for virus neutralization. Methods To this end, we produced recombinant wild‐type RBD, as well as RBD containing each of the mutations L452R/E484Q, N440K, or E484K (the latest present in variants of concern B.1.351 and P.1), as well as the ectodomain of ACE2. Using Biolayer Interferometry (BLI), we measured the binding affinity of RBD for ACE2 and the ability of sera from COVID‐19 convalescent donors or subjects immunized with BNT162b2 mRNA vaccine to block this interaction. Finally, we correlated these results with total anti‐RBD IgG titers measured from the same sera by direct ELISA. Results The binding assays showed L452R/E484Q double‐mutant RBD to interact with ACE2 with higher affinity (K D = 4.6 nM) than wild‐type (K D = 21.3 nM) or single mutants N440K (K D = 9.9 nM) and E484K (K D = 19.7 nM) RBDs. Meanwhile, the anti‐RBD IgG titration resulted in lower recognition of mutants E484K and L452R/E484Q by infection‐induced antibodies, whereas only mutant E484K was recognized less by antibodies induced by vaccination. More interestingly, sera from convalescent as well as immunized subjects showed reduced ability to block the interaction between ACE2 and RBD mutants E484K and L452R/E484Q, as shown by the inhibition assays. Conclusion Our data suggest that the newly emerged SARS‐CoV‐2 variant B.1.617, as well as the better‐studied variants B.1.351 and P.1 (all containing a mutation at position E484) display increased transmissibility both due to their higher affinity for the cell receptor ACE2 and their ability to partially bypass immunity generated against the wild‐type virus. For variant B.1.36 (with a point mutation at position N440), only increased affinity seems to play a role.
Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination
Authors: Ai-Ming Yu, Mei-Juan Tu
Journal: Pharmacology & Therapeutics (2021)

The concepts of developing RNAs as new molecular entities for therapies have arisen again and again since the discoveries of antisense RNAs, direct RNA-protein interactions, functional noncoding RNAs, and RNA-directed gene editing. The feasibility was demonstrated with the development and utilization of synthetic RNA agents to selectively control target gene expression, modulate protein functions or alter the genome to manage diseases. Rather, RNAs are labile to degradation and cannot cross cell membrane barriers, making it hard to develop RNA medications. With the development of viable RNA technologies, such as chemistry and pharmaceutics, eight antisense oligonucleotides (ASOs) (fomivirsen, mipomersen, eteplirsen, nusinersen, inotersen, golodirsen, viltolarsen and casimersen), one aptamer (pegaptanib), and three small interfering RNAs (siRNAs) (patisiran, givosiran and lumasiran) have been approved by the United States Food and Drug Administration (FDA) for therapies, and two mRNA vaccines (BNT162b2 and mRNA-1273) under Emergency Use Authorization for the prevention of COVID-19. Therefore, RNAs have become a great addition to small molecules, proteins/antibodies, and cell-based modalities to improve the public health. In this article, we first summarize the general characteristics of therapeutic RNA agents, including chemistry, common delivery strategies, mechanisms of actions, and safety. By overviewing individual RNA medications and vaccines approved by the FDA and some agents under development, we illustrate the unique compositions and pharmacological actions of RNA products. A new era of RNA research and development will likely lead to commercialization of more RNA agents for medical use, expanding the range of therapeutic targets and increasing the diversity of molecular modalities.
eBEACOPP or A-AVD in advanced Hodgkin lymphoma: (re)thinking the toxicities in the PET-driven strategies era
Authors: Jean Galtier, Pauline Brice, Krimo Bouabdallah, Françoix-Xavier Gros, Marie-Sarah Dilhuydy, Noël Milpied
Journal: The Lancet Haematology (2021)
68Ga-HER2 affibody PET/CT imaging as an option in patients whose HER2 status of any tumor in the body needs to be deciphered.
Authors: Haitao Miao, Yuyun Sun, Xichun Hu, Shaoli Song, Jian Zhang
Journal: Journal of Clinical Oncology (2021)

1045 Background: Anti-HER2 targeted agents are standard of care for HER2 positive patients with either early or advanced breast cancer. Determination of tumor HER2 status helps diagnosing and treating breast cancer. In any tumor which required this biological information, we used a novel 68 Ga-NOTA-MAL-MZHER2 ( 68 Ga-HER2) affibody PET/CT to differentiate HER2 status of each lesion in the patient body. Methods: 68 Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status of any lesions in the patient body remained to be determined. Results: Twenty-four patients were enrolled. 68 Ga-HER2 affibody PET/CT was requested by physicians due to the following reasons: 6 with multiple primary cancers (including patients who harbored two primary breast malignancies but with different HER2 status, and patients who had at least another non-breast primary other than HER2-positve breast cancer), 13 with metastases inaccessible for biopsy or repeated biopsy, 6 with inconsistent HER2 status between the primary and metastatic lesions, and 4 with different HER2-status within metastases (ICH ranging from 0-3+). Assessment report showed that the 68 Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. In 11 lesions which was pathological-confirmed HER2-positivity, 100% of the tumors were also positive with this PET/CT. The heterogeneity of 68 Ga-HER2 affibody uptake was obvious, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference among patients. Conclusions: 68 Ga-HER2 affibody PET/CT imaging is a valuable tool if HER2 status of any tumor needs to determined. We are now evaluating the 68 Ga-HER2 affibody PET/CT imaging as a non-invasive approach to classify the molecular subtype of metastatic breast cancer, and its potential application in the dynamic surveillance of anti-HER2 therapies.
Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health
Authors: Brian T. Joyce, Tao Gao, Yinan Zheng, Jiantao Ma, Shih-Jen Hwang, Lei Liu, Drew Nannini, Steve Horvath, Ake T. Lu, Norrina Bai Allen, David R. Jacobs, Myron Gross, Amy Krefman, Hongyan Ning, Kiang Liu, Cora E. Lewis, Pamela J. Schreiner, Stephen Sidney, James M. Shikany, Daniel Levy, Philip Greenland, Lifang Hou, Donald Lloyd-Jones
Journal: Circulation Research (2021)

[Figure: see text].
Other good reasons for covid-19 vaccination in pre-adolescent and adolescent populations
Authors: Federico Marchetti, Giorgio Tamburlini
Journal: BMJ (2021)

In Wilkinson and colleagues' article giving the reasons for and against covid-19 vaccination for children and adolescents 1 it is surprising that the consequences of the "secondary pandemic" on this population were not taken into account.Indeed, there are several other good reasons for vaccination of the adolescent population, whose lives have been so badly affected by containment measures.
25985 Efficacy of tildrakizumab 100 mg for PASI improvement in patients with moderate to severe plaque psoriasis: Pooled analysis using nonresponder imputation from reSURFACE 1 and 2 through week 52
Authors: Mark G. Lebwohl, Richard G.B. Langley, Rodney Sinclair, April W. Armstrong, Alan M. Mendelsohn, Stephen J. Rozzo, Jerry Bagel
Journal: Journal of the American Academy of Dermatology (2021)
Multi-omics of the esophageal microenvironment identifies signatures associated with progression of Barrett’s esophagus
Authors: Nandan P. Deshpande, Stephen M. Riordan, Claire J. Gorman, Shaun Nielsen, Tonia L. Russell, Carolina Correa-Ospina, Bentotage S. M. Fernando, Shafagh A. Waters, Natalia Castaño-Rodríguez, Si Ming Man, Nicodemus Tedla, Marc R. Wilkins, Nadeem O. Kaakoush
Journal: Genome Medicine (2021)

Abstract Background The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host. Methods Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest. Results Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment of Campylobacter species as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found between Campylobacter and napsin B aspartic peptidase. Targeted culture of Campylobacter species from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for these Campylobacter strain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to the Campylobacter isolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression. Conclusions We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.
Reporting of Race and Ethnicity in Medical and Scientific Journals
Authors: Ash Routen, Manish Pareek, Kamlesh Khunti
Journal: JAMA (2021)

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
トリオースキナーゼはフルクトースと食事耐性の脂質生成能を制御する【JST・京大機械翻訳】
Authors: Liu Lei, Li Tian, Liao Yilie, Wang Yalong, Gao Yang, Hu Haikun, Huang Haipeng, Wu Fang, Chen Ye-Guang, Xu Shuhua, Fu Suneng
Journal: Cell Metabolism (2020)
Developmental dynamics of voltage-gated sodium channel isoform expression in the human and mouse brain
Authors: Lindsay Liang, Siavash Fazel Darbandi, Sirisha Pochareddy, Forrest O. Gulden, Michael C. Gilson, Brooke K. Sheppard, Atehsa Sahagun, Joon-Yong An, Donna M. Werling, John L. R. Rubenstein, Nenad Sestan, Kevin J. Bender, Stephan J. Sanders
Journal: Genome Medicine (2021)

Genetic variants in the voltage-gated sodium channels SCN1A, SCN2A, SCN3A, and SCN8A are leading causes of epilepsy, developmental delay, and autism spectrum disorder. The mRNA splicing patterns of all four genes vary across development in the rodent brain, including mutually exclusive copies of the fifth protein-coding exon detected in the neonate (5N) and adult (5A). A second pair of mutually exclusive exons is reported in SCN8A only (18N and 18A). We aimed to quantify the expression of individual exons in the developing human brain. RNA-seq data from 783 human brain samples across development were analyzed to estimate exon-level expression. Developmental changes in exon utilization were validated by assessing intron splicing. Exon expression was also estimated in RNA-seq data from 58 developing mouse neocortical samples. In the mature human neocortex, exon 5A is consistently expressed at least 4-fold higher than exon 5N in all four genes. For SCN2A, SCN3A, and SCN8A, a brain-wide synchronized 5N to 5A transition occurs between 24 post-conceptual weeks (2nd trimester) and 6 years of age. In mice, the equivalent 5N to 5A transition begins at or before embryonic day 15.5. In SCN8A, over 90% of transcripts in the mature human cortex include exon 18A. Early in fetal development, most transcripts include 18N or skip both 18N and 18A, with a transition to 18A inclusion occurring from 13 post-conceptual weeks to 6 months of age. No other protein-coding exons showed comparably dynamic developmental trajectories. Exon usage in SCN1A, SCN2A, SCN3A, and SCN8A changes dramatically during human brain development. These splice isoforms, which alter the biophysical properties of the encoded channels, may account for some of the observed phenotypic differences across development and between specific variants. Manipulation of the proportion of splicing isoforms at appropriate stages of development may act as a therapeutic strategy for specific mutations or even epilepsy in general.
Lower blood malondialdehyde is associated with past pesticide exposure: findings in Gulf War illness and healthy controls
Authors: Beatrice Alexandra Golomb, Sridevi Devaraj, Alexis K. Messner, Hayley Jean Koslik, Jun Hee Han, Barnabas Yik
Journal: Military Medical Research (2021)

Malondialdehyde (MDA) is a candidate general marker of oxidative stress (OS). We sought to assess the relation of MDA to Gulf War illness (GWI) and to a variety of exposures. This is an observational study involving subjects from Southern California recruited from October 2011 to May 2014. MDA was assessed in 81 participants (41 GWI-cases, 40 controls). General and Gulf-specific exposures were elicited. MDA case-control comparison was restricted to 40 matched pairs. The potential association between MDA and exposures was assessed using regression analyses. Gulf-specific exposures were incorporated into a case-specific model. Plasma MDA was significantly lower in GWI-cases than controls. Composite pesticide and fuel-solvent exposures negatively predicted MDA in the total sample, as well as in the analyses that included either GWI-cases or controls only. Self-reported exposure to organophosphate (OP) nerve gas was a strong predictor for lower MDA level in veterans with GWI. Past pesticide exposures predicted lower MDA in both veterans with GWI and in healthy controls.
181. Efficient Lung Orthotopic Tumor-Growth Suppression of Oncolytic Adenovirus Complexed With RGD-Targeted Bioreducible Polymer
Journal: Molecular Therapy (2014)

Oncolytic adenoviruses (Ad) have been developed for the eradication of tumors. Although they hold much promise as a cancer therapy, they have a short blood circulation time and high liver toxicity. An effective strategy to overcome these problems has been complexing Ad with shielding materials. However, the therapeutic efficacy of the Ad complexes has also been an issue because passive accumulation does not allow for sufficient delivery of Ad to the cancer cells. To enhance the therapeutic efficacy of the polymer-coated Ads, the attachment of a targeting moiety to polymer-coated Ad vectors is inescapable. Our lab has previously reported the potential use of Arg-Gly-Asp (RGD)-targeted bioreducible polymers with a polyethylene glycol (PEG) linker for delivering oncolytic Ads. We have shown the enhanced in vitro transduction efficiency and increased cancer-killing effect with producing progeny oncolytic Ad particles. In addition, we have shown significant tumor-growth inhibition of the polymer-shielded Ad in an in vivo lung orthotopic tumor model. The shielding effect of the Ad surface with the polymers allowed evasion of host immune responses and reduction of liver toxicity. This data demonstrates that the RGD-conjugated bioreducible polymer for delivering the oncolytic Ad vectors could be utilized for cancer therapy via systemic administration.
27697 Long-term efficacy, safety, and adherence to tralokinumab treatment in moderate-to-severe atopic dermatitis for up to 3 years: Interim readout of ECZTEND, a phase 3, long-term extension trial
Authors: Andrew Blauvelt, Jean-Philippe Lacour, Darryl Toth, Vivian Laquer, Stefan Beissert, Andreas Wollenberg, Pedro Herranz, Andrew Pink, Ketty Peris, Hidehisa Saeki
Journal: Journal of the American Academy of Dermatology (2021)
28043 Roflumilast cream significantly improves chronic plaque psoriasis in patients with steroid-sensitive area involvement
Authors: Zoe D. Draelos, Mark G. Lebwohl, Charles W. Lynde, Walter K. Nahm, Kim A. Papp, David M. Pariser, Linda Stein Gold, Daniel Stewart, Robert C. Higham, Lynn Navale, David R. Berk
Journal: Journal of the American Academy of Dermatology (2021)
Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction
Authors: Nathan Mewton, François Roubille, Didier Bresson, Cyril Prieur, Claire Bouleti, Thomas Bochaton, Fabrice Ivanes, Olivier Dubreuil, Loïc Biere, Ahmad Hayek, François Derimay, Mariama Akodad, Benjamin Alos, Lamis Haider, Naoual El Jonhy, Rachel Daw, Charles De Bourguignon, Carole Dhelens, Gérard Finet, Eric Bonnefoy-Cudraz, Gabriel Bidaux, Florent Boutitie, Delphine Maucort-Boulch, Pierre Croisille, Gilles Rioufol, Fabrice Prunier, Denis Angoulvant
Journal: Circulation (2021)

Inflammation is a key factor of myocardial damage in reperfused ST-segment-elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment-elevation myocardial infarction.In this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment-elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes.We enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement-defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16-44] versus 28.4 IQR [14-40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, -8.3% to 11.1%) versus -1.1% (IQR, -8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10-28] versus 18 IQR [10-27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002).In this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03156816.