tbuckley/cabot-search huggingface dataset:
Health Outcomes With Vitamin D Supplementation—Reply
Authors: Anika Lucas, Myles Wolf
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
Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns
Authors: Stephen J. Galli, Nicolas Gaudenzio, Mindy Tsai
Journal: Annual Review of Immunology (2020)

Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.
Phase I Study of TAK-659, an Investigational, Dual SYK/FLT3 Inhibitor, in Patients with B-Cell Lymphoma
Authors: Leo I. Gordon, Jason B. Kaplan, Rakesh Popat, Howard A. Burris, Silvia Ferrari, Sumit Madan, Manish R. Patel, Giuseppe Gritti, Dima El-Sharkawi, Ian Chau, John A. Radford, Jaime Pérez de Oteyza, Pier Luigi Zinzani, Swaminathan Iyer, William Townsend, Reem Karmali, Harry Miao, Igor Proscurshim, Shining Wang, Yujun Wu, Kate Stumpo, Yaping Shou, Cecilia Carpio, Francesc Bosch
Journal: Clinical Cancer Research (2020)

TAK-659 is an investigational, dual SYK/FLT3 inhibitor with preclinical activity in B-cell malignancy models. This first-in-human, dose-escalation/expansion study aimed to determine the safety, tolerability, MTD/recommended phase II dose (RP2D), and preliminary efficacy of TAK-659 in relapsed/refractory solid tumors and B-cell lymphomas.Patients received continuous, once-daily oral TAK-659, 60-120 mg in 28-day cycles, until disease progression or unacceptable toxicity. The study applied an accelerated dose-escalation design to determine the MTD and RP2D. In the expansion phase, patients with lymphoma were enrolled in five disease cohorts at the MTD.Overall, 105 patients were enrolled [dose escalation, n = 36 (solid tumors, n = 19; lymphoma, n = 17); expansion, n = 69]. The MTD was 100 mg once daily. TAK-659 absorption was fast (Tmax ∼2 hours) with a long terminal half-life (∼37 hours). Exposure generally increased with dose (60-120 mg), with moderate variability. The most common treatment-related adverse events were generally asymptomatic and reversible elevations in clinical laboratory values. Among 43 response-evaluable patients with diffuse large B-cell lymphoma, 8 (19%) achieved a complete response (CR) with an overall response rate (ORR) of 28% [23% intent-to-treat (ITT)]. Responses were seen in both de novo and transformed disease and appeared independent of cell-of-origin classification. Among 9 response-evaluable patients with follicular lymphoma, 2 (22%) achieved CR with an ORR of 89% (57% ITT).TAK-659 has single-agent activity in patients with B-cell lymphoma. Further studies of the drug in combination, including an evaluation of the biologically optimal and safest long-term dose and schedule, are warranted.
Loss of a Negative Feedback Loop between IRF8 and AR Promotes Prostate Cancer Growth and Enzalutamide Resistance
Authors: Hongxi Wu, Linjun You, Yan Li, Zhili Zhao, Guangjiang Shi, Zhen Chen, Zhuo Wang, Xianjing Li, Shijia Du, Wanli Ye, Xiaofang Gao, Jingjing Duan, Yan Cheng, Weiyan Tao, Jinsong Bian, Jin-Rong Zhou, Qingyi Zhu, Yong Yang
Journal: Cancer Research (2020)

Abstract In incurable castration-resistant prostate cancer (CRPC), resistance to the novel androgen receptor (AR) antagonist enzalutamide is driven mainly by AR overexpression. Here we report that the expression of interferon regulatory factor 8 (IRF8) is increased in primary prostate cancer but decreased in CRPC compared with normal prostate tissue. Decreased expression of IRF8 positively associated with CRPC progression and enzalutamide resistance. IRF8 interacted with AR and promoted its degradation via activation of the ubiquitin/proteasome systems. Epigenetic knockdown of IRF8 promoted AR-mediated prostate cancer progression and enzalutamide resistance in vitro and in vivo. Furthermore, IFNα increased expression of IRF8 and improved the efficacy of enzalutamide in CRPC by targeting the IRF8–AR axis. We also provide preliminary evidence for the efficacy of IFNα with hormonotherapy in a clinical study. Collectively, this study identifies IRF8 both as a tumor suppressor in prostate cancer pathogenesis and a potential alternative therapeutic option to overcome enzalutamide resistance. Significance: These findings identify IRF8-mediated AR degradation as a mechanism of resistance to AR-targeted therapy, highlighting the therapeutic potential of IFNα in targeting IRF8–AR axis in CRPC.
A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
Authors: Ricardo Sánchez, Jordi Ribera, Mireia Morgades, Rosa Ayala, Esther Onecha, Yanira Ruiz-Heredia, Alexandra Juárez-Rufián, Rodrigo de Nicolás, José Sánchez-Pina, Susana Vives, Lurdes Zamora, Santiago Mercadal, Rosa Coll, Marta Cervera, Olga García, Josep-Maria Ribera, Joaquín Martínez-López
Journal: Blood Cancer Journal (2020)

Abstract BCR-ABL1 -like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1 -like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1 -like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1 -like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1 / CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12–84 years) were classified as BCR-ABL1 -like (25%) based on heatmap clustering, with significant overexpression of ENAM , IGJ , and CRLF2 ( P ≤ 0.001). The BCR-ABL1 -like subgroup accounted for 29% of 15–60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1 -like ALL signature had a higher rate of relapse and lower complete response duration than non- BCR-ABL1 -like patients ( P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1 -like ALL that correlates with adverse prognosis in adult patients with ALL.
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer
Authors: Seth J. Parker, Caroline R. Amendola, Kate E.R. Hollinshead, Qijia Yu, Keisuke Yamamoto, Joel Encarnación-Rosado, Rebecca E. Rose, Madeleine M. LaRue, Albert S.W. Sohn, Doug E. Biancur, Joao A. Paulo, Steven P. Gygi, Drew R. Jones, Huamin Wang, Mark R. Philips, Dafna Bar-Sagi, Joseph D. Mancias, Alec C. Kimmelman
Journal: Cancer Discovery (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) evolves a complex microenvironment comprised of multiple cell types, including pancreatic stellate cells (PSC). Previous studies have demonstrated that stromal supply of alanine, lipids, and nucleotides supports the metabolism, growth, and therapeutic resistance of PDAC. Here we demonstrate that alanine cross-talk between PSCs and PDAC is orchestrated by the utilization of specific transporters. PSCs utilize SLC1A4 and other transporters to rapidly exchange and maintain environmental alanine concentrations. Moreover, PDAC cells upregulate SLC38A2 to supply their increased alanine demand. Cells lacking SLC38A2 fail to concentrate intracellular alanine and undergo a profound metabolic crisis resulting in markedly impaired tumor growth. Our results demonstrate that stromal–cancer metabolic niches can form through differential transporter expression, creating unique therapeutic opportunities to target metabolic demands of cancer. Significance: This work identifies critical neutral amino acid transporters involved in channeling alanine between pancreatic stellate and PDAC cells. Targeting PDAC-specific alanine uptake results in a metabolic crisis impairing metabolism, proliferation, and tumor growth. PDAC cells specifically activate and require SLC38A2 to fuel their alanine demands that may be exploited therapeutically. This article is highlighted in the In This Issue feature, p. 890
Complement Receptor Targeted Liposomes Encapsulating the Liver X Receptor Agonist GW3965 Accumulate in and Stabilize Atherosclerotic Plaques
Authors: Naomi Benne, Renata Martins Cardoso, Aimee L. Boyle, Alexander Kros, Wim Jiskoot, Johan Kuiper, Joke Bouwstra, Miranda Van Eck, Bram Slütter
Journal: Advanced Healthcare Materials (2020)

Atherosclerosis is characterized by the retention of lipids in foam cells in the arterial intima. The liver X receptor (LXR) agonist GW3965 is a promising therapeutic compound, since it induces reverse cholesterol transport in foam cells. However, hepatic LXR activation increases plasma and liver lipid levels, inhibiting its clinical development. Herein, a formulation that specifically enhances GW3965 deposition in the atherosclerotic lesion is aimed to be developed. GW3965 is encapsulated in liposomes functionalized with the cyclic peptide Lyp-1 (CGNKRTRGC), which binds the p32 receptor expressed on foam cells. These liposomes show preferential uptake by foam cells in vitro and higher accumulation in atherosclerotic plaques in mice compared to non-targeted liposomes as determined by in vivo imaging. Flow cytometry analysis of plaques reveals increased retention of Lyp-1 liposomes in atherosclerotic plaque macrophages compared to controls (p < 0.05). Long term treatment of established plaques in LDLR -/- mice with GW3965-containing Lyp-1 liposomes significantly reduces plaque macrophage content by 50% (p < 0.01). Importantly, GW3965-containing Lyp-1 liposomes do not increase plasma or hepatic lipid content. Thus, GW3965-containing Lyp-1 liposomes successfully target the atherosclerotic macrophages allowing plaque stabilization without commonly observed side effects of LXR agonists.
Protective effects of dietary fish‐oil supplementation on skin inflammatory and oxidative stress biomarkers induced by fine particulate air pollution: a pilot randomized, double‐blind, placebo‐controlled trial*
Authors: Z. Lin, Y. Niu, Y. Jiang, B. Chen, L. Peng, T. Mi, N. Huang, W. Li, D. Xu, R. Chen, H. Kan
Journal: British Journal of Dermatology (2020)

Exposure to fine particulate matter (with an aerodynamic diameter ≤ 2·5 μm, PM2·5 ) air pollution has been associated with skin-related diseases or disorders.To evaluate the potential skin-protective effects of fish-oil supplementation against PM2·5 exposure.This is an exploratory analysis based on a pilot randomized, double-blind, placebo-controlled trial among 65 healthy young adults between September 2017 and January 2018 in Shanghai, China. We randomly assigned participants to take either fish oil or placebo 2·5 g daily for four consecutive months. Four rounds of skin D-Squame® tape samples were collected in the last 2 months, and five secondary biomarkers of skin inflammation and oxidative stress were measured. Fixed-site PM2·5 concentrations on campus were measured in real time. We used linear mixed-effect models to analyse the associations between short-term PM2·5 exposure and biomarkers in each group.The 24-h average PM2·5 concentration was 34·68 ± 15·83 μg m-3 . There were generally weaker associations between PM2·5 and biomarkers in the fish-oil group than in the placebo group, but the associations and the between-group differences varied by biomarkers and lag periods. Compared with the placebo group, for a 10-μg m-3 increase in PM2·5 concentration, the increments of interleukin-1α and carbonyl protein in the fish-oil group were 41·55% smaller [95% confidence interval (CI) 4·61-78·48%] at lag 0-48 h and 22·01% smaller (95% CI 11·25-32·77%) at lag 0-24 h, respectively. No significant between-group differences were observed for other biomarkers.This study suggested that dietary fish-oil supplementation may improve biomarkers of skin inflammation and oxidative-stress response to short-term PM2·5 exposure.
Knowledge and attitudes toward transgender community among speech-language pathologists in India: A questionnaire-based exploration
Authors: Dhanshree R. Gunjawate, Radish B. Kumar, Rohit Ravi, Lakshmi S. Kunnath
Journal: International Journal of Transgender Health (2020)

Background: During the transition process, transgender individuals may require voice and communication services. Speech-language pathologists are increasingly involved in rendering clinical services and assisting transgender clients in voice and communication therapy. Previous studies in different countries have highlighted the lack of competence expressed by the speech-language pathologists toward serving the members of the lesbian, gay, bisexual, transgender, and queer communities. Presently, no such findings are available in the Indian context. Thus, a need was felt for identifying the concerns toward treatment for transgender individuals in speech-language pathology settings in India. Aim: The aim of the present study was to assess the knowledge, comfort levels and attitudes of speech-language pathologists practicing in India regarding the transgender community. Method: An online survey method was used to assess the knowledge and attitudes among speech-language pathologists working in India toward the transgender community. Results: The findings of the study revealed higher comfort levels as compared to self-rated knowledge levels in addressing issues related to transgender healthcare. Evidence-based practices toward transgender healthcare emerged as the topic needing more information. The study also helped to identify several moral beliefs and practices for voice therapy for the transgender population. Conclusion: There is a strong need to educate the speech language pathologists toward transgender healthcare in order to promote better cultural competence. The findings of the present study help to identify the lacunae in knowledge as well as to highlight the need to have continuing education programs in this area.
Exploring Circulating Tumor Cells in Cholangiocarcinoma Using a Novel Glycosaminoglycan Probe on a Microfluidic Platform
Authors: Priya Gopinathan, Nai‐Jung Chiang, Anandaraju Bandaru, Anirban Sinha, Wen‐Yen Huang, Shang‐Cheng Hung, Yan‐Shen Shan, Gwo‐Bin Lee
Journal: Advanced Healthcare Materials (2020)

The search of alternative approaches to epithelial cell adhesion molecule (EpCAM), for the isolation of circulating tumor cells (CTC), is on the rise. This work attempts at evaluating the feasibility of using a new glycosaminoglycan, SCH45, as a probe to isolate CTCs from the peripheral blood of 65 advanced/metastatic cholangiocarcinoma (CCA) patients. The positive enrichment of CTCs from 1 mL of blood using SCH45-bound magnetic beads and subsequent staining on an integrated microfluidic platform is demonstrated. Results detailing CTC concentrations averaging ≥1 CTCs mL-1 of blood are shown, and a conventional protein biomarker, EpCAM, has been used to corroborate the finding that 100% of the patients possess CTCs in their blood. Studies detailing the use of CTCs in the prognostic monitoring and treatment effectiveness of advanced/metastatic CCA are scarce, and the isolation of CTCs from all CCA patients tested has not been reported yet. A strong correlation between CTC counts and disease progression at the time of and/or in advance of radiographic imaging in patients receiving chemotherapy is also reported. This study is one of its kind with the new probe and reduced sample volume and has potential for use in CCA diagnosis and prognosis in the near future.
ExpansionHunter Denovo: a computational method for locating known and novel repeat expansions in short-read sequencing data
Authors: Egor Dolzhenko, Mark F. Bennett, Phillip A. Richmond, Brett Trost, Sai Chen, Joke J. F. A. van Vugt, Charlotte Nguyen, Giuseppe Narzisi, Vladimir G. Gainullin, Andrew M. Gross, Bryan R. Lajoie, Ryan J. Taft, Wyeth W. Wasserman, Stephen W. Scherer, Jan H. Veldink, David R. Bentley, Ryan K. C. Yuen, Melanie Bahlo, Michael A. Eberle
Journal: Genome biology (2020)

Abstract Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide repeat expansion detection. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference repeat expansions not discoverable via existing methods.
Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria
Authors: Xiao-Yu Cheng, Sangita Biswas, Juan Li, Cheng-Jie Mao, Olga Chechneva, Jing Chen, Kai Li, Jiao Li, Jin-Ru Zhang, Chun-Feng Liu, Wen-Bin Deng
Journal: Translational Neurodegeneration (2020)

Abstract Background Parkinson’s disease (PD) is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra region of the brain. Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfolded α-synuclein aggregations. Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD. However, there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function. In addition, the half-life of mitochondria varies between days to a few weeks. Thus, identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes. In this study, we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD. Methods We generated DA neurons and astrocytes from human iPSCs and hESCs. We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer, as well as the neuroprotective effect of mitochondrial transfer. We employed immunocytochemistry and FACS analysis to track mitochondria. Results We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media (ACM) can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model. Specifically, we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media. Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway. Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone. When rotenone injured neurons were cultured in presence of ACM depleted of mitochondria (by ultrafiltration), the neuroprotective effects were abolished. Conclusions Our studies provide the proof of principle that iPSCs-derived astrocytes can act as mitochondria donor to the injured DA neurons and attenuate pathology. Using iPSCs derived astrocytes as a donor can provide a novel strategy that can be further developed for cellular therapy for PD.
Hospitalization for Lactic Acidosis Among Patients With Reduced Kidney Function Treated With Metformin or Sulfonylureas
Authors: Patricia Y. Chu, Amber J. Hackstadt, Jonathan Chipman, Marie R. Griffin, Adriana M. Hung, Robert A. Greevy, Carlos G. Grijalva, Tom Elasy, Christianne L. Roumie
Journal: Diabetes Care (2020)

To compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function.
Recommendations From the USPSTF for Prevention and Cessation of Tobacco Use in Children and Adolescents
Authors: James D. Sargent, Jennifer B. Unger, Adam M. Leventhal
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
Pooling of samples for testing for SARS-CoV-2 in asymptomatic people
Authors: Stefan Lohse, Thorsten Pfuhl, Barbara Berkó-Göttel, Jürgen Rissland, Tobias Geißler, Barbara Gärtner, Sören L Becker, Sophie Schneitler, Sigrun Smola
Journal: The Lancet Infectious Diseases (2020)