tbuckley/cabot-search huggingface dataset:
<i>α</i>6-Containing GABA<sub>A</sub>Receptors: Functional Roles and Therapeutic Potentials
Authors: Werner Sieghart, Lih-Chu Chiou, Margot Ernst, Jure Fabjan, Miroslav M. Savić, Ming Tatt Lee
Journal: Pharmacological Reviews (2022)

GABA<sub>A</sub> receptors containing the <i>α</i>6 subunit are highly expressed in cerebellar granule cells and less abundantly in many other neuronal and peripheral tissues. Here, we for the first time summarize their importance for the functions of the cerebellum and the nervous system. The cerebellum is not only involved in motor control but also in cognitive, emotional, and social behaviors. <i>α</i>6<i>βγ</i>2 GABA<sub>A</sub> receptors located at cerebellar Golgi cell/granule cell synapses enhance the precision of inputs required for cerebellar timing of motor activity and are thus involved in cognitive processing and adequate responses to our environment. Extrasynaptic <i>α</i>6<i>βδ</i> GABA<sub>A</sub> receptors regulate the amount of information entering the cerebellum by their tonic inhibition of granule cells, and their optimal functioning enhances input filtering or contrast. The complex roles of the cerebellum in multiple brain functions can be compromised by genetic or neurodevelopmental causes that lead to a hypofunction of cerebellar <i>α</i>6-containing GABA<sub>A</sub> receptors. Animal models mimicking neuropsychiatric phenotypes suggest that compounds selectively activating or positively modulating cerebellar <i>α</i>6-containing GABA<sub>A</sub> receptors can alleviate essential tremor and motor disturbances in Angelman and Down syndrome as well as impaired prepulse inhibition in neuropsychiatric disorders and reduce migraine and trigeminal-related pain via <i>α</i>6-containing GABA<sub>A</sub> receptors in trigeminal ganglia. Genetic studies in humans suggest an association of the human GABA<sub>A</sub> receptor <i>α</i>6 subunit gene with stress-associated disorders. Animal studies support this conclusion. Neuroimaging and post-mortem studies in humans further support an involvement of <i>α</i>6-containing GABA<sub>A</sub> receptors in various neuropsychiatric disorders, pointing to a broad therapeutic potential of drugs modulating <i>α</i>6-containing GABA<sub>A</sub> receptors. <h3>Significance Statement</h3> <i>α</i>6-Containing GABA<sub>A</sub> receptors are abundantly expressed in cerebellar granule cells, but their pathophysiological roles are widely unknown, and they are thus out of the mainstream of GABA<sub>A</sub> receptor research. Anatomical and electrophysiological evidence indicates that these receptors have a crucial function in neuronal circuits of the cerebellum and the nervous system, and experimental, genetic, post-mortem, and pharmacological studies indicate that selective modulation of these receptors offers therapeutic prospects for a variety of neuropsychiatric disorders and for stress and its consequences.
The long road to leptin
Authors: Jeffrey Friedman
Journal: Journal of Clinical Investigation (2016)

Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients. Leptin acts on neurons in the hypothalamus and elsewhere to elicit its effects, and mutations that affect the function of this neural circuit cause Mendelian forms of obesity. Leptin levels fall during starvation and elicit adaptive responses in many other physiologic systems, the net effect of which is to reduce energy expenditure. These effects include cessation of menstruation, insulin resistance, alterations of immune function, and neuroendocrine dysfunction, among others. Some or all of these effects are also seen in patients with constitutively low leptin levels, such as occur in lipodystrophy. Leptin is an approved treatment for generalized lipodystrophy, a condition associated with severe metabolic disease, and has also shown potential for the treatment of other types of diabetes. In addition, leptin restores reproductive capacity and increases bone mineral density in patients with hypothalamic amenorrhea, an infertility syndrome in females. Most obese patients have high endogenous levels of leptin, in some instances as a result of mutations in the neural circuit on which leptin acts, though in most cases, the pathogenesis of leptin resistance is not known. Obese patients with leptin resistance show a variable response to exogenous leptin but may respond to a combination of leptin plus amylin. Overall, the identification of leptin has provided a framework for studying the pathogenesis of obesity in the general population, clarified the nature of the biologic response to starvation, and helped to advance our understanding of the neural mechanisms that control feeding.
Retracted: Multifunctional Polymeric Nanosystems for Dual‐Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors
Authors: Fatima Zohra Dahmani, Yan Xiao, Juan Zhang, Yao Yu, Jianping Zhou, Jing Yao
Journal: Advanced Healthcare Materials (2021)

In the original version of this article, there was a mistake in Figure 7A due to errors during the compilation of the images.For the data of HIF-1, the photo of group b was wrongly placed in the photo position of group c in the process of combining images.A similar error caused by carelessness in the process of regrouping pictures also occurred in the CD31 data.The photo of group d was incorrectly placed in the photo position of group e in the process of combining images.The correct figure is shown below.This mistake does not affect the results, discussions and conclusions published in this work, and the authors apologize for any confusion caused.
Impact on health care of curative treatment by radiofrequency catheter ablation of accessory pathway: Long-term results Dominique Boulmier, Sr., Philippe Mabo, Sr., Dominique Pavin, Sr., Christophe Leclercq, Sr., Christine Alonso, Sr., Claude Daubert, Sr.. Departement de Cardiologie CHU, Rennes, France
Journal: Journal of the American College of Cardiology (2001)
QuickStats: Percentage* of Adults Aged ≥20 Years Who Had Taken Any Dietary Supplement† in the Past 30 Days, by Sex and Family Income§ — National Health and Nutrition Examination Survey, United States, 2017–2018
Authors: Suruchi Mishra, Bryan Stierman, Jaime Gahche, Nancy Potischman
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Abbreviation: FPL = federal poverty level.* Error bars indicate 95% confidence intervals.† Dietary supplements are products taken by mouth that contain one or more dietary ingredients (vitamins, minerals, herbs or other botanicals, amino acids, and other substances) or their constituents and are labeled as such on the front panel.§ Family income is defined as a percentage of the FPL.Participants missing information regarding family income were included in the total estimates but excluded in the estimates by family income.During 2017-2018, 57.6% of adults aged ≥20 years had taken a dietary supplement within the past 30 days.The percentage increased with family income: 44.9% among those with family incomes <130% of the FPL, 56.2% among those with family incomes 130%-349% of the FPL, and 65.7% among those with family incomes ≥350% of the FPL.The increase with family income was seen for both men and women.Women were more likely than were men to use a dietary supplement overall (63.8% versus 50.8%) and at each income level.
Transition of the tumor microenvironment with clonal evolution of hepatocellular carcinoma.
Authors: Hiroaki Kanzaki, Sadahisa Ogasawara, Takafumi Sakuma, Naoto Fujita, Ryuta Kojima, Keisuke Koroki, Kazufumi Kobayashi, Masato Nakamura, Naoya Kanogawa, Soichiro Kiyono, Takayuki Kondo, Tomoko Saito, Ryo Nakagawa, Shingo Nakamoto, Ryosuke Muroyama, Tetsuhiro Chiba, Junichiro Ikeda, Masayuki Ohtsuka, Naoya Kato
Journal: Journal of Clinical Oncology (2022)

467 Background: The combination of atezolizumab and bevacizumab has become a standard treatment for advanced hepatocellular carcinoma (HCC). The indications for combination immunotherapy, including adjuvant therapy and combination with local therapy, are expected to expand in the future. Although exploring the tumor microenvironment has essential clinical implications in the era of combination immunotherapy, most studies on the tumor microenvironment in HCC are based on the analysis of archival samples at the time of HCC diagnosis. Considering the lengthy clinical course and characteristics of multicentric carcinogenesis, the tumor microenvironment may not be constant, but may differ from that at the time of advanced HCC. The present study aimed to assess the changes in the tumor microenvironment during the evolution to advanced HCC using archival samples and samples obtained prior to systemic therapy from the same patients. Methods: The tumor microenvironment was compared in 20 cases by immunohistochemical analyses of CD8, PD-L1, and VEGF expression. Levels of CD8-positive lymphocytes were defined as the mean number of CD8-positive lymphocytes in the tumor per 1 mm 2 and classified as low or high infiltration using the median value. PD-L1 expression was classified as negative (&lt; 1%) or positive (≥1%). VEGF expression was classified as low (&lt; 50%) or high (≥50%). Of the 20 cases, gene expression analysis was performed by the PanCancer IO360 Panel in 14 cases. Results: Approximately 40% of the archived samples were obtained at the early stage. Comparison of the tumor microenvironment between the two time points showed that 35% of the patients changed to CD8-positive lymphocyte high infiltration, 20% to positive PD-L1 expression, and 29% to high VEGF expression. The result of comparing gene profile was different between the archival samples and those prior to systemic therapy in 64% of the patients on the expression heat map. Gene set enrichment analysis showed significant changes in T cell cytotoxicity between the two time points. Conclusions: The tumor microenvironment might not be constant, but may change during the evolution to advanced HCC. In the present study, based on the results of the gene mutation analysis using whole-exome sequencing, we also reported the analyses by carcinogenic patterns such as multicentric occurrence and intrahepatic metastasis.
Entropy
Authors: Jason David Eubanks
Journal: Annals of Internal Medicine (2002)

Ad Libitum7 May 2002EntropyJason David EubanksJason David EubanksWilloughby Hills, OH 44094Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-9-200205070-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail He sits in his bedWith his back bent like a limp bananaOver his basketball bellyAs he spits and sputters his historyOf smoking, uncontrolled HTN, and AFibThrough the gaps in his crooked, yellowed teethWhile I try to focus on his bleary eyesHiding beneath a gnarled massOf uncombed hair—Arrhythmic.From the outside straight intoEven that bastion of chronicity,The cockswain's sinus calls drownIn the voices of a raucous, atrial crowd—And so it begins for me, physician in training,Whether with words, drugs, blades or electricity,To strap leashes around entropy. Author, Article, and Disclosure InformationAffiliations: Willoughby Hills, OH 44094Current Author Address: Jason David Eubanks, 36901 Beech Hills Drive, Willoughby Hills, OH 44094. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 May 2002Volume 136, Issue 9Page: 707KeywordsDrugs ePublished: 7 May 2002 Issue Published: 7 May 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Random thoughts on randomization
Authors: S. Vaisrub
Journal: JAMA (1978)

In their informative assessment of 13 years of aortocoronary bypass surgery, DeBakey and Lawrie (p 837), dispute the necessity of prospective randomized studies for the evaluation of surgical diagnostic and therapeutic techniques. They point out that certain time-honored criteria, particularly clinical experience, have proved reliable in assessing therapeutic value. They state, "The insistence on prospective randomized studies reflects a naive obsession with this research tool." In support of their statement, DeBakey and Lawrie could easily invoke the testimony of the past. Many great advances in medicine have been made without the benefit of controlled trials. The latter, in fact, is a mixed blessing. One shudders, for instance, to think what might have become of insulin had a controlled prospective trial reported a few deaths from hypoglycemic shock when this complication was unknown. Insulin might have been declared too toxic for human use. One also wonders about the number of fatalities
Two Case Reports by Richard Bright
Journal: JAMA (1967)

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
Tennis-shoe traction
Authors: R. A. Gatter
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Excellent, well-selected, and very apropos are the reprints of classics in art that you are using on the front covers of<i>JAMA</i>. I look forward to them, learn from them, and now have one framed and hanging in my den. Keep up the good work!
Inorganic Quantitative Analysis.
Journal: JAMA (1926)

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
A Pandemic Era
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2021)

A little over a year ago the word pandemic was, for most people, associated with disaster movies and history books. Despite repeated warnings about the very real risk of occurrence from infectious disease experts, it felt remote and distant, not something for most people to worry about day to day. Needless to say, that experience has now been transformed almost everywhere. As we move into 2021 and vaccine roll out scales up, many will be hoping that we can put the COVID-19 pandemic behind us. However, even if we manage a speedy recovery, we need to know if COVID was an unavoidable low probability risk—a once in a century event—or if it is an expression of an underlying trend that requires more self-reflection and capacity for change.
Clonal hematopoiesis in sickle cell disease
Authors: L. Alexander Liggett, Liam D. Cato, Joshua S. Weinstock, Yingze Zhang, S. Mehdi Nouraie, Mark T. Gladwin, Melanie E. Garrett, Allison Ashley-Koch, Marilyn J. Telen, Brian Custer, Shannon Kelly, Carla L. Dinardo, Ester C. Sabino, Paula Loureiro, Anna B. Carneiro-Proietti, Cláudia Maximo, Alexander P. Reiner, Gonçalo R. Abecasis, David A. Williams, Pradeep Natarajan, Alexander G. Bick, Vijay G. Sankaran
Journal: Journal of Clinical Investigation (2022)

BACKGROUNDCurative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. The occurrence of myeloid malignancies in these trials has prompted safety concerns. Individuals with SCD are predisposed to myeloid malignancies, but the underlying causes remain undefined. Clonal hematopoiesis (CH) is a premalignant condition that also confers significant predisposition to myeloid cancers. While it has been speculated that CH may play a role in SCD-associated cancer predisposition, limited data addressing this issue have been reported.METHODSHere, we leveraged 74,190 whole-genome sequences to robustly study CH in SCD. Somatic mutation calling methods were used to assess CH in all samples and comparisons between individuals with and without SCD were performed.RESULTSWhile we had sufficient power to detect a greater than 2-fold increased rate of CH, we found no detectable variation in rate or clone properties between individuals affected by SCD and controls. The rate of CH in individuals with SCD was unaltered by hydroxyurea use.CONCLUSIONSWe did not observe an increased risk for acquiring detectable CH in SCD, at least as measured by whole-genome sequencing. These results should help guide ongoing efforts and further studies that seek to better define the risk factors underlying myeloid malignancy predisposition in SCD and help ensure that curative therapies can be more safely applied.FUNDINGNew York Stem Cell Foundation and the NIH.
Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation
Authors: Gaoyu Liu, Yingying Chen, Ying Wang, Xiaohui Deng, Qiang Xiao, Lijuan Zhang, Haixu Xu, Xu Han, Aihua Lei, Juan He, Xing Li, Yingjiao Cao, Pan Zhou, Chunhui He, Peiqiong Wu, Wenhui Jiang, Meizheng Tan, Chun Chen, Quan Yang, Liwei Lu, Kai Deng, Zhi Yao, Jie Zhou
Journal: The Journal of Experimental Medicine (2022)

Group 2 innate lymphoid cells (ILC2s) have emerged as critical mediators in driving allergic airway inflammation. Here, we identified angiotensin (Ang) II as a positive regulator of ILC2s. ILC2s expressed higher levels of the Ang II receptor AT1a, and colocalized with lung epithelial cells expressing angiotensinogen. Administration of Ang II significantly enhanced ILC2 responses both in vivo and in vitro, which were almost completely abrogated in AT1a-deficient mice. Deletion of AT1a or pharmacological inhibition of the Ang II–AT1 axis resulted in a remarkable remission of airway inflammation. The regulation of ILC2s by Ang II was cell intrinsic and dependent on interleukin (IL)-33, and was associated with marked changes in transcriptional profiling and up-regulation of ERK1/2 phosphorylation. Furthermore, higher levels of plasma Ang II correlated positively with the abundance of circulating ILC2s as well as disease severity in asthmatic patients. These observations reveal a critical role for Ang II in regulating ILC2 responses and airway inflammation.
CD116+ fetal precursors migrate to the perinatal lung and give rise to human alveolar macrophages
Authors: Elza Evren, Emma Ringqvist, Jean-Marc Doisne, Anna Thaller, Natalie Sleiers, Richard A. Flavell, James P. Di Santo, Tim Willinger
Journal: The Journal of Experimental Medicine (2022)

Despite their importance in lung health and disease, it remains unknown how human alveolar macrophages develop early in life. Here we define the ontogeny of human alveolar macrophages from embryonic progenitors in vivo, using a humanized mouse model expressing human cytokines (MISTRG mice). We identified alveolar macrophage progenitors in human fetal liver that expressed the GM-CSF receptor CD116 and the transcription factor MYB. Transplantation experiments in MISTRG mice established a precursor–product relationship between CD34−CD116+ fetal liver cells and human alveolar macrophages in vivo. Moreover, we discovered circulating CD116+CD64−CD115+ macrophage precursors that migrated from the liver to the lung. Similar precursors were present in human fetal lung and expressed the chemokine receptor CX3CR1. Fetal CD116+CD64− macrophage precursors had a proliferative gene signature, outcompeted adult precursors in occupying the perinatal alveolar niche, and developed into functional alveolar macrophages. The discovery of the fetal alveolar macrophage progenitor advances our understanding of human macrophage origin and ontogeny.
Errors in Flow Diagram
Authors: Michael Barry, Karina Davidson, Carol Mangione
Journal: JAMA (2021)

Erick Forno, MD, MPH; Leonard B. Bacharier, MD; Wanda Phipatanakul, MD, MS; Theresa W. Guilbert, MD, MS; Michael D. Cabana, MD, MPH; Kristie Ross, MD, MS; Ronina Covar, MD; James E. Gern, MD; Franziska J. Rosser, MD, MPH; Joshua Blatter, MD, MPH; Sandy Durrani, MD; Yueh-Ying Han, PhD; Stephen R. Wisniewski, PhD; Juan C. Celedón, MD, DrPH
The Public Service
Journal: JAMA (1906)

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
A common variant of the AMPD1 gene predicts improved survival in patients with ischemic cardiomyopathy, but not non-ischemic cardiomyopathy Yoshikazu Yazaki, Siavash Ghaffari, Joseph B. Muhlestein, Noal I. Hart, Tami L. Bair, Benjamin D. Horne, Dale G. Renlund, Jeffrey L. Anderson, John F. Carlquist. LDS Hospital, Salt Lake City, UT, University of Utah, Salt Lake City, UT
Journal: Journal of the American College of Cardiology (2001)