tbuckley/cabot-search huggingface dataset:
Abstract 446: Activation of γ2-ampk Suppresses Ribosome Biogenesis and Protects Against Myocardial Ischemia-reperfusion Injury
Authors: Yang Cao, Naveen Bojjireddy, Maengjo Kim, Tao Li, Peiyong Zhai, Narayani Nagarajan, Junichi Sadoshima, Rong Tian
Journal: Circulation Research (2017)

AMP-activated protein kinase (AMPK) is a heterotrimeric protein that senses cellular energy status and maintains energy homeostasis by switching off biosynthetic pathways and increasing catabolism. The subcellular localization of AMPK has been shown to affect its activation and function. The γ2 subunit has both nuclear localization sequence and nuclear export sequence suggesting that it can shuttle between the two compartments. By overexpressing GFP-tagged γ subunits in COS7 cells followed by glucose deprivation or AMPK activation (A769662), we demonstrated that AMPK containing γ2 but not γ1 or γ3 subunit translocates into nucleus. Nuclear accumulation of AMPK complexes containing γ2-subunit phosphorylates and inactivates Pol I-associated transcription factor TIF-IA at Ser-635, precluding the assembly of transcription initiation complexes and lowering preribosomal RNA (pre-rRNA) level. Down-regulation of rRNA synthesis attenuated expression of ER stress markers (spliced X-box binding protein-1 and C/EBP homologous protein) and ER stress-induced cell death. Deleting γ2-AMPK using CRISPR-Cas9 system led to increases in pre-rRNA level, ER stress markers and cell death during glucose deprivation. To study the function of γ2-AMPK in the heart, we generated a mouse model with cardiac specific deletion of γ2-AMPK (cKO). Although the total AMPK activity was unaltered in cKO hearts due to upregulation of γ1-AMPK the lack of γ2-AMPK sensitizes the heart to myocardial ischemia-reperfusion (I/R, 30min ischemia followed by 24hr reperfusion) injury as evidenced by larger infarct size (Infarct size/area at risk: 34.7±5.7% vs. 50.6±8.9%, for control and cKO respectively, P&lt;0.05). The cKO failed to suppress pre-rRNA level during I/R and showed higher levels of ER stress markers. Conversely, cardiac-specific overexpression (OE) of γ2-AMPK decreased ER stress markers and pre-rRNA level upon I/R injury and the infarct size was reduced (Infarct size/area at risk: 26.8±6.5% for control vs. 15.8±3.7% for OE, P&lt;0.05), suggesting that γ2-AMPK protects against I/R injury and ER stress in the heart. Taken together, our study reveals isoform-specific functions of γ2-AMPK in modulating protein synthesis, cell survival and cardioprotection.
Anatomy
Journal: JAMA (1999)

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
Is the remodeling pattern consistent throughout an atherosclerotic lesion? Intravascular ultrasound evidence of heterogeneity within a single diseased segment Atila Iyisoy, Khaled M. Ziada, Mohammed Balghith, Allen Jeremias, Hiroshi Tsutsui, Samir R. Kapadia, Paul Schoenhagen, Mandish Rai, Steven E. Nissen, E. Murat Tuzcu. Cleveland Clinic foundation, Cleveland, OH
Journal: Journal of the American College of Cardiology (2001)
Alzheimers Disease &amp; Dementia
Journal: Alzheimers Disease & Dementia (2021)

Scholars.Direct is an open access publisher hosting high quality peer-reviewed journals including broad interest titles in multidisciplinary aspects of science, medicine and technology. Each journal has the in-house and external review experts' team providing support and guidance to researchers/scholars to improvise the submitted papers, however the final decision will be with editors. Scholars.Direct provide services of gold open access and double blind peer review system to assure the scientific standards of published content.
Preparing a child for a good-bye visit to a dying loved one
Authors: J. S. Rubenstein
Journal: JAMA (1982)

DEATH is never easy to explain to children, particularly younger ones. Experts may compound the problem by giving parents vague generalizations, such as "explain death honestly to the child," without suggesting specific phrases to use. The parents still remain at a loss for words and may feel even worse than they did before they received the advice, because now they think they should know what to say. Preparing a child for a "good-bye" visit to a dying loved one is an aspect of death that probably has received the least attention. It is not customary, in the United States, to take a child on such a visit. The epitome of this exclusion may be found in "Gone With the Wind": when Melanie is dying, all of the most meaningful people in her life get to say good-bye to her, except her child. When my father-in-law was dying of cancer, my
The So-Called "Cerebral Palsy" Program
Journal: JAMA (1949)

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
Passive immunization against phosphorylated tau improves features of Huntington's disease pathology
Authors: Melanie Alpaugh, Maria Masnata, Aurelie de Rus Jacquet, Eva Lepinay, Hélèna L. Denis, Martine Saint-Pierre, Peter Davies, Emmanuel Planel, Francesca Cicchetti
Journal: Molecular Therapy (2022)

Huntington's disease is classically described as a neurodegenerative disorder of monogenic aetiology. The disease is characterized by an abnormal polyglutamine expansion in the huntingtin gene, which drives the toxicity of the mutated form of the protein. However, accumulation of the microtubule-associated protein tau, which is involved in a number of neurological disorders, has also been observed in patients with Huntington's disease. In order to unravel the contribution of tau hyperphosphorylation to hallmark features of Huntington's disease, we administered weekly intraperitoneal injections of the anti-tau pS202 CP13 monoclonal antibody to zQ175 mice and characterized the resulting behavioral and biochemical changes. After 12 weeks of treatment, motor impairments, cognitive performance and general health were improved in zQ175 mice along with a significant reduction in hippocampal pS202 tau levels. Despite the lack of effect of CP13 on neuronal markers associated with Huntington's disease pathology, tau-targeting enzymes and gliosis, CP13 was shown to directly impact mutant huntingtin aggregation such that brain levels of amyloid fibrils and huntingtin oligomers were decreased, while larger huntingtin protein aggregates were increased. Investigation of CP13 treatment of Huntington's disease patient-derived induced pluripotent stem cells (iPSCs) revealed a reduction in pS202 levels in differentiated cortical neurons and a rescue of neurite length. Collectively, these findings suggest that attenuating tau pathology could mitigate behavioral and molecular hallmarks associated with Huntington's disease.
Reply
Authors: Alejandro Macchia, Hugo Grancelli, Sergio Varini, Daniel Nul, Nicolás Laffaye, Javier Mariani, Daniel Ferrante, Raúl Badra, Julio Figal, Silvina Ramos, Gianni Tognoni, Hernán C. Doval
Journal: Journal of the American College of Cardiology (2013)
Clarification of Role of Funder Statement
Journal: JAMA Network Open (2021)

Hana Kahleova, MD, PhD; Kitt Falk Petersen, MD; Gerald I. Shulman, MD, PhD; Jihad Alwarith, BS; Emilie Rembert, BS; Andrea Tura, PhD; Martin Hill, PhD; Richard Holubkov, PhD; Neal D. Barnard, MD
Management of Chronic Low Back Pain
Authors: Kenneth R. Cohen
Journal: JAMA Internal Medicine (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 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
Incorrect Year
Journal: JAMA (1984)

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
Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination
Authors: Samuel M. S. Cheng, Chris Ka Pun Mok, Yonna W. Y. Leung, Susanna S. Ng, Karl C. K. Chan, Fanny W. Ko, Chunke Chen, Karen Yiu, Bosco H. S. Lam, Eric H. Y. Lau, Ken K. P. Chan, Leo L. H. Luk, John K. C. Li, Leo C. H. Tsang, Leo L. M. Poon, David S. C. Hui, Malik Peiris
Journal: Nature Medicine (2022)
Growing pains.
Authors: E Ftew, E Caspary, R Smhephme, A Brown, Mr Peter, G Davies
Journal: BMJ (1972)

and immunotherapy (an attempt to assist natural defence) will be inst,tuted without necessarily predicting the site and nature of the malignant growth.Further work in this laboratory has not induced us to relinquish our tentative con- clusion' that there may well be a common antigen appearing in all human malignant neoplasms.If this is indeed so we may be optimistic that an effective treatment of cancer (whatever its primary cause(s) may be) is a problem essentially soluble with methodology already developed.-Weare, etc.,
Randomized phase II trial of postoperative adjuvant capecitabine and temozolomide versus observation in high-risk pancreatic neuroendocrine tumors: SWOG S2104.
Authors: Heloisa P. Soares, Katherine A Guthrie, Syed A. Ahmad, Mary Kay Washington, Brian Hemendra Ramnaraign, Nitya Prabhakar Raj, Carole Seigel, Shay Bellasea, E. Gabriela Chiorean, Arvind Dasari, Jonathan R. Strosberg, Cathy Eng, Philip Agop Philip
Journal: Journal of Clinical Oncology (2022)

TPS515 Background: Pancreatic neuroendocrine tumors (pNETS) account for about 1-2% of all the pancreas tumors for which resection is the only curative intent modality, however, despite surgery, many patients will experience recurrence. Tumor size, positive lymph nodes and higher grade are prognostic factors for recurrence. The U.S. Neuroendocrine Tumor Study Group published a predictive score (Zaidi score, see table) demonstrating that tumors with a score≥6 had a 33% likelihood of recurrence by 24 months. Furthermore, it is known that that patients with metastatic disease who undergo curative intent resection also have a great risk of recurrence. Despite these known risk factors for recurrence, to date, no prospective study exploring the role of adjuvant cytotoxic chemotherapy has ever been performed in this population. Supported by the E2211 results using capecitabine and temozolomide (CAPTEM) in the metastatic setting, S2104 investigates the role of CAPTEM in the adjuvant setting. Methods: S2104 is a randomized phase II trial designed to evaluate recurrence-free survival (RFS) in participants with resected pNETs randomized on a 2:1 fashion to CAPTEM or observation. Patient are eligible if they had resected well-differentiated grade 2 or 3 (ki-67 up to 55%) pNETS with a Zaidi score of ≥ 3. Patients may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection. Key eligibility criteria: age ≥18 years, Zubrod performance status of 0-2, adequate organ and marrow function. Stratification factors include 1) Disease status prior to resection (metastatic vs. non-metastatic disease) and 2) Zaidi score (≥ 6 vs. &lt; 6). Participants will be followed with imaging for 5 years. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180821, U10CA180868. Clinical trial information: NCT05040360. [Table: see text]
Phase 2 study of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, with gemcitabine/nab-paclitaxel (GnP) in first-line advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Devalingam Mahalingam, Benedito A. Carneiro, Howard Safran, Steven Francis Powell, Andrew L. Coveler, Elizabeth J. Davis, Andres Cervantes, Vaibhav Sahai, Neeltje Steeghs, Marisol Huerta, Jordan Berlin, Mary Frances Mulcahy, Francis J. Giles, Ludimila Cavalcante, Anwaar Saeed
Journal: Journal of Clinical Oncology (2022)

578 Background: GSK-3β overexpression is associated with worse prognosis and chemotherapy resistance in PDAC. GSK-3β inhibition reverses chemotherapy-resistance by inhibiting chemotherapy-induced, ATR-mediated, DNA damage response. 9-ING-41 has significant anti-tumor activity through apoptosis induction, anti-fibrotic activity and NK/T-cell effector stimulation. We hypothesized that 9-ING-41 in combination with GnP chemotherapy would lead to anti-tumor activity, with improved tumor responses in patients with advanced PDAC in the first line setting. Methods: Primary endpoint is disease control rate (DCR). DCR = confirmed complete response (CR), partial response (PR), or stable disease (SD) ≥ 16 weeks (wks). Secondary endpoints are safety and ORR (overall response rates). Eligibility: Advanced PDAC, ECOG PS 0-2, no prior therapy in the metastatic setting and no systemic therapy in prior 6 months. Pts received 9-ING-41 15mg/kg IV twice-weekly with G 1,000 mg/m 2 and nP 125 mg/m 2 on days 1,8,15 of a 28-day cycle. Simon 2-Stage Design for DCR of 65% and null hypothesis of 50% (historical control), 80% power and 2 sided-significance level of.05. Up to 23 fully evaluable pts planned for stage 1 and if ≥ 12 evaluable patients achieve a DCR 37 additional pts will be enrolled on a second stage or a randomized study commenced. Results: As of Sept 27, 2021, 42 pts enrolled. Median age: 67. 24 females, 18 males. 38 pts with metastatic and 4 with locally advanced disease. Prior adjuvant therapy: 4 pts each FOLFIRINOX and gemcitabine-based. No 9-ING-41-attributable SAEs to date. 9-ING-41 attributed AEs: visual disturbance: 24 (75%) G1/2, 1 (3%) G3; infusion reactions 9 (28%) G1/2. Chemotherapy-related AEs: anemia 13 (40%) G1/2, 1 (3%) G3; neutropenia 2 (6%) G1/2, 13 (40%) G3/4; thrombocytopenia 9 (28%) G1/2, 2 (6%) G3/4; diarrhea 8 (25%) G1/2, 4 (13%) G3; fatigue 9 (28%) G1/2, 3 (9%) G3; nausea/vomiting 24 (75%) G1/2, 1 (3%) G3; constipation 9 (28%) G1/2; febrile neutropenia 5 (16%) G3/4. In 21 pts currently evaluable for response, DCR was 62% and ORR 43%. There were 2 confirmed CRs, 6 confirmed and 1 unconfirmed PRs, 4 SD and 8 disease progressions were observed. Amongst responder’s median duration of response has not yet been reached. Conclusions: 9-ING-41 plus GnP demonstrated encouraging clinical activity but chemotherapy-related AEs were significant. Based on efficacy data to date, including confirmed CRs, we have commenced a randomized phase 2 study, evaluating 9-ING-41 plus GnP vs Gn P alone. Enrollment to the randomized study is now open (NCT03678883). Clinical trial information: NCT03678883.
Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow
Authors: Chenglong Xie, Xu-Xu Zhuang, Zhangming Niu, Ruixue Ai, Sofie Lautrup, Shuangjia Zheng, Yinghui Jiang, Ruiyu Han, Tanima Sen Gupta, Shuqin Cao, Maria Jose Lagartos-Donate, Cui-Zan Cai, Li-Ming Xie, Domenica Caponio, Wen-Wen Wang, Tomas Schmauck-Medina, Jianying Zhang, He-ling Wang, Guofeng Lou, Xianglu Xiao, Wenhua Zheng, Konstantinos Palikaras, Guang Yang, Kim A. Caldwell, Guy A. Caldwell, Han-Ming Shen, Hilde Nilsen, Jia-Hong Lu, Evandro F. Fang
Journal: Nature Biomedical Engineering (2022)

Abstract A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals’ memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational–experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.
<i>COVID-19 Stats:</i> COVID-19 Incidence,* by Urban-Rural Classification<sup>†</sup> — United States, January 22–October 31, 2020<sup>§</sup>
Authors: Lindsey Duca, Jayme Coyle, Carter Mccabe, Catherine Mclean
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Large fringe metro
Family Medicine
Authors: Thomas L. Schwenk
Journal: JAMA (1992)

The specialty of family practice continues to change dramatically. Increased national emphasis on improving access to cost-effective health care services, and on teaching in the ambulatory setting, has increased the need for family physicians, as well as highlighted the importance of primary care research. The breadth and scope of family medicine is evident on review of recent clinical advances that directly affected clinical practice. Significant progress has been made in the management of most of the "top 20" diagnoses in family practice, which account for the medical complaints of half of a typical family physician's patients.<sup>1</sup>These developments have affected the care of patients with common clinical problems, health promotion and disease screening and prevention practices, and the provision of mental health care. The Agency for Health Care Policy and Research has disseminated clinical practice guidelines for incontinence and pain management.<sup>2</sup>While politically controversial, these guidelines have not
Error in Figure
Authors: Alan Davis, Roland Griffiths
Journal: JAMA Psychiatry (2021)

To the Editor On behalf of our coauthors, we regret to report that we have discovered calculation errors in some of the reported effects in our Original Investigation, "Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial," 1 that was published in JAMA Psychiatry on November 4, 2020.These calculation errors were detected when we began conducting analyses for a follow-up study.This resulted in a full reanalysis of all data in our study.During this process, we discovered an error in the response rate for the overall sample, which was marginally higher than reported (67% should have been 71%), and several errors in effect sizes and their confidence intervals.Importantly, the corrections for these errors do not affect the direction, significance, or interpretation of the results or our conclusions.Thus, we have requested that our article be corrected. 2In the main article, these include corrections to the Abstract Results, Results, and Figure captions.In the Supplement, there are corrections to eTables and eFigures.We sincerely regret that these errors occurred.We have conducted a careful rereview of the entire article text and analyses and we confirm that no other errors have been identified.
Gender Disparities Among Highly Cited Researchers in Biomedicine, 2014-2020
Authors: Amrollah Shamsi, Brady Lund, Mohammad Javad Mansourzadeh
Journal: JAMA Network Open (2022)

gender disparities among researchers are not easy to overcome, increasing the number of women in prestigious biomedical research positions may boost both their research productivity and their likelihood of publishing highly cited publications.Our study has some limitations.Some fields did not fit precisely or entirely within the category of biomedicine (such as psychology and psychiatry).However, there was no good way to divide these publications.Because the methodology for Clarivate's listing of HCRs has changed since its inception in 2001, only recent HCR lists with the same methodology were used.