tbuckley/cabot-search huggingface dataset:
Nurse-Practitioner: Reprise
Journal: JAMA (1970)

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
Suppression of Fli-1 protects against pericyte loss and cognitive deficits in Alzheimer's disease
Authors: Pengfei Li, Yan Wu, Eric D. Hamlett, Andrew J. Goodwin, Perry V. Halushka, Steven L. Carroll, Meng Liu, Hongkuan Fan
Journal: Molecular Therapy (2022)

Brain pericytes regulate cerebral blood flow, maintain the integrity of the blood-brain barrier (BBB), and facilitate the removal of amyloid β (Aβ), which is critical to healthy brain activity. Pericyte loss has been observed in brains from patients with Alzheimer's disease (AD) and animal models. Our previous data demonstrated that friend leukemia virus integration 1 (Fli-1), an erythroblast transformation-specific (ETS) transcription factor, governs pericyte viability in murine sepsis; however, the role of Fli-1 and its impact on pericyte loss in AD remain unknown. Here, we demonstrated that Fli-1 expression was up-regulated in postmortem brains from a cohort of human AD donors and in 5xFAD mice, which corresponded with a decreased pericyte number, elevated inflammatory mediators, and increased Aβ accumulation compared with cognitively normal individuals and wild-type (WT) mice. Antisense oligonucleotide Fli-1 Gapmer administered via intrahippocampal injection decelerated pericyte loss, decreased inflammatory response, ameliorated cognitive deficits, improved BBB dysfunction, and reduced Aβ deposition in 5xFAD mice. Fli-1 Gapmer-mediated inhibition of Fli-1 protected against Aβ accumulation-induced human brain pericyte apoptosis in vitro. Overall, these studies indicate that Fli-1 contributes to pericyte loss, inflammatory response, Aβ deposition, vascular dysfunction, and cognitive decline, and suggest that inhibition of Fli-1 may represent novel therapeutic strategies for AD.
Changing epidemiology of esophageal cancer: A population-based study over 43 years (1975–2018).
Authors: Jeffrey Bien, Theresa Hoang-Anh Nguyen, Mayada Aljehani, Jerry S.H. Lee, David H. Wang, Albert Y. Lin
Journal: Journal of Clinical Oncology (2022)

247 Background: Esophageal cancer (EC) is the seventh most common cancer worldwide. Previous studies have indicated that the incidence of squamous cell carcinoma of the esophagus (SCE) in the US has declined since the 1970s. In comparison, the incidence of adenocarcinoma of the esophagus (ACE) has sharply risen in the US since the 1970s. This study aimed to examine temporal trends in incidence rates of EC, ACE, and SCE that include recent decades. Methods: Data were derived from the Surveillance, Epidemiology, and End Results (SEER) of the National Cancer Institute - a population-based cancer database. Using SEER*Stat, we calculated the age-adjusted incidence rates (AAIR) for EC, ACE, and SCE in both SEER 9 (for longest follow-up time) and SEER 21 (the largest cohort covering 36.7% of the US population). Temporal incidence trends were examined using Joinpoint analyses to estimate the annual percent change (APC). Subgroup analyses were performed for sex, age, and race/ethnicity. Results: See Table. When stratified by age, age &lt;64 years had a significant decrease in incidence with an APC of -1.1 (2007-2018), while the incidence plateaued in the remaining age groups. The rise in incidence was highest among non-Hispanic whites (NHW) from 2000-2004 (APC 4.0), especially NHW males (APC 3.0); however, the incidence plateaued in all race/ethnicity groups after 2006. Conclusions: The AAIR of EC as a whole has been decreasing since 2004. The AAIR of ACE has, for the first time, plateaued in the most recent decade (2006-2018), after having risen for three preceding decades (1975-2006); we find this effect is mainly driven by the AAIR from NHW males, age &lt;64 years. The incidence of SCE has continued to decline since 1975. Future studies should further explore the underlying etiology of these patterns.[Table: see text]
Current Comment
Journal: JAMA (1934)

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 collagen enhancer-promoter construct in transgenic mice is markedly stimulated by ethanol administration
Authors: C Walton
Journal: Hepatology (1996)

Type I collagen synthesis and deposition is generally indicative of irreversible damage in alcohol-induced cirrhosis in humans. However, in rodents, ethanol alone does not readily cause hepatic fibrosis. To determine whether this is because of a lack of ethanol-responsive elements, an artificial enhancer construct controlling rat type I collagen gene transcription was prepared in transgenic mice. The gene construct, ColCAT3.6, was a chimeric sequence containing the marker chloramphenicol acetyltransferase (CAT) gene linked to 3.5 kb of the rat α 1(I) 5′-flanking DNA, and 115 base pairs (bp) of transcribed collagen gene. Groups of transgenic mice were given 4 g/kg ethanol orally, twice daily for 4 weeks. As a positive control for hepatic fibrosis, transgenic mice were given intraperitoneal injections of CCl4, twice weekly for 4 weeks. Livers were assayed for CAT activity. Endogenous mouse collagen α 1(I) messenger RNA (mRNA) and transgene CAT mRNA were measured by RNase protection assays. Collagen synthesis in livers from the transgenic mice treated with ethanol were increased over controls, but the levels were not significantly different. Endogenous collagen α 1(I) steady-state mRNA levels in ethanol-treated mice were not significantly different compared with saline-treated controls. However, the transgene mRNA levels in ethanol-treated animals increased approximately 21-fold compared with saline-treated controls, as measured by RNase protection assays. Furthermore, the transgene product as measured by CAT activity in ethanol-treated mice was significantly increased threefold over saline-treated controls. We conclude that the 5′-flanking region of the rat α 1(I) collagen gene does contain regulatory elements that are strongly responsive to ethanol administration.
Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer’s disease
Authors: Alessandro Dario Confettura, Eleonora Cuboni, Mohamed Rafeet Ammar, Shaobo Jia, Guilherme M. Gomes, PingAn Yuanxiang, Rajeev Raman, Tingting Li, Katarzyna M. Grochowska, Robert Ahrends, Anna Karpova, Alexander Dityatev, Michael R. Kreutz
Journal: Translational Neurodegeneration (2022)

Abstract Background The metabolic syndrome is a consequence of modern lifestyle that causes synaptic insulin resistance and cognitive deficits and that in interaction with a high amyloid load is an important risk factor for Alzheimer's disease. It has been proposed that neuroinflammation might be an intervening variable, but the underlying mechanisms are currently unknown. Methods We utilized primary neurons to induce synaptic insulin resistance as well as a mouse model of high-risk aging that includes a high amyloid load, neuroinflammation, and diet-induced obesity to test hypotheses on underlying mechanisms. Results We found that neddylation and subsequent activation of cullin-RING ligase complexes induced synaptic insulin resistance through ubiquitylation and degradation of the insulin-receptor substrate IRS1 that organizes synaptic insulin signaling. Accordingly, inhibition of neddylation preserved synaptic insulin signaling and rescued memory deficits in mice with a high amyloid load, which were fed with a 'western diet'. Conclusions Collectively, the data suggest that neddylation and degradation of the insulin-receptor substrate is a nodal point that links high amyloid load, neuroinflammation, and synaptic insulin resistance to cognitive decline and impaired synaptic plasticity in high-risk aging.
Self-protection as an adaptive female strategy
Authors: Joyce F. Benenson, Christine E. Webb, Richard W. Wrangham
Journal: Behavioral and Brain Sciences (2021)

Many male traits are well explained by sexual selection theory as adaptations to mating competition and mate choice, whereas no unifying theory explains traits expressed more in females. Anne Campbell's "staying alive" theory proposed that human females produce stronger self-protective reactions than males to aggressive threats because self-protection tends to have higher fitness value for females than males. We examined whether Campbell's theory has more general applicability by considering whether human females respond with greater self-protectiveness than males to other threats beyond aggression. We searched the literature for physiological, behavioral, and emotional responses to major physical and social threats, and found consistent support for females' responding with greater self-protectiveness than males. Females mount stronger immune responses to many pathogens; experience a lower threshold to detect, and lesser tolerance of, pain; awaken more frequently at night; express greater concern about physically dangerous stimuli; exert more effort to avoid social conflicts; exhibit a personality style more focused on life's dangers; react to threats with greater fear, disgust, and sadness; and develop more threat-based clinical conditions than males. Our findings suggest that in relation to threat, human females have relatively heightened protective reactions compared to males. The pervasiveness of this result across multiple domains suggests that general mechanisms might exist underlying females' unique adaptations. An understanding of such processes would enhance knowledge of female health and well-being.
INTEGRATE IIb: A randomized phase III open label study of regorafenib + nivolumab versus standard chemotherapy in refractory advanced gastroesophageal cancer (AGOC).
Authors: Nick Pavlakis, Kohei Shitara, Katrin Marie Sjoquist, Andrew James Martin, Anthony Jaworski, Sonia Yip, Do-Youn Oh, Markus H. Moehler, Tanios S. Bekaii-Saab, John Simes, David Goldstein
Journal: Journal of Clinical Oncology (2022)

TPS366 Background: Advanced Gastro-oesophageal Carcinoma (AGOC) has a poor prognosis, and there is no established standard treatment following failure of first- and second-line chemotherapy. Regorafenib (BAY 73-4506) is an investigational oral multi-targeted tyrosine kinase inhibitor (TKI) which targets angiogenic (VEGF, TIE-2), stromal (PDGF-β), and oncogenic (RAF, RET and KIT) receptor tyrosine kinases, and has shown activity in this setting. Single agent regorafenib prolonged progression free survival (PFS) versus placebo across all regions/subgroups in the INTEGRATE randomised phase 2 trial. Current options in refractory AOGC involves sequencing through chemotherapy with the latest active agent approved being trifluridine/tipiracil, TAS-102. Promising activity in refractory AOGC has been seen with the combination of regorafenib &amp; nivolumab. INTEGRATE IIb–will compare the effectiveness of the combination of regorafenib &amp; nivolumab in pre-treated patients with AGOC to current standard chemotherapy. Methods: Randomised phase III, open label study with 2:1 randomisation (RegoNivo : standard chemotherapy) and stratification by: Geographic region (Asia vs. Rest of World); Prior VEGF inhibitors (Yes vs No); Prior immunotherapy (Yes vs No). RegoNivo arm will receive 90mg (3x30mg) of regorafenib days 1-21 of each 28-day treatment cycle with intravenous nivolumab 240 mg day 1 of each 14 day cycle until disease progression or prohibitive adverse events as per protocol. The control arm will receive the investigator’s choice of the following chemotherapy; a taxane (paclitaxel or docetaxel), irinotecan or oral trifluridine/tipiracil (TAS102). Primary endpoint: OS. Secondary endpoints: PFS, response rate, quality of life, toxicity, exploratory correlative biomarkers. Clinical trial information: NCT04879368.
A community challenge for a pancancer drug mechanism of action inference from perturbational profile data
Authors: Eugene F. Douglass, Robert J. Allaway, Bence Szalai, Wenyu Wang, Tingzhong Tian, Adrià Fernández-Torras, Ron Realubit, Charles Karan, Shuyu Zheng, Alberto Pessia, Ziaurrehman Tanoli, Mohieddin Jafari, Fangping Wan, Shuya Li, Yuanpeng Xiong, Miquel Duran-Frigola, Martino Bertoni, Pau Badia-i-Mompel, Lídia Mateo, Oriol Guitart-Pla, Verena Chung, Jing Tang, Jianyang Zeng, Patrick Aloy, Julio Saez-Rodriguez, Justin Guinney, Daniela S. Gerhard, Andrea Califano
Journal: Cell Reports Medicine (2022)

The Columbia Cancer Target Discovery and Development (CTD2) Center is developing PANACEA, a resource comprising dose-responses and RNA sequencing (RNA-seq) profiles of 25 cell lines perturbed with ∼400 clinical oncology drugs, to study a tumor-specific drug mechanism of action. Here, this resource serves as the basis for a DREAM Challenge assessing the accuracy and sensitivity of computational algorithms for de novo drug polypharmacology predictions. Dose-response and perturbational profiles for 32 kinase inhibitors are provided to 21 teams who are blind to the identity of the compounds. The teams are asked to predict high-affinity binding targets of each compound among ∼1,300 targets cataloged in DrugBank. The best performing methods leverage gene expression profile similarity analysis as well as deep-learning methodologies trained on individual datasets. This study lays the foundation for future integrative analyses of pharmacogenomic data, reconciliation of polypharmacology effects in different tumor contexts, and insights into network-based assessments of drug mechanisms of action.
Diuretics and antihypertensives
Authors: G. A. Perera
Journal: JAMA (1966)

Diuretic and antihypertensive drugs are used extensively and the untoward reactions they produce extend over the entire spectrum of drug effects. But the problem is compounded and confounded further by a common denominator that must be in the forefront of the physician's mind on all occasions, namely, that the beneficial action of these drugs is accomplished principally by hurting rather than helping, frequently at sites already damaged by the diseases under treatment. This statement calls for explanation. Diuretics act on the kidneys to increase the urinary output. They are effective, not by correcting an abnormal state, but by interfering with or blocking the normal mechanisms involved in renal tubular reabsorption. With many edematous states—such as those seen in congestive failure, in cirrhosis with its attendant secondary hyperaldosteronism, in nephritis, in nephrosis—the function of the kidneys already is damaged or deranged. The majority of antihypertensive drugs act through parts of the
The effect of early post-infarction mitral regurgitation on late ventricular remodeling Robert C. Gorman, Joseph H. Gorman, III, Benjamin M. Jackson, T. Sloane Guy, IV, Sina L. Moainie, Theodore Plappert, Martin St.John-Sutton, L. Henry Edmunds, Jr.. University of Pennsylvania School of Medicine, Philadelphia, PA
Journal: Journal of the American College of Cardiology (2001)
Burkitt Lymphoma International Prognostic Index
Authors: Adam J. Olszewski, Lasse H. Jakobsen, Graham P. Collins, Kate Cwynarski, Veronika Bachanova, Kristie A. Blum, Kirsten M. Boughan, Mark Bower, Alessia Dalla Pria, Alexey Danilov, Kevin A. David, Catherine Diefenbach, Fredrik Ellin, Narendranath Epperla, Umar Farooq, Tatyana A. Feldman, Alina S. Gerrie, Deepa Jagadeesh, Manali Kamdar, Reem Karmali, Shireen Kassam, Vaishalee P. Kenkre, Nadia Khan, Seo-Hyun Kim, Andreas K. Klein, Izidore S. Lossos, Matthew A. Lunning, Peter Martin, Nicolas Martinez-Calle, Silvia Montoto, Seema Naik, Neil Palmisiano, David Peace, Elizabeth H. Phillips, Tycel J. Phillips, Craig A. Portell, Nishitha Reddy, Anna Santarsieri, Maryam Sarraf Yazdy, Knut B. Smeland, Scott E. Smith, Stephen D. Smith, Suchitra Sundaram, Adam S. Zayac, Xiao-Yin Zhang, Catherine Zhu, Chan Y. Cheah, Tarec C. El-Galaly, Andrew M. Evens
Journal: Journal of Clinical Oncology (2021)

Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches.We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019.In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively.The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.
Sense of agency for intracortical brain–machine interfaces
Authors: Andrea Serino, Marcia Bockbrader, Tommaso Bertoni, Sam Colachis IV, Marco Solcà, Collin Dunlap, Kaitie Eipel, Patrick Ganzer, Nick Annetta, Gaurav Sharma, Pavo Orepic, David Friedenberg, Per Sederberg, Nathan Faivre, Ali Rezai, Olaf Blanke
Journal: Nature Human Behaviour (2022)
Impact of serum sex hormones on severe ischaemia in postmenopausal women with chronic coronary artery disease Ayse Emre, Mehmet Yazicioglu, Metin Gursurer, Yasemin Yakut, Birsen Ersek. Siyami Ersek Thoracic&amp;CV Surgery Center, Istanbul, Turkey, Zeynep Kamil Maternity Hospital, Istanbul, Turkey
Journal: Journal of the American College of Cardiology (2001)
Liability for transfusion-acquired disease
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The recent update by Rabkin and Rabkin<sup>1</sup>on individual and institutional liability for transfusion-acquired diseases is a welcome communication to clinicians who routinely administer blood products. I am concerned that the review may not completely reflect the current legal status of transfusion in New Hampshire, however. In 1971, the New Hampshire legislature passed a law (Strict Liability and Implied Warranties Limited, NH RSA 507:8-b) eliminating the concept of strict liability in tort and implied warranty in relation to the procurement, furnishing, donation, processing, distributing, or use of blood products. The statute specifically states that individuals or corporations are not liable for damages except those caused by negligence. This statute was still in effect as recently as the 1985 cumulative supplement. It is important for physicians practicing in New Hampshire to be aware that interpretation of §402A of the Restatement of Torts, Second, and the application of
Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication
Authors: Johanna Theruvath, Marie Menard, Benjamin A. H. Smith, Miles H. Linde, Garry L. Coles, Guillermo Nicolas Dalton, Wei Wu, Louise Kiru, Alberto Delaidelli, Elena Sotillo, John L. Silberstein, Anna C. Geraghty, Allison Banuelos, Molly Thomas Radosevich, Shaurya Dhingra, Sabine Heitzeneder, Aidan Tousley, John Lattin, Peng Xu, Jing Huang, Nicole Nasholm, Andy He, Tracy C. Kuo, Emma R. B. Sangalang, Jaume Pons, Amira Barkal, Rachel E. Brewer, Kristopher D. Marjon, Jose G. Vilches-Moure, Payton L. Marshall, Ricardo Fernandes, Michelle Monje, Jennifer R. Cochran, Poul H. Sorensen, Heike E. Daldrup-Link, Irving L. Weissman, Julien Sage, Ravindra Majeti, Carolyn R. Bertozzi, William A. Weiss, Crystal L. Mackall, Robbie G. Majzner
Journal: Nature Medicine (2022)
The BETTER trial: 6 Months restenosis after brachytherapy with a P32 balloon source Carlo Di Mario, Stefan Verheye, William Wijns, Alexandra Lansky, Remo Albiero, Giorgio Gimelli, Eric Eeckhout, Bernard de Bruyne, Guy Heydrickx, Maurice Buchbinder, Antonio Colombo. San Raffaele Hospital, Milan, Italy
Journal: Journal of the American College of Cardiology (2001)
The Patient
Authors: David W. Mathias
Journal: Annals of Internal Medicine (1986)

Ad Libitum1 January 1986The PatientDavid W. Mathias, M.D.David W. Mathias, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-1-138_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDoctor look beyond this frail body,This frozen smile.Why do you hide your fear,Fear troubles me.You shall one day be what I amAnd face what I faceWhy then can't you sit with me?Are you not concerned with my thoughts?Death is on the way—I know that.My family's smiles can't conceal the truth;They need their hope to go on,But you and I know what lies ahead.Sit and I will tell you,The wonders I have found.For I was full of hate and fear,Yet now I have found the peace... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Milwaukee, Wisconsin PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1986Volume 104, Issue 1Page: 138-138KeywordsFear ePublished: 1 December 2008 Issue Published: 1 January 1986 PDF downloadLoading ...