tbuckley/cabot-search huggingface dataset:
AXL and MET in Hepatocellular Carcinoma: A Systematic Literature Review
Authors: Chih-Hung Hsu, Yi-Hsiang Huang, Shi-Ming Lin, Chiun Hsu
Journal: Liver Cancer (2022)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Multikinase inhibitors (MKIs) have been shown to improve survival in patients with hepatocellular carcinoma (HCC) compared with placebo. Distinct from other MKIs, cabozantinib has inhibitory activity for both AXL and MET. This review considers the literature elucidating the role of AXL and MET in HCC progression, treatment resistance, and immunomodulation. A systematic search of the PubMed database was conducted on November 16, 2020, and identified a total of 174 search results. A further 36 potentially relevant articles were identified based on the authors’ knowledge. After initial screening by title/abstract, 159 underwent full-text screening and we identified 69 original research articles reporting empirical data from in vitro or in vivo models of HCC evaluating the effects of manipulating AXL or MET signaling on tumorigenic behavior. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; AXL expression is highly correlated with HCC progression and outcomes and has been reported to be involved in transforming growth factor-β and the regulation of PI3K/AKT, ERK/MAPK, and CCN proteins. MET protein expression is increased in HCC with the highest histological grade and has been reported to be involved in the regulation of PI3K/AKT, PLCγ/DAG/PKC, and MAPK/ERK signaling. Both AXL and MET are key regulators of sorafenib resistance in HCC. In terms of immunomodulation, there are data to indicate that AXL and MET interact with the immune components of the tumor microenvironment and promote tumorigenesis and treatment resistance. In addition, AXL was found to play a potential role in the development of a protumorigenic neutrophil phenotype in HCC. Combined inhibition of MET and programmed cell death protein resulted in additive reduction of HCC cell growth. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; AXL and MET play key roles in HCC progression, treatment resistance, and immunomodulation. Continued development of drugs that target these receptor tyrosine kinases appears likely to represent a useful strategy to improve outcomes for patients with HCC.
Bioassaying for Ozone with Pollen Systems
Authors: William A. Feder
Journal: Environmental Health Perspectives (1981)

Sensitivity to ozone of pollen germinating in vitro is closely correlated with ozone sensitivity of the pollen parent. Ozone-sensitive and tolerant pollen populations have been identified in tobacco, petunia, and tomato cultivars. The rate of tube elongation can be reversibly slowed or stopped by exposure to low concentrations of ozone. Tube growth rates in the presence of a range of ozone dosages, of pollen populations exhibiting differing ozone sensitivity can be measured and different growth rates can be correlated with ozone dosages. The performance of selected pollen populations can then be used to bioassay ozone in ambient air by introducing the air sample into a growth chamber where ozone-sensitive pollen in growing. Petunia and tobacco pollen are especially useful because they store well at ordinary freezer temperatures and do not require special preparation prior to storage. Modified Brewbacker's growth medium is suitable for growth of both these pollen types. Four useful cultivars are Bel W-3, ozone-sensitive and Bel B, ozone-tolerant tobacco, and White Bountiful, ozone-sensitive and Blue Lagoon, ozone-tolerant petunia. Observations can be made directly by using a TV scanner, or by time lapse or interval photography. Year-round pollen production can be achieved in the greenhouse. Harvested pollen can be tested, packaged, and transported to user facilities without loss of vigor. Pollen populations are inexpensive to produce, respond reliably, and are simple to use as a bioassay for air quality.
Fungal Arthritis
Authors: George E. Ehrlich
Journal: JAMA (1978)

It has been claimed that each generation needs its own biographies of historical personages retold in its own terms. The dictum may hold true for medical problems as well. As we make inroads into an understanding of various idiopathic diseases, we may lose sight of the real continuation of infectious diseases, especially those that are not too common, too acute, or too easily thought of. Fungal infections are among those not usually recognized. Some, like mycetoma, tend to be monoarticular, producing grotesque disfiguring swelling through which sinus tracts burrow. Actinomycetes are chiefly responsible, including<i>Madurella, Phialophora verrucosa</i>, and<i>Allescheria</i>, the last-named most often guilty of producing this disorder in the United States.<sup>1</sup>The local introduction into the skin, chiefly in people working outside in hot areas, is probably responsible. Those who see many cases in tropical countries think of the diagnosis. The occasional occurrence in the temperate climates makes
Part 11: Neonatal Resuscitation
Authors: Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Dianne L. Atkins, Leon Chameides, Jay P. Goldsmith, Ruth Guinsburg, Mary Fran Hazinski, Colin Morley, Sam Richmond, Wendy M. Simon, Nalini Singhal, Edgardo Szyld, Masanori Tamura, Sithembiso Velaphi, Khalid Aziz, David Boyle, Steven Byrne, Peter Davis, William A. Engle, Marilyn B. Escobedo, Maria Fernanda de Almeida, David Field, Judith Finn, Louis P. Halamek, Jane E. McGowan, Douglas D. McMillan, Lindsay Mildenhall, Rintaro Mori, Susan Niermeyer, Colm O'Donnell, Yacov Rabi, Steven A. Ringer, Jasmeet Soar, Benjamin J. Stenson, Enrique Udaeta, Dharmapuri Vidyasagar, Michael Watkinson, Gary M. Weiner, Myra H. Wyckoff
Journal: Circulation (2010)
An Appeal.
Authors: Howard A. Kelly
Journal: JAMA (1905)

Baltimore, April 6, 1905. <h3>To the Editor:</h3> —Would it in any way be contrary to the policy ofThe Journalto insert the following statement? One of the best known physicians of this country, a woman who has given her life to the arduous duties of the profession, as well as to work in numerous charitable associations, especially in those which are helpful to women, has suddenly been thrown out of a life of great activity and usefulness into one of absolute inactivity and dependence. The medical profession of Chicago, and I think of the country at large, will
Alzheimer's Disease
Authors: B. H. Glover
Journal: JAMA (1985)

The preliminary chapter on contributors lists 74 major scientists of national and international origin and stature in geriatrics, gerontology, behavioral sciences, psychiatry, neurology, pharmacology, communicative disorders, neuropathology, genetics, neurochemistry, anatomy, experimental therapeutics, endocrinology, and many other specialty fields all related to the subject of Alzheimer's disease investigation and research. Many of the references cited refer to the works of these contributors. The two-page preface by the editor is a smooth, crisp introduction to the scholarly and well-referenced chapters that follow, covering the most substantive material on the subject written in the last 20 years. The rationale for a formal standard of reference is well explained in the discussion on the authenticated pattern of neglect of this historic illness, now termed "the disease of the century" and "the fourth greatest cause of mortality in developed nations." In chapter 1 entitled "Overview of Current Concepts of Alzheimer's Disease," senile dementia and age-associated
Issue 1 - “Update on adverse respiratory effects of outdoor air pollution”. Part 1): Outdoor air pollution and respiratory diseases: A general update and an Italian perspective
Authors: S. De Matteis, F. Forastiere, S. Baldacci, S. Maio, S. Tagliaferro, S. Fasola, G. Cilluffo, S. La Grutta, G. Viegi
Journal: Pulmonology (2022)

to summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects.the recent literature indicates that there is strong evidence for causal relationships between PM2.5 air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults. Italy, a Southern European country, faces a more threatening air pollution challenge because of the effects of both anthropogenic pollutants and natural dust (particulate matter, PM). The 2020 Report of the European Environment Agency highlighted the number of premature deaths in Italy attributable to main pollutants: 52,300 for PM2.5, 10,400 for NO2 and 3,000 for O3 in 2018. In Italy, original time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality and increased risk of respiratory diseases in people living in urban areas.adverse health effects of air pollutants, even at low levels, have been confirmed by recent epidemiological studies. Further studies should focus on the potential link between air pollution exposure and respiratory infections. This topic has become particularly important in the current SARS-COV-2 pandemic. Based on strong scientific evidence, the Italian government, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD)-Italy at the Ministry of Health, the scientific respiratory societies and the patients' associations, as well as others in the health sector and civil society, must increase their engagement in advocacy for clean air policies, especially in light of the new Air Quality Guidelines of the World Health Organization.
Causal complexity demands community coordination
Authors: Beau Sievers, Evan DeFilippis
Journal: Behavioral and Brain Sciences (2022)

Abstract Yarkoni's argument risks skepticism about the very possibility of social science: If social phenomena are too causally complex, normal scientific methods could not possibly untangle them. We argue that the problem of causal complexity is best approached at the level of scientific communities and institutions, not the modeling practices of individual scientists.
Elemental diets.
Authors: R I Russel
Journal: Gut (1975)

Progress report Elemental dietsThe term 'elemental diet' is applied to a food which contains an elemental protein source, in the form of amino acids, with other easily digestible nutrients, minerals, and vitamins added; fat is present in very small quan- tities.Such a diet may also be described as 'chemically defined', the elemental components being pure chemical entities.
Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas
Authors: Justyna M Przystal, Chiara Cianciolo Cosentino, Sridevi Yadavilli, Jie Zhang, Sandra Laternser, Erin R Bonner, Rachna Prasad, Adam A Dawood, Nina Lobeto, Wai Chin Chong, Matt C Biery, Carrie Myers, James M Olson, Eshini Panditharatna, Bettina Kritzer, Sulayman Mourabit, Nicholas A Vitanza, Mariella G Filbin, Geoffry N de Iuliis, Matthew D Dun, Carl Koschmann, Jason E Cain, Michael A Grotzer, Sebastian M Waszak, Sabine Mueller, Javad Nazarian
Journal: Neuro-Oncology (2022)

Abstract Background Pediatric diffuse midline gliomas (DMGs) are incurable childhood cancers. The imipridone ONC201 has shown early clinical efficacy in a subset of DMGs. However, the anticancer mechanisms of ONC201 and its derivative ONC206 have not been fully described in DMGs. Methods DMG models including primary human in vitro (n = 18) and in vivo (murine and zebrafish) models, and patient (n = 20) frozen and FFPE specimens were used. Drug-target engagement was evaluated using in silico ChemPLP and in vitro thermal shift assay. Drug toxicity and neurotoxicity were assessed in zebrafish models. Seahorse XF Cell Mito Stress Test, MitoSOX and TMRM assays, and electron microscopy imaging were used to assess metabolic signatures. Cell lineage differentiation and drug-altered pathways were defined using bulk and single-cell RNA-seq. Results ONC201 and ONC206 reduce viability of DMG cells in nM concentrations and extend survival of DMG PDX models (ONC201: 117 days, P = .01; ONC206: 113 days, P = .001). ONC206 is 10X more potent than ONC201 in vitro and combination treatment was the most efficacious at prolonging survival in vivo (125 days, P = .02). Thermal shift assay confirmed that both drugs bind to ClpP, with ONC206 exhibiting a higher binding affinity as assessed by in silico ChemPLP. ClpP activation by both drugs results in impaired tumor cell metabolism, mitochondrial damage, ROS production, activation of integrative stress response (ISR), and apoptosis in vitro and in vivo. Strikingly, imipridone treatment triggered a lineage shift from a proliferative, oligodendrocyte precursor-like state to a mature, astrocyte-like state. Conclusion Targeting mitochondrial metabolism and ISR activation effectively impairs DMG tumorigenicity. These results supported the initiation of two pediatric clinical trials (NCT05009992, NCT04732065).
Chronic circadian disruption on a high-fat diet impairs glucose tolerance
Authors: Kirsi-Marja Zitting, Ramalingam Vetrivelan, Robin K. Yuan, Nina Vujovic, Wei Wang, Sathyajit S. Bandaru, Stuart F. Quan, Elizabeth B. Klerman, Frank A.J.L. Scheer, Orfeu M. Buxton, Jonathan S. Williams, Jeanne F. Duffy, Clifford B. Saper, Charles A. Czeisler
Journal: Metabolism (2022)
COCAINE.
Authors: Sarah Hackett Stevenson
Journal: JAMA (1884)

Wiesbaden, Germany, Dec. 1, 1884. Mr. Editor: E. Merck, the celebrated pharmaceutist of Darmstadt, has kindly furnished me with the following items in regard to the now famous remedy—cocaine. The chemical formula according to Lossen is: C<sub>17</sub>H<sub>24</sub>NO<sub>4</sub>. Cocaine is the alkaloid contained in the coca leaves (Erythoxylon Coca Lam) which was first isolated by Niemann. In 1862, Lossen discovered a second principle contained in the same leaves, viz.: hygein, which is of a volatile nature, and has received but little investigation so far; it seems to have a weak and hardly characteristic action. The leaves further contain ecgonin, coca tannin and a peculiar wax. The coca crystals belong to the monocline system, melt at 98° C., easily soluble in alcohol, more easily in ether, but only dissolve in 704 parts water. The cocaine<i>salts</i>, however, are easily soluble in water. The first reports of the
Limited impact of <scp>COVID</scp> ‐19‐related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis
Authors: Tobias E. Sangers, Marlies Wakkee, Eline C. Kramer‐Noels, Tamar Nijsten, Marieke W.J. Louwman, Elisabeth H. Jaspars, Loes M. Hollestein
Journal: British Journal of Dermatology (2022)

Background The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages. Objectives To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods. Methods In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre-COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t-test. pT-stage groups were compared using a χ2-test. Outcomes were corrected for multiple testing using the false discovery rate. Results In total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii–v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre-COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre-COVID (i) and COVID-affected periods (ii–v) for cSCCs. Conclusions To date, the diagnostic delay caused by COVID-19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow-up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term.
Systems Chronotherapeutics
Authors: Annabelle Ballesta, Pasquale F. Innominato, Robert Dallmann, David A. Rand, Francis A. Lévi
Journal: Pharmacological Reviews (2017)

Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are controlled by the circadian timing system. Thus, the tolerability of nearly 500 medications varies by up to fivefold according to circadian scheduling, both in experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved the circadian timing system as a function of drug timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated in randomized clinical trials, especially for cancer and inflammatory diseases. However, recent technological advances have highlighted large interpatient differences in circadian functions resulting in significant variability in chronotherapy response. Such findings advocate for the advancement of personalized chronotherapeutics through interdisciplinary systems approaches. Thus, the combination of mathematical, statistical, technological, experimental, and clinical expertise is now shaping the development of dedicated devices and diagnostic and delivery algorithms enabling treatment individualization. In particular, multiscale systems chronopharmacology approaches currently combine mathematical modeling based on cellular and whole-body physiology to preclinical and clinical investigations toward the design of patient-tailored chronotherapies. We review recent systems research works aiming to the individualization of disease treatment, with emphasis on both cancer management and circadian timing system–resetting strategies for improving chronic disease control and patient outcomes.
J Laboratory &amp;amp; Clinical Medicine, St. Louis
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
Urban landscape and street-design factors associated with road-traffic mortality in Latin America between 2010 and 2016 (SALURBAL): an ecological study
Authors: D Alex Quistberg, Philipp Hessel, Daniel A Rodriguez, Olga L Sarmiento, Usama Bilal, Waleska Teixeira Caiaffa, J Jaime Miranda, Maria de Fatima de Pina, Akram Hernández-Vásquez, Ana V Diez Roux
Journal: The Lancet Planetary Health (2022)

BackgroundRoad-traffic injuries are a key cause of death and disability in low-income and middle-income countries, but the effect of city characteristics on road-traffic mortality is unknown in these countries. The aim of this study was to determine associations between city-level built environment factors and road-traffic mortality in large Latin American cities.MethodsWe selected cities from Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Panama, and Peru; cities included in the analysis had a population of at least 100 000 people. We extracted data for road-traffic deaths that occurred between 2010 and 2016 from country vital registries. Deaths were grouped by 5-year age groups and sex. Road-traffic deaths were identified using ICD-10 codes, with adjustments for ill-defined codes and incomplete registration. City-level measures included population, urban development, street design, public transportation, and social environment. Associations were estimated using multilevel negative binomial models with robust variances.Findings366 cities were included in the analysis. There were 328 408 road-traffic deaths in nearly 3·5 billion person-years across all countries, with an average crude rate of 17·1 deaths per 100 000 person-years. Nearly half of the people who died were younger than 35 years. In multivariable models, road-traffic mortality was higher in cities where urban development was more isolated (rate ratio [RR] 1·05 per 1 SD increase, 95% CI 1·02–1·09), but lower in cities with higher population density (0·94, 0·90–0·98), higher gross domestic product per capita (0·96, 0·94–0·98), and higher intersection density (0·92, 0·89–0·95). Cities with mass transit had lower road mortality rates than did those without (0·92, 0·86–0·99).InterpretationUrban development policies that reduce isolated and disconnected urban development and that promote walkable street networks and public transport could be important strategies to reduce road-traffic deaths in Latin America and elsewhere.FundingWellcome Trust.