tbuckley/cabot-search huggingface dataset:
Synapsin III gene silencing redeems alpha-synuclein transgenic mice from Parkinson's disease-like phenotype
Authors: Gaia Faustini, Francesca Longhena, Anna Masato, Valentina Bassareo, Roberto Frau, Therése Klingstedt, Hamid Shirani, Viviana Brembati, Edoardo Parrella, Marika Vezzoli, K. Peter R. Nilsson, Marina Pizzi, Maria Grazia Spillantini, Luigi Bubacco, Arianna Bellucci
Journal: Molecular Therapy (2022)

Fibrillary aggregated α-synuclein (α-syn) deposition in Lewy bodies (LB) characterizes Parkinson's disease (PD) and is believed to trigger dopaminergic synaptic failure and a retrograde terminal-to-cell body neuronal degeneration. We described that the neuronal phosphoprotein synapsin III (Syn III) cooperates with α-syn to regulate dopamine (DA) release and can be found in the insoluble α-syn fibrils composing LB. Moreover, we showed that α-syn aggregates deposition, and the associated onset of synaptic deficits and neuronal degeneration occurring following adeno-associated viral vectors-mediated overexpression of human α-syn in the nigrostriatal system are hindered in Syn III knock out mice. This supports that Syn III facilitates α-syn aggregation. Here, in an interventional experimental design, we found that by inducing the gene silencing of Syn III in human α-syn transgenic mice at PD-like stage with advanced α-syn aggregation and overt striatal synaptic failure, we could lower α-syn aggregates and striatal fibers loss. In parallel, we observed recovery from synaptic vesicles clumping, DA release failure, and motor functions impairment. This supports that Syn III consolidates α-syn aggregates, while its downregulation enables their reduction and redeems the PD-like phenotype. Strategies targeting Syn III could thus constitute a therapeutic option for PD.
Acute Renal Failure
Authors: Frank A. Krumlovsky
Journal: JAMA (1978)

Fourteen cases of acute renal failure secondary to administration of radiographic contrast media were observed, eight within a 15-month period. No patient had multiple myeloma, and only three were diabetic. Predisposing factors included renal hypoperfusion, preexisting renal insufficiency, hyperuricemia, age of more than 60 years, solitary functioning kidney, and exposure to several contrast studies at closely spaced intervals. Control of blood volume and serum uric acid, appropriate spacing of radiographic studies, and possibly urinary alkalinization and hypouricosuric drugs in high-risk patients are recommended to decrease the incidence and morbidity of contrast-mediated nephropathy. (<i>JAMA</i>239:125-127, 1978)
Construction of Roman roads toward neuroeconomics
Authors: Toshiya Matsushima, Ai Kawamori, Yukiko Ogura
Journal: Behavioral and Brain Sciences (2021)

Abstract Neuroeconomics is still “under construction.” To be a leading discipline, it needs firm ecological rationale and neurobiological bases. “ Vigor ” supplies this infrastructure through the mathematics of the foraging theory and system-neuroscience evidence on utility and motor control. It will prepare us for the future neuroeconomics, if studied appropriately in the light of evolution.
PIEZO1 mediates a mechanothrombotic pathway in diabetes
Authors: Wandi Zhu, Shihui Guo, Max Homilius, Cissy Nsubuga, Shane H. Wright, Dajun Quan, Ashmita KC, Samuel S. Eddy, Rachelle A. Victorio, Manu Beerens, Robert Flaumenhaft, Rahul C. Deo, Calum A. MacRae
Journal: Science Translational Medicine (2022)

Hematopoietic cell selection based on PIEZO1 expression drives thrombosis risk in type 2 diabetes.
Current Therapeutic Options in Aortic Stenosis
Authors: Marko T. Boskovski, Thomas G. Gleason
Journal: Circulation Research (2021)

Aortic stenosis is the most common valvular disease requiring valve replacement. Valve replacement therapies have undergone progressive evolution since the 1960s. Over the last 20 years, transcatheter aortic valve replacement has radically transformed the care of aortic stenosis, such that it is now the treatment of choice for many, particularly elderly, patients. This review provides an overview of the pathophysiology, presentation, diagnosis, indications for intervention, and current therapeutic options for aortic stenosis.
AdvanTIG-206: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (BGB-A1217; OCI) plus anti-programmed cell death protein 1 (PD-1) mAb tislelizumab (TIS) plus BAT1706 versus (vs) TIS plus BAT1706 as first-line treatment for advanced hepatocellular carcinoma (HCC).
Authors: Jia Fan, Zhenggang Ren, Chiun Hsu, Yabing Guo, Tianqiang Song, Wentao Wang, Yee Chao, Yujuan Gao, Bai Li, Salvatore Ferro, Chia-Jui Yen
Journal: Journal of Clinical Oncology (2022)

TPS488 Background: Treatment with PD-1/programmed death-ligand 1 (PD-L1) inhibitors and anti-angiogenic agents has demonstrated significant survival improvements in patients with untreated HCC. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory immune checkpoint receptor upregulated on T cells and natural killer cells in multiple solid tumors. OCI is a novel, humanized mAb that binds TIGIT with high specificity and affinity, blocking interaction with its ligands on tumor cells. TIS is an anti-PD-1 mAb that has demonstrated clinical activity in patients with previously treated, unresectable HCC (NCT03419897). BAT1706 is a similar biological product to the anti-angiogenic agent bevacizumab. OCI combined with TIS and BAT1706 could further enhance both anti-angiogenic and anti-PD-1 therapies for patients with HCC. Methods: AdvanTIG-206 is a phase 2, randomized, open-label clinical study (NCT04948697). Patients aged ≥ 18 years with histologically confirmed advanced HCC that is not amenable to a curative treatment approach are eligible. Patients must have a Child-Pugh A score, ECOG PS ≤ 1, and have received no prior systemic therapy for HCC. Approximately 90 patients will be randomized 2:1 to OCI 900 mg combined with TIS 200 mg plus BAT1706 15 mg/kg (Arm A) or TIS 200 mg plus BAT1706 15 mg/kg (Arm B), all administered intravenously (once every 3 weeks [Q3W]). The primary endpoint is investigator-assessed objective response rate per RECIST v1.1. Radiological assessment of tumor response status will be performed Q6W for the first 48 weeks and Q12W thereafter. Secondary endpoints include duration of response, time to response, disease control rate, clinical benefit rate, and progression-free survival (all investigator-assessed overall survival), safety, pharmacokinetics, and immunogenicity. Study enrollment is ongoing. Clinical trial information: NCT04948697.
College Appointments.
Journal: JAMA (1883)

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
Response to: ‘Correspondence on ‘Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19- associated cytokine storm syndrome: results of the CHIC study’’ by Calvo-Aranda<i>et al</i>
Authors: Sofia Ramiro, Rémy Mostard, Robert BM Landewé
Journal: Annals of the Rheumatic Diseases (2020)
Errors in Figure
Authors: Ashley Choi, Hui-Jie Lee, Matthew Hartwig
Journal: JAMA Cardiology (2020)

Immortal time bias refers to a period of time during follow-up when the outcome (in our case, waitlist mortality) cannot occur.It is true that a candidate has to remain alive or eligible for transplant to receive an initial first-rank offer.However, we assessed risk of waitlist mortality after candidates received their initial first-rank offers, not at the time of listing, and thus immortal time bias does not apply. 3 This was done to assess center-level behavior toward offers that are intended for the sickest patients on the waitlist.Finally, as conveyed by earlier studies showing conflicting outcomes after the new allocation system began in October 2018, 4,5 we believe it would be premature to determine if the new system had a measurable impact on centers' organ acceptance behavior and waitlist mortality.The evolving clinical profiles of recipients and use of mechanical circulatory support devices along with an increasing use of hearts donated after circulatory death call for continuous reassessment of the new system.Our imminent goal is to start the conversation around what necessitates public reporting to help standardize organ allocation practices in the US.Acceptance rates may be a starting point as this can provide another objective measure to aid clinicians, patients, and their families who are choosing transplant programs.
Histologic and proteomic remodeling of the pulmonary veins and arteries in a porcine model of chronic pulmonary venous hypertension
Authors: Ahmed U Fayyaz, Michael S Sabbah, Surendra Dasari, Leigh G Griffiths, Hilary M DuBrock, Ying Wang, M Cristine Charlesworth, Barry A Borlaug, Sarah M Jenkins, William D Edwards, Margaret M Redfield
Journal: Cardiovascular Research (2022)

In heart failure (HF), pulmonary venous hypertension (PVH) produces pulmonary hypertension (PH) with remodeling of pulmonary veins (PV) and arteries (PA). In a porcine PVH model, we performed proteomic-based bioinformatics to investigate unique pathophysiologic mechanisms mediating PA and PV remodeling.
Clinical Trials of Different Concentrations of Oxygen and Nitrous Oxide for Obstetric Analgesia: Report to the Medical Research Council of the Committee on Nitrous Oxide and Oxygen Analgesia in Midwifery
Journal: BMJ (1970)

Trials have been organized by a Medical Research Council committee to assess the effectiveness and safety for analgesia in labour of oxygen and nitrous oxide mixtures in different proportions. In a preliminary trial concentrations of 50% and 60% v/v nitrous oxide were compared, but, as the replies of 409 mothers revealed little difference between the two, the results of administering either 50% or 70% nitrous oxide to 778 mothers were then compared. The data relating to normal labour, obtained on 501 of the mothers in this main trial, showed that the relief of pain given was much the same. There was a suggestion, however, that the higher concentration of nitrous oxide might be useful in abnormal labour. The proportion of mothers with normal deliveries who lost consciousness, though very small, was significantly higher with 70% nitrous oxide than with the lower concentration. Ninety-two per cent. of mothers found the gas and oxygen machine helpful, and midwives reported complete or good co-operation by 77% of those using it. It is concluded that the 50% oxygen and 50% nitrous oxide mixture can safely be used by unsupervised midwives.
Abstract P372: Trajectories in Fasting Glucose and Insulin Resistance During Young Adulthood and Measures of Cardiac Function and Structure in Middle Adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Michael P Bancks, Mercedes Carnethon, Lisa S Chow, David R Jacobs, Satoru Kishi, Joao Lima, Donald Lloyd-Jones, Jared Reis, Pam Schreiner, Rachel Zmora, Norrina B Allen
Journal: Circulation (2017)

Introduction: Whether trajectories in fasting glucose (FG) and insulin resistance (HOMA-IR) during young adulthood, before the onset of diabetes, are associated with cardiac function and structure in middle adulthood is unclear. Hypothesis: We tested the hypothesis that as compared to low-stable trajectory of FG and HOMA-IR, an increasing trajectory for each would be associated with worse cardiac structure and function in middle adulthood. Methods: We determined FG and HOMA-IR for 2,198 CARDIA participants, age 18-30 years, at baseline (1985-1986) and 7, 10, 15, 20, and 25 year follow-up exams who fasted for &gt;8 hours and were not pregnant and were free from diabetes at all exams. At year 30 (2016), Doppler echocardiography and 2D-guided M-mode echocardiography was performed, measuring left atrial dimension, relative wall thickness, left ventricular (LV) mass, LV mass indexed to height, LV ejection fraction percentage, LV end-diastolic and systolic volume, and LV mass to volume ratio. Trajectories were determined using latent class analysis (SAS Proc Traj). We used multivariable linear regression to estimate adjusted means for echo measures according to FG and HOMA-IR trajectory group after adjustment for potential confounding factors. Results: For individuals free from diabetes in midlife, we identified three trajectory groups for both FG and HOMA-IR, low-stable to increasing, moderate-increasing, and high-increasing. Compared to low-stable trajectory for FG, increasing trajectory was associated with greater LV end-diastolic volume, whereas for HOMA-IR increasing trajectory was associated with lower LV end-diastolic volume ( Table ). Increasing FG trajectory was also associated with greater left atrial dimension, while HOMA-IR was not. Conclusion: Trajectory of both FG and HOMA-IR during young adulthood, in the absence of diabetes, was most prominently and differentially associated with LV end-diastolic volume. Future research should elaborate on differential associations of FG and HOMA-IR trajectory.
Occurrence of implantable cardioverter defibrillator events in patients with syncope and a nonischemic dilated cardiomyopathy Andrea M. Russo, Ralph Verdino, Christa Schorr, Maureen Nicholas, Sanjay Dixit, Vickas Patel, Francis Marchlinski. University of Pennsylvania Health System, Philadelphia, PA
Journal: Journal of the American College of Cardiology (2001)
Abstract P019: Family History of Cardiovascular Disease is Associated With Cognitive Function: The Emory Healthy Aging Study
Authors: Margarethe E Goetz, Michele Marcus, Viola Vaccarino, Felicia Goldstein, Allan Levey, James Lah
Journal: Circulation (2017)

Background: Family history of cardiovascular disease (CVD) is a readily available risk indicator of future CVD, combining the influence of shared genetic, environmental and behavioral risk factors. Though CVD risk factors have been associated with an increased risk of cognitive impairment and decline, less is known about the association between family history of CVD and cognitive function. Evaluating this association may further elucidate the role of cardiovascular health in cognitive health. Methods: The Emory Healthy Aging Study isan ongoing prospective cohort study aimed at identifying predictors of healthy aging and age-related diseases. Participants are primarily residents of the Atlanta area, at least 18 years old, who completed an online baseline health survey. Multiple recruitment forums were used, including clinic waiting rooms, informational letters and emails, community events and online recruitment. Baseline information about demographic (age, race, gender), socioeconomic (education, household income), and health behavior factors (physical activity, smoking) as well as personal health (diabetes, hyperlipidemia, and hypertension) and family health history were collected by online survey. Family history of CVD was defined as self-reported history for any parent or sibling of coronary artery disease, myocardial infarction, or stroke. Cognitive function was measured using the validated Cognitive Function Instrument (CFI) with scores ranging between 0-14 (lower is better). The association between family history of CVD and CFI score was assessed using multivariable linear regression, adjusting for demographic, socioeconomic, lifestyle and CVD risk factors, as well as family history of mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Results: We studied 3801 participants (75% female, 85% white, 10% black, and 5% other), recruited between October 2015 and October 2016. Mean age was 59±13 years and 61% reported a family history of CVD. Adjusting for age, gender, race, education, household income, exercise habits, smoking status and family history of MCI or AD, family history of CVD was associated with poorer cognitive performance (β=0.26; 95% CI (0.12, 0.41)). Additional adjustment for hypertension, hyperlipidemia, diabetes and BMI only slightly attenuated estimates (β=0.22; 95% CI (0.08, 0.41)). In the same model, the estimated β for family history of cognitive impairment was similar: 0.22 (0.07, 0.37). Conclusion: In this cross-sectional study of people from the community, family history of CVD was associated with poorer cognitive function, and this association was of the same magnitude as having a first-degree family member with a history of cognitive impairment. Although longitudinal data are needed, these results underscore the link between cardiovascular and neurocognitive health and potential role of shared genetic and behavioral factors.
Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies
Authors: Katia de Paiva Lopes, Gijsje J. L. Snijders, Jack Humphrey, Amanda Allan, Marjolein A. M. Sneeboer, Elisa Navarro, Brian M. Schilder, Ricardo A. Vialle, Madison Parks, Roy Missall, Welmoed van Zuiden, Frederieke A. J. Gigase, Raphael Kübler, Amber Berdenis van Berlekom, Emily M. Hicks, Chotima Bӧttcher, Josef Priller, René S. Kahn, Lot D. de Witte, Towfique Raj
Journal: Nature Genetics (2022)
Access to health care and preventable hospitalizations
Authors: J. J. Frey
Journal: JAMA (1995)

<h3>To the Editor.</h3> —In the article by Dr Bindman and colleagues<sup>1</sup>it was unsettling to see the authors state that "[a]ccess to care was inversely associated with the hospitalization rates for the five chronic conditions." This is not because their data are incompatible with many of our experiences, but because they echo the landmark article by Hart<sup>2</sup>published 24 years ago in which he first used the term "inverse care law." Hart showed, via analyses of the burdens of illness in regions of Great Britain with variations of social class and variations of physician quality, that "the availability of good medical care tends to vary inversely with the need for it in the population served." At the time, Hart's "law" stirred many in the National Health Service to address inequities in quality and access for the working class and the poor in both urban and rural areas of
EXPERIENCE OF AN AMERICAN PHYSICIAN IN MEXICO.
Authors: D. H. GALLOWAY
Journal: JAMA (1895)

<h3>A Case of Cancrum Oris.</h3> —One day happening to be in the dispensary conducted by Dr. Salmans, in Silao, I saw a child brought in which the Doctor had no sooner seen than he exclaimed: "Take it away! It will die! " Although I had never seen a case of cancrum oris, it was scarcely necessary for him to name the disease. The appearance and odor were something frightful, and death was then but a question of a few hours. When the Doctor had finished prescribing for the thirty or forty patients waiting, I asked him about the disease. He told me that in some two years' practice in that state, he had seen eight or ten cases of this dreadful malady; that he did nothing more than tell the people that the disease would be fatal, and dismissed them. He also informed me that the Mexican doctors pursued the same
Abstract 38: Bioreactor Based Approach for Valve Tissue Engineering: Novel Application of Decellularized Porcine Pericardium
Authors: Francesco Amadeo, Gianluca Polvani, Marco Agrifoglio, Federica Boschetti, Maurizio Pesce, Rosaria Santoro
Journal: Circulation Research (2017)

Background: Aldehyde-fixed pericardium is commonly used in valve implant manufacturing. Despite its wide employment, this tissue undergoes chronic rejection that limits implant performance and durability. In this work, we employed a method to engineer a leaflet-like tissue by seeding aortic valve interstitial cells (VIC) into fixative-free decellularized pericardium using a bioreactor based approach. Methods: Following treatment with hypotonic buffer (Tris-HCl) to induce cell lysis, porcine pericardium was incubated with TritonX-100, to remove adipose tissue and then treated with sodium dodecylsulfate to wash cellular debris. DNA was removed by incubation into a DNAse I solution. Pericardium permeability was measured on samples before and after decellularization (pressure from 735 Pa to 2200 Pa). A direct perfusion bioreactor was employed to seed (3days, 3ml/min) porcine VICs (6.5E+5 cell/scaffold) into decellularized pericardium patches (6mm diameters) and perform long-term culture (up to 14 days, 0.03ml/min). Cell seeding efficiency (Day 3) and cell proliferation (Day 7-14) were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) staining, histological analyses and fluorescence staining for quiescent/activated VIC markers (DAPI, vimentin, α-smooth muscle actin). Results: Permeability tests revealed a significant increase in decellularized samples (1-way ANOVA p &lt; 0.05), thus supporting its use in a direct perfusion bioreactor system. MTT staining revealed homogeneous cell seeding distribution, supported by DAPI staining, showing efficient cellularization through the whole patch volume. Computer-based cell nuclei counting revealed a significant cell increase from day 3 to 7 and 14 ( p &lt;0.05 1-way ANOVA). Immunofluorescence showed a marked reduction of αSMA in cells populating the inner layers. Conclusions: Our data show, for the first time, the capability to seed and culture VICs into a cell/fixative free pericardium with a direct perfusion system. Moreover, the use of pericardium treated with our decellularization procedure and recellularized under dynamic conditions supports a more physiological growth of VIC, as suggested by downregulation of αSMA in the inner pericardium layer.