tbuckley/cabot-search huggingface dataset:
Intergenerational Echoes of Climate Change
Authors: Dolores Malaspina, Elizabeth A. Howell, Julie Spicer
Journal: JAMA Psychiatry (2020)

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 Psychiatry 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 Psychiatry journal
PLAGL2‐EGFR‐HIF‐1/2α Signaling Loop Promotes HCC Progression and Erlotinib Insensitivity
Authors: Weiwei Hu, Shufang Zheng, Haixin Guo, Beiying Dai, Jiaping Ni, Yaohong Shi, Hanrui Bian, Lanxin Li, Yumeng Shen, Mo Wu, Zhoutong Tian, Guilai Liu, Md Amir Hossain, Hongbao Yang, Duowei Wang, Qin Zhang, Jun Yu, Lutz Birnbaumer, Jifeng Feng, Decai Yu, Yong Yang
Journal: Hepatology (2020)

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, hence a major public health threat. Pleomorphic adenoma gene like-2 (PLAGL2) has been reported to play a role in tumorigenesis. However, its precise function in HCC remains poorly understood.In this study, we demonstrated that PLAGL2 was up-regulated in HCC compared with that of adjacent nontumorous tissues and also correlated with overall survival times. We further showed that PLAGL2 promoted HCC cell proliferation, migration, and invasion both in vitro and in vivo. PLAGL2 expression was positively correlated with epidermal growth factor receptor (EGFR) expression. Mechanistically, this study demonstrated that PLAGL2 functions as a transcriptional regulator of EGFR and promotes HCC cell proliferation, migration, and invasion through the EGFR-AKT pathway. Moreover, hypoxia was found to significantly induce high expression of PLAGL2, which promoted hypoxia inducible factor 1/2 alpha subunit (HIF1/2A) expression through EGFR. Therefore, this study demonstrated that a PLAGL2-EGFR-HIF1/2A signaling loop promotes HCC progression. More importantly, PLAGL2 expression reduced hepatoma cells' response to the anti-EGFR drug erlotinib. PLAGL2 knockdown enhanced the response to erlotinib.This study reveals the pivotal role of PLAGL2 in HCC cell proliferation, metastasis, and erlotinib insensitivity. This suggests that PLAGL2 can be a potential therapeutic target of HCC.
Covid-19: protecting patients in hospital for neurorehabilitation and their therapists
Authors: Jonathan Mamo, Beenish Feroz, Sazan Mahmood
Journal: BMJ (2020)

One of the unforeseen challenges for NHS hospitals during the covid-19 epidemic1 is ensuring the safety of patients who would normally be residing in the hospital at this time of year, such as those undergoing neurorehabilitation. A large proportion of …
Severe liver failure during SARS-CoV-2 infection
Authors: Sabine Weber, Julia Mayerle, Michael Irlbeck, Alexander L Gerbes
Journal: Gut (2020)

We read with interest the recently described affections of the GI system in coronavirus disease (COVID-19).1 2 In addition to the effects on the gut, mild abnormalities in liver aminotransferase levels have been observed.3 4 We here report a previously non-described severe liver failure in a patient with COVID-19.

A 65-year-old man was admitted to our emergency department with fever up to 40°C, dry cough and dyspnoea. The chest CT scan showed typical features of COVID-19, such as ground-glass opacities and peripheral consolidations. A throat swab confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aminotransferase concentrations were slightly increased (alanine aminotransferase (ALT) 69 U/L and aspartate aminotransferase (AST) 92 U/L; upper limit of normal (ULN) ≤49 U/L). He had been receiving long-term treatment with hydrochlorothiazide and ramipril for arterial hypertension as sole medications and had no history of liver disease.

The patient was admitted to the isolation ward and was given supplementary oxygen. He received piperacillin/tazobactam and azithromycin according to hospital standards, as well as paracetamol (1 g, up to two times per day). …
Affective Disorders: Drug Actions in Animals and Man. Handbook of Psychopharmacology, Vol. 14, <i>edited by Leslie L. Iversen, Susan D. Iversen, and Solomon H. Snyder. New York, N. Y., Plenum Press, 1978, 369 pp., $29.50</i>
Authors: J. Mendlewicz
Journal: American Journal of Psychiatry (1979)
Epidemiological Assessment of Imported Coronavirus Disease 2019 (COVID-19) Cases in the Most Affected City Outside of Hubei Province, Wenzhou, China
Authors: Yi Han, Yi Liu, Liyuan Zhou, Enguo Chen, Pengyuan Liu, Xiaoqing Pan, Yan Lu
Journal: JAMA Network Open (2020)

Wuhan to Wenzhou from January 10 to 23
Pulmonary arterial hypertension with below threshold pulmonary vascular resistance
Authors: Seshika Ratwatte, James Anderson, Geoffrey Strange, Carolyn Corrigan, Nicholas Collins, David S. Celermajer, Nathan Dwyer, John Feenstra, Dominic Keating, Eugene Kotlyar, Melanie Lavender, Helen Whitford, Ken Whyte, Trevor Williams, Jeremy P. Wrobel, Anne Keogh, Edmund M. Lau
Journal: European Respiratory Journal (2020)

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25-30 mmHg), PAWP 13 mmHg (IQR 11-14 mmHg) and PVR 2.2 Wood units (IQR 1.9-2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280-416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7-96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32-101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and "borderline" PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.
NeuroSAFE PROOF Randomised Controlled Feasibility Study: Brief Report of Perioperative Outcomes, Histological Concordance, and Feasibility
Authors: Eoin Dinneen, Aiman Haider, Alex Freeman, Jon Oxley, Tim Briggs, Senthil Nathan, John Kelly, Jack Grierson, Clare Allen, Raj Persad, Jonathan Aning, Neil Oakley, Imran Ahmad, Lorenzo Dutto, Greg Shaw
Journal: European Urology (2020)
The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study
Authors: Barbara A Conley, Lou Staudt, Naoko Takebe, David A Wheeler, Linghua Wang, Maria F Cardenas, Viktoriya Korchina, Jean Claude Zenklusen, Lisa M McShane, James V Tricoli, Paul M Williams, Irina Lubensky, Geraldine O’Sullivan-Coyne, Elise Kohn, Richard F Little, Jeffrey White, Shakun Malik, Lyndsay N Harris, Bhupinder Mann, Carol Weil, Roy Tarnuzzer, Chris Karlovich, Brian Rodgers, Lalitha Shankar, Paula M Jacobs, Tracy Nolan, Sean M Berryman, Julie Gastier-Foster, Jay Bowen, Kristen Leraas, Hui Shen, Peter W Laird, Manel Esteller, Vincent Miller, Adrienne Johnson, Elijah F Edmondson, Thomas J Giordano, Benjamin Kim, S Percy Ivy
Journal: JNCI Journal of the National Cancer Institute (2020)

Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses.
Lovastatin Enhances Ecto-5′-Nucleotidase Activity and Cell Surface Expression in Endothelial Cells
Authors: S. Ledoux, D. Laouari, M. Essig, I. Runembert, G. Trugnan, J.B. Michel, G. Friedlander
Journal: Circulation Research (2002)

Extracellular adenosine production by the GPI-anchored Ecto-5′-Nucleotidase (Ecto-5′-Nu) plays an important role in the cardiovascular system, notably in defense against hypoxia. It has been previously suggested that HMG-CoA reductase inhibitors (HRIs) could potentiate the hypoxic stimulation of Ecto-5′Nu in myocardial ischemia. In order to elucidate the mechanism of Ecto-5′-Nu stimulation by HRIs, Ecto-5′-Nu activity and expression were determined in an aortic endothelial cell line (SVAREC) incubated with lovastatin. Lovastatin enhanced Ecto-5′-Nu activity in a dose-dependent manner. This increase was not supported by de novo synthesis of the enzyme because neither the mRNA content nor the total amount of the protein were modified by lovastatin. By contrast, lovastatin enhanced cell surface expression of Ecto-5′-Nu and decreased endocytosis of Ecto-5′-Nu, as evidenced by immunostaining. This effect appeared unrelated to modifications of cholesterol content or Ecto-5′-Nu association with detergent-resistant membranes. The effect of lovastatin was reversed by mevalonate, the substrate of HMG-CoA reductase, by its isoprenoid derivative, geranyl-geranyl pyrophosphate, and by cytotoxic necrotizing factor, an activator of Rho-GTPases. Stimulation of Ecto-5′-Nu by lovastatin enhanced the inhibition of platelet aggregation induced by endothelial cells. In conclusion, lovastatin enhances Ecto-5′-Nu activity and membrane expression in endothelial cells. This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5′-Nu endocytosis through a decrease of Rho-GTPases isoprenylation.
Engineering Tough, Injectable, Naturally Derived, Bioadhesive Composite Hydrogels
Authors: Maryam Tavafoghi, Amir Sheikhi, Rumeysa Tutar, Jamileh Jahangiry, Avijit Baidya, Reihaneh Haghniaz, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2020)

Engineering mechanically robust bioadhesive hydrogels that can withstand large strains may open new opportunities for the sutureless sealing of highly stretchable tissues. While typical chemical modifications of hydrogels, such as increasing the functional group density of crosslinkable moieties and blending them with other polymers or nanomaterials have resulted in improved mechanical stiffness, the modified hydrogels have often exhibited increased brittleness resulting in deteriorated sealing capabilities under large strains. Furthermore, highly elastic hydrogels, such as tropoelastin derivatives are highly expensive. Here, gelatin methacryloyl (GelMA) is hybridized with methacrylate-modified alginate (AlgMA) to enable ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid hydrogels provide a photocrosslinkable, injectable, and bioadhesive platform with an excellent toughness that can be tailored using divalent cations, such as calcium. This class of hybrid biopolymers with more than 600% improved toughness compared to GelMA may set the stage for durable, mechanically resilient, and cost-effective tissue sealants. This strategy to increase the toughness of hydrogels may be extended to other crosslinkable polymers with similarly reactive moieties.
Proactive Integration of Geriatrics and Palliative Care Principles Into Practice for Chronic Obstructive Pulmonary Disease
Authors: Anand S. Iyer, J. Randall Curtis, Diane E. Meier
Journal: JAMA Internal Medicine (2020)

This Viewpoint proposes that clinicians who routinely care for older patients with chronic obstructive pulmonary disease should proactively integrate geriatrics and palliative care principles into their daily practice.
A Double‐Layered Microneedle Platform Fabricated through Frozen Spray‐Coating
Authors: Xiaoyu Ning, Christian Wiraja, Daniel Chin Shiuan Lio, Chenjie Xu
Journal: Advanced Healthcare Materials (2020)

This work reports a frozen spray-coating method for the fabrication of double-layered microneedles (MNs). Taking swellable methacrylated hyaluronic acid (MeHA)-derived MNs as the model, both hydrophobic molecules (Nile red, Cy5) and hydrophilic ones (FITC, FITC-Dextran, Insulin) can be homogeneously coated without impacting the mechanical properties of the original MeHA MNs. The prepared double-layered MNs can execute multiple roles. It is demonstrated that insulin-coated MeHA double-layered MNs allow the effective delivery of the insulin into circulation of mice for controlling the blood glucose level while they also permit the extraction of skin interstitial fluid for the timely analysis of the biomarker (glucose).
PD-1 blockade-unresponsive human tumor-infiltrating CD8+ T cells are marked by loss of CD28 expression and rescued by IL-15
Authors: Kyung Hwan Kim, Hong Kwan Kim, Hyung-Don Kim, Chang Gon Kim, Hoyoung Lee, Ji Won Han, Seong Jin Choi, Seongju Jeong, Minwoo Jeon, Hyunglae Kim, Jiae Koh, Bo Mi Ku, Su-Hyung Park, Myung-Ju Ahn, Eui-Cheol Shin
Journal: Cellular and Molecular Immunology (2020)
Abstract 302: Pediatric CPR Performance During One Year of RQI in a Pediatric Emergency Department
Authors: Aaron Donoghue, Mary Kate Abbadessa, Shannon Gaines, Ichiro Watanabe, Richard Hanna, Debra Heard, Sage Myers, Dana E Niles, Vinay M Nadkarni, Russell E Griffin
Journal: Circulation (2019)

The Resuscitation Quality Improvement Program is a low-dose high-frequency training method for CPR skills. Evidence linking high-frequency training to improved performance during actual CPR is lacking. We have previously reported on the simultaneous use of video review and chest compression (CC) monitoring devices to describe CC quality at the level of individual providers. We sought to evaluate CC quality in pediatric CPR over a one year period following RQI implementation. Methods: Observational study in a pediatric ED where codes are videorecorded and where all providers were enrolled in RQI in October 2017. Video review is used to identify CPR providers and measure the duration of CC segments they perform. A monitor device is used to record CC depth and rate, allowing summarization of CC parameters for those individual time segments (i.e. CC performance by individual providers). CCs were analyzed by ‘compressor segment’, defined as the period of time where a single provider performed chest compressions until replaced by another. Data was summarized by quarter; change over time was analyzed by mixed effect logistic regression modeling adjusting for quarter and segment duration as fixed effects. Results: 159 providers enrolled in RQI. Data for 18 events totaling 206 CC segments were analyzed. 52 providers performed CC at some point during the study period. CC segments are graphed per quarter in Figure 1. There were no significant differences in proportion of CC segments meeting guidelines during the study period. Conclusions: CPR events in our ED are infrequent and a minority of providers perform CPR in routine clinical practice. Over a 15 month period following the implementation of RQI in a pediatric ED, CC quality during CPR events in children did not improve with time, although our analysis was limited by sample size constraints. Future research should expand this method to examine the impact of varied retraining intervals and varied participant groups on CC quality.
Lung Recruitment and Pendelluft Resolution after Less Invasive Surfactant Administration in a Preterm Infant
Authors: Walusa Assad Gonçalves-Ferri, Felipe S. Rossi, Eduardo L. V. Costa, Letícia Correa, Daniela Iope, Pedro Dalla Pacce, Fabia Martins-Celini, Ayla Bernardes, Maisa Ribeiro, Marcelo B. P. Amato
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
BTK Inhibitors in Cancer Patients with COVID-19: “The Winner Will be the One Who Controls That Chaos” (Napoleon Bonaparte)
Authors: Elise A. Chong, Lindsey E. Roeker, Mazyar Shadman, Matthew S. Davids, Stephen J. Schuster, Anthony R. Mato
Journal: Clinical Cancer Research (2020)

Abstract As the SARS-CoV-2 (COVID-19) pandemic spreads and the number of Bruton's tyrosine kinase inhibitor (BTKi)-treated COVID-19-affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. In favor of BTKi continuation, BTK plays an active role in macrophage polarization. By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with COVID-19. In favor of BTKi discontinuation, we note a potentially increased risk of secondary infections and impaired humoral immunity. We hypothesize that the potential benefit of blunting a hyperinflammatory response to SARS-CoV-2 through attenuation of M1 polarization outweighs the potential risk of impaired humoral immunity, not to mention the risk of rapid progression of B-cell malignancy following BTKi interruption. On the basis of this, we suggest continuing BTKi in patients with COVID-19.
CellMiner: NCI-60細胞株集合における転写および薬物パータンを探索するウェブに基づいたゲノムおよび薬理的ツール一式
Authors: C Reinhold William, Sunshine Margot, Liu Hongfang, Varma Sudhir, W Kohn Kurt, Morris Joel, Doroshow James, Pommier Yves
Journal: Cancer Research (2012)
Characterization of acute acral skin lesions in nonhospitalized patients: A case series of 132 patients during the COVID-19 outbreak
Authors: Diego Fernandez-Nieto, Juan Jimenez-Cauhe, Ana Suarez-Valle, Oscar M. Moreno-Arrones, David Saceda-Corralo, Arantxa Arana-Raja, Daniel Ortega-Quijano
Journal: Journal of the American Academy of Dermatology (2020)
Targeting monoamine oxidase to dampen NLRP3 inflammasome activation in inflammation
Authors: Ricardo Sánchez-Rodríguez, Fabio Munari, Roberta Angioni, Francisca Venegas, Andrielly Agnellini, María Paulette Castro-Gil, Alessandra Castegna, Roberto Luisetto, Antonella Viola, Marcella Canton
Journal: Cellular and Molecular Immunology (2020)
Characteristics of Hospitalized Adults With COVID-19 in an Integrated Health Care System in California
Authors: Laura C. Myers, Stephen M. Parodi, Gabriel J. Escobar, Vincent X. Liu
Journal: JAMA (2020)

This case series characterizes the demographics, health services use, and vital status and discharge dispositions of patients with polymerase chain reaction–confirmed coronavirus disease 2019 (COVID-19) hospitalized in the Kaiser Permanente Northern California health system in March 2020.
Helen Salisbury: No time for decision making
Authors: Helen Salisbury
Journal: BMJ (2020)

The world’s been turned upside down in the past six weeks, and many people’s familiar routines of work, school, family, and friends are gone. Although GPs are not immune, the disruption we face is comparatively mild. We’ve changed our way of working, consulting mostly by phone or video link, but most of us are still going into the surgery and meeting colleagues, albeit at a two metre distance.

Many GPs are also staffing covid clinics in the community, and we’re getting used to donning and doffing masks and aprons. In our practice we had a phase of reorganisation, followed by a strange lull when almost all patient contacts were about coronavirus, and now …
Covid-19: All essential workers in England can now be tested
Authors: Gareth Iacobucci
Journal: BMJ (2020)

All key workers in England and members of their households who are showing symptoms of covid-19 will now be able to get tested for the virus, the government has promised. This widening of access, enabled by an increase in capacity, comes as the government is under pressure to meet its target to carry out 100 000 tests a day by the end of April.

From Friday 24 April a new online system is available for employees in essential roles to book a test for themselves or for members of their household who have symptoms of covid-19. Employers can also register and refer any of their staff who are self-isolating at home.

However, as of mid-morning on Friday the site was …
Therapeutic Efficacy of Immune Stimulatory Thymidine Kinase and fms-like Tyrosine Kinase 3 Ligand (TK/Flt3L) Gene Therapy in a Mouse Model of High-Grade Brainstem Glioma
Authors: Flor Mendez, Padma Kadiyala, Felipe J. Nunez, Stephen Carney, Fernando M. Nunez, Jessica C. Gauss, Ramya Ravindran, Sheeba Pawar, Marta Edwards, Maria Belen Garcia-Fabiani, Santiago Haase, Pedro R. Lowenstein, Maria G. Castro
Journal: Clinical Cancer Research (2020)

Diffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, Activin A receptor type I (ACVR1)-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy.We utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNA-sequencing analysis on neurospheres harboring mACVR1. mACVR1 neurospheres were implanted into the pons of immune-competent mice to test the therapeutic efficacy and toxicity of immune-stimulatory gene therapy using adenoviruses expressing thymidine kinase (TK) and fms-like tyrosine kinase 3 ligand (Flt3L). mACVR1 neurospheres expressing the surrogate tumor antigen ovalbumin were generated to investigate whether TK/Flt3L treatment induces the recruitment of tumor antigen-specific T cells.Histologic analysis of mACVR1 tumors indicates that they are localized in the brainstem and have increased downstream signaling of bone morphogenetic pathway as demonstrated by increased phospho-smad1/5 and Id1 levels. Transcriptome analysis of mACVR1 neurosphere identified an increase in the TGFβ signaling pathway and the regulation of cell differentiation. Adenoviral delivery of TK/Flt3L in mice bearing brainstem gliomas resulted in antitumor immunity, recruitment of antitumor-specific T cells, and increased median survival (MS).This study provides insights into the phenotype and function of the tumor immune microenvironment in a mouse model of brainstem glioma harboring mACVR1. Immune-stimulatory gene therapy targeting the hosts' antitumor immune response inhibits tumor progression and increases MS of mice bearing mACVR1 tumors.