tbuckley/cabot-search huggingface dataset:
Palliative Care Consult
Authors: Christopher H. Schifeling
Journal: JAMA (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 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
TCT CONNECT-264 Twelve-Month Clinical Outcomes After Implantation of Long Ultrathin Sirolimus-Eluting Stents With Biodegradable Polymers in Atherosclerotic Coronary Lesions
Authors: Prakash Ajmera, Pothineni Ramesh Babu, Kamal Kumar Chawla, Sai Sudhakar Mantravadi, Pankaj Jariwala, Vinod Vijan, Vikrant Vijan, Anil Potdar, M.K. Inamdar, Abhijit Pathak
Journal: Journal of the American College of Cardiology (2020)
Opposing Influence of Top-down and Bottom-up Input on Excitatory Layer 2/3 Neurons in Mouse Primary Visual Cortex
Authors: Rebecca Jordan, Georg B. Keller
Journal: Neuron (2020)

Processing in cortical circuits is driven by combinations of cortical and subcortical inputs. These inputs are often conceptually categorized as bottom-up, conveying sensory information, and top-down, conveying contextual information. Using intracellular recordings in mouse primary visual cortex, we measured neuronal responses to visual input, locomotion, and visuomotor mismatches. We show that layer 2/3 (L2/3) neurons compute a difference between top-down motor-related input and bottom-up visual flow input. Most L2/3 neurons responded to visuomotor mismatch with either hyperpolarization or depolarization, and the size of this response was correlated with distinct physiological properties. Consistent with a subtraction of bottom-up and top-down input, visual and motor-related inputs had opposing influence on L2/3 neurons. In infragranular neurons, we found no evidence of a difference computation and responses were consistent with positive integration of visuomotor inputs. Our results provide evidence that L2/3 functions as a bidirectional comparator of top-down and bottom-up input.
Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions
Authors: Enrique Navas-Pérez, Cristina Vicente-García, Serena Mirra, Demian Burguera, Noèlia Fernàndez-Castillo, José Luis Ferrán, Macarena López-Mayorga, Marta Alaiz-Noya, Irene Suárez-Pereira, Ester Antón-Galindo, Fausto Ulloa, Carlos Herrera-Úbeda, Pol Cuscó, Rafael Falcón-Moya, Antonio Rodríguez-Moreno, Salvatore D’Aniello, Bru Cormand, Gemma Marfany, Eduardo Soriano, Ángel M. Carrión, Jaime J. Carvajal, Jordi Garcia-Fernàndez
Journal: Genome biology (2020)

Abstract Background One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood. Results Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes. Conclusions We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3 , is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.
Effective interventions for potentially modifiable risk factors for late-onset dementia: a costs and cost-effectiveness modelling study
Authors: Naaheed Mukadam, Robert Anderson, Martin Knapp, Raphael Wittenberg, Maria Karagiannidou, Sergi G Costafreda, Madison Tutton, Charles Alessi, Gill Livingston
Journal: The Lancet Healthy Longevity (2020)

The potential economic value of interventions to prevent late-onset dementia is unknown. We modelled this for potentially modifiable risk factors for dementia.For this modelling study, we searched PubMed and Web of Science from inception to March 12, 2020, and included interventions that: successfully targeted any of nine prespecified potentially modifiable risk factors (hypertension, diabetes, hearing loss, obesity, physical inactivity, social isolation, depression, cigarette smoking, and less childhood education); had robust evidence that the intervention improved risk or risk behaviour; and are feasible to enact in an adult population. We established when in the life course each intervention would be delivered. We calculated dementia incidence reduction from annual incidence of dementia in people with each risk factor, and population attributable fraction for each risk, corrected for risk factor clustering, and how effectively the intervention controls the risk factor. We calculated the discounted value of lifetime health gain and effect on cost (including NHS, social care and carer costs) per person eligible for treatment. We estimated annual total expenditure on the fully operational intervention programme in England.We found effective interventions for hypertension, smoking cessation, diabetes prevention, and hearing loss. Treatments for stopping smoking and provision of hearing aids reduced cost. Treatment of hypertension was cost-effective by reference to standard UK thresholds. The three interventions when fully implemented would save £1·863 billion annually in England, reduce dementia prevalence by 8·5%, and produce quality-adjusted life-year gains. The intervention for diabetes was unlikely to be cost-effective in terms of effect on dementia alone.There is a strong case for implementing the three effective interventions on grounds of cost-effectiveness and quality-of-life gains, as well as for improvements in general health. The interventions have the potential to remain cost-saving or cost-effective even with variations in dementia incidence and costs and effectiveness of interventions.Economic and Social Research Council.
Perforation and bleeding during an underwater endoscopic mucosal resection of a large colonic lesion
Authors: José Luiz Paccos, Daniela Suppo de Oliveira, Fernando J. S. de Oliveira, Eduardo M. A. Pereira Junior, Fernando L. Mota, Mayara M. C. da Silva, Paulo Alberto F. P. Corrêa
Journal: Endoscopy (2020)

Underwater endoscopic mucosal resection (UEMR) is a well-established endoscopic technique for the resection of colorectal lesions in general; it is known to be safe and effective [1]. Water immersion provides a "floating" effect of the mucosa and submucosa, keeping them apart from the muscularis propria and allowing a deep yet safe resection. It has been proved to be cost-effective (in comparison to the standard EMR technique) because it does not require a submucosal injection and is also extremely helpful for resecting large colorectal lesions as well as those with a prominent fibrotic component as seen in recurrent lesions.
Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials
Authors: Willemijn S M E Theelen, Dawei Chen, Vivek Verma, Brian P Hobbs, Heike M U Peulen, Joachim G J V Aerts, Idris Bahce, Anna Larissa N Niemeijer, Joe Y Chang, Patricia M de Groot, Quynh-Nhu Nguyen, Nathan I Comeaux, George R Simon, Ferdinandos Skoulidis, Steven H Lin, Kewen He, Roshal Patel, John Heymach, Paul Baas, James W Welsh
Journal: The Lancet Respiratory Medicine (2020)
Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)
Authors: Anup Agarwal, Aparna Mukherjee, Gunjan Kumar, Pranab Chatterjee, Tarun Bhatnagar, Pankaj Malhotra
Journal: BMJ (2020)

Abstract Objective To investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India. Design Open label, parallel arm, phase II, multicentre, randomised controlled trial. Setting 39 public and private hospitals across India. Participants 464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm). Interventions Participants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study. Main outcome measure Composite of progression to severe disease (PaO 2 /FiO 2 &lt;100 mm Hg) or all cause mortality at 28 days post-enrolment. Results Progression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval −0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54). Conclusion Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19. Trial registration Clinical Trial Registry of India CTRI/2020/04/024775.
Quality and Safety in Health Care, Part LXXXII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Reports from the Institute of Medicine regarding the number of errors in medicine leading to fatalities prompted a major review of medical practices and a move to make medical systems high reliability organizations. Many of the concepts used today to improve performance in health care are borrowed from what has been learned from successes and accidents in other industries, especially in the aviation, space, and nuclear power programs. An emphasis on excellent leadership and communication, the knowledge that there needs to be an emphasis on system failures rather than human failures, and having a safety culture that encourages everyone to be mindful of potential errors and report errors are critical to achieve high reliability.
TCT CONNECT-221 Primary PCI for STEMI During the COVID-19 Pandemic in London: A Systematic Analysis of Pathway Activation and Outcomes
Authors: Callum Little, Richard Jabbour, Tushar Kotecha, Luciano Candilio, Lucy Lawson, Brian Wang, Gavin Manmathan, John Coghlan, Niket Patel, Sundeep Kalra, Tim Lockie, Deven Patel, Elliot Smith, Christopher Baker, Ramzi Khamis, Ghada Mikhail, Iqbal Malik, Roby Rakhit
Journal: Journal of the American College of Cardiology (2020)
Coxsackievirus B Type 4 Infection in β Cells Downregulates the Chaperone Prefoldin URI to Induce a MODY4-like Diabetes via Pdx1 Silencing
Authors: Hugo Bernard, Ana Teijeiro, Almudena Chaves-Pérez, Cristian Perna, Basanthi Satish, Anna Novials, Jennifer P. Wang, Nabil Djouder
Journal: Cell Reports Medicine (2020)

Enteroviruses are suspected to contribute to insulin-producing β cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice and in rat insulinoma cells displays loss of unconventional prefoldin RPB5 interactor (URI) and PDX1, affecting β cell function and identity. Genetic URI ablation in the mouse pancreas causes PDX1 depletion in β cells. Importantly, diabetic PDX1 heterozygous mice overexpressing URI in β cells are more glucose tolerant. Mechanistically, URI loss triggers estrogen receptor nuclear translocation leading to DNA methyltransferase 1 (DNMT1) expression, which induces Pdx1 promoter hypermethylation and silencing. Consequently, demethylating agent procainamide-mediated DNMT1 inhibition reinstates PDX1 expression and protects against diabetes in pancreatic URI-depleted mice . Finally, the β cells of human diabetes patients show correlations between viral protein 1 and URI, PDX1, and DNMT1 levels. URI and DNMT1 expression and PDX1 silencing provide a causal link between enterovirus infection and diabetes.
RNA editing in cancer impacts mRNA abundance in immune response pathways
Authors: Tracey W. Chan, Ting Fu, Jae Hoon Bahn, Hyun-Ik Jun, Jae-Hyung Lee, Giovanni Quinones-Valdez, Chonghui Cheng, Xinshu Xiao
Journal: Genome biology (2020)

RNA editing generates modifications to the RNA sequences, thereby increasing protein diversity and shaping various layers of gene regulation. Recent studies have revealed global shifts in editing levels across many cancer types, as well as a few specific mechanisms implicating individual sites in tumorigenesis or metastasis. However, most tumor-associated sites, predominantly in noncoding regions, have unknown functional relevance.Here, we carry out integrative analysis of RNA editing profiles between epithelial and mesenchymal tumors, since epithelial-mesenchymal transition is a key paradigm for metastasis. We identify distinct editing patterns between epithelial and mesenchymal tumors in seven cancer types using TCGA data, an observation further supported by single-cell RNA sequencing data and ADAR perturbation experiments in cell culture. Through computational analyses and experimental validations, we show that differential editing sites between epithelial and mesenchymal phenotypes function by regulating mRNA abundance of their respective genes. Our analysis of RNA-binding proteins reveals ILF3 as a potential regulator of this process, supported by experimental validations. Consistent with the known roles of ILF3 in immune response, epithelial-mesenchymal differential editing sites are enriched in genes involved in immune and viral processes. The strongest target of editing-dependent ILF3 regulation is the transcript encoding PKR, a crucial player in immune and viral response.Our study reports widespread differences in RNA editing between epithelial and mesenchymal tumors and a novel mechanism of editing-dependent regulation of mRNA abundance. It reveals the broad impact of RNA editing in cancer and its relevance to cancer-related immune pathways.
Prolonged adaptive immune activation in COVID-19: implications for maintenance of long-term immunity?
Authors: Philip A. Mudd, Kenneth E. Remy
Journal: Journal of Clinical Investigation (2020)

Ongoing observational clinical research has prioritized understanding the human immune response to SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. Several recent studies suggest that immune dysregulation with early and prolonged adaptive immune system activation can result in cellular exhaustion. In this issue of the JCI, Files et al. compared cellular immune phenotypes during the first two months of COVID-19 in hospitalized and less severe, non-hospitalized patients. The authors utilized flow cytometry to analyze circulating peripheral blood mononuclear cells. Both patient cohorts maintained B and T cell phenotypes consistent with activation and cellular exhaustion throughout the first two months of infection. Additionally, follow-up samples from the non-hospitalized patient cohort showed that activation markers and cellular exhaustion increased over time. These findings illustrate the persistent nature of the adaptive immune system changes that have been noted in COVID-19 and suggest longer term effects that may shape the maintenance of immunity to SARS-CoV-2.
Autofluorescence Imaging of 3D Tumor–Macrophage Microscale Cultures Resolves Spatial and Temporal Dynamics of Macrophage Metabolism
Authors: Tiffany M. Heaster, Mouhita Humayun, Jiaquan Yu, David J. Beebe, Melissa C. Skala
Journal: Cancer Research (2020)

Macrophages within the tumor microenvironment (TME) exhibit a spectrum of protumor and antitumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to nondestructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models. Fluorescence lifetimes and intensities of NAD(P)H and FAD were acquired at 24, 48, and 72 hours poststimulation for mouse macrophages (RAW264.7) stimulated with IFNγ or IL4 plus IL13 in 2D culture, confirming that autofluorescence measurements capture known metabolic phenotypes. To quantify metabolic dynamics of macrophages within the TME, mouse macrophages or human monocytes (RAW264.7 or THP-1) were cultured alone or with breast cancer cells (mouse polyoma-middle T virus or primary human IDC) in 3D microfluidic platforms. Human monocytes and mouse macrophages in tumor cocultures exhibited significantly different FAD mean lifetimes and greater migration than monocultures at 24, 48, and 72 hours postseeding. In cocultures with primary human cancer cells, actively migrating monocyte-derived macrophages had greater redox ratios [NAD(P)H/FAD intensity] compared with passively migrating monocytes at 24 and 48 hours postseeding, reflecting metabolic heterogeneity in this subpopulation of monocytes. Genetic analyses further confirmed this metabolic heterogeneity. These results establish label-free autofluorescence imaging to quantify dynamic metabolism, polarization, and migration of macrophages at single-cell resolution within 3D microscale models. This combined culture and imaging system provides unique insights into spatiotemporal tumor-immune cross-talk within the 3D TME. SIGNIFICANCE: Label-free metabolic imaging and microscale culture technologies enable monitoring of single-cell macrophage metabolism, migration, and function in the 3D tumor microenvironment.
Characterization of conjunctival microbiome dysbiosis associated with allergic conjunctivitis
Authors: Qiaoxing Liang, Jing Li, Shiyao Zhang, Yinglin Liao, Shixin Guo, Juanran Liang, Xiuli Deng, Yu Liu, Bin Zou, Xiaofeng Wen, Lingyi Liang, Lai Wei
Journal: Allergy (2020)

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Liver Injury Increases the Incidence of HCC following AAV Gene Therapy in Mice
Authors: Dhwanil A. Dalwadi, Laura Torrens, Jordi Abril-Fornaguera, Roser Pinyol, Catherine Willoughby, Jeffrey Posey, Josep M. Llovet, Christian Lanciault, David W. Russell, Markus Grompe, Willscott E. Naugler
Journal: Molecular Therapy (2020)

Adeno-associated virus (AAV) integrates into host genomes at low frequency, but when integration occurs in oncogenic hotspots it can cause hepatocellular carcinoma (HCC). Given the possibility of recombinant AAV (rAAV) integration leading to HCC, common causes of liver inflammation like non-alcoholic fatty liver disease (NAFLD) may increase the risk of rAAV-induced HCC. A rAAV targeting the oncogenic mouse Rian locus was used, and as expected led to HCC in all mice infected as neonates, likely due to growth-related hepatocyte proliferation in young mice. Mice infected with rAAV as adults did not develop HCC unless they were fed a diet leading to NAFLD, with increased inflammation and hepatocyte proliferation. Female mice were less susceptible to rAAV-induced HCC, and male mice with NAFLD treated with estrogen exhibited less inflammation and immune exhaustion associated with oncogenesis compared to those without estrogen. Adult NAFLD mice infected with a non-targeted control rAAV also developed HCC, though only half as frequently as those exposed to the Rian targeted rAAV. This study shows that adult mice exposed to rAAV gene therapy in the context of chronic liver disease developed HCC at high frequency, and thus warrants further study in humans given the high prevalence of NAFLD in the population. Adeno-associated virus (AAV) integrates into host genomes at low frequency, but when integration occurs in oncogenic hotspots it can cause hepatocellular carcinoma (HCC). Given the possibility of recombinant AAV (rAAV) integration leading to HCC, common causes of liver inflammation like non-alcoholic fatty liver disease (NAFLD) may increase the risk of rAAV-induced HCC. A rAAV targeting the oncogenic mouse Rian locus was used, and as expected led to HCC in all mice infected as neonates, likely due to growth-related hepatocyte proliferation in young mice. Mice infected with rAAV as adults did not develop HCC unless they were fed a diet leading to NAFLD, with increased inflammation and hepatocyte proliferation. Female mice were less susceptible to rAAV-induced HCC, and male mice with NAFLD treated with estrogen exhibited less inflammation and immune exhaustion associated with oncogenesis compared to those without estrogen. Adult NAFLD mice infected with a non-targeted control rAAV also developed HCC, though only half as frequently as those exposed to the Rian targeted rAAV. This study shows that adult mice exposed to rAAV gene therapy in the context of chronic liver disease developed HCC at high frequency, and thus warrants further study in humans given the high prevalence of NAFLD in the population.
TCT CONNECT-363 To Assess the Newer Inflammatory Markers in Takayasu’s Arteritis and to Determine the Correlation of Markers With Disease Activity
Authors: Antony Pathadan, Sanjay Tyagi, Mohit Dayal Gupta, Girish Meenahalli Palleda, Ankit Bansal
Journal: Journal of the American College of Cardiology (2020)
Preoperative Opioid Use and Mortality After Minor Outpatient Surgery
Authors: Katherine B. Santosa, Yen-Ling Lai, Jeremie D. Oliver, Hsou-Mei Hu, Chad M. Brummett, Michael J. Englesbe, Jennifer F. Waljee
Journal: JAMA Surgery (2020)

This study evaluates the risk of preoperative opioid exposure on all-cause mortality after outpatient surgery.