tbuckley/cabot-search huggingface dataset:
Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum
Authors: Paulo Lizano, Olivia Lutz, George Ling, Adam M. Lee, Seenae Eum, Jeffrey R. Bishop, Sinead Kelly, Ofer Pasternak, Brett Clementz, Godfrey Pearlson, John A. Sweeney, Elliot Gershon, Carol Tamminga, Matcheri Keshavan
Journal: American Journal of Psychiatry (2019)

The choroid plexus is an important physiological barrier and produces CSF and neurotrophic, angiogenic, and inflammatory factors involved in brain development. Choroid plexus abnormalities have been implicated in both schizophrenia and bipolar disorder. A previous choroid plexus transcriptomic analysis of schizophrenia identified an upregulation of immune and inflammatory genes that correlated with peripheral inflammatory markers. The purpose of this study was to examine choroid plexus volume in probands across the psychosis spectrum and in their first-degree and axis II cluster A relatives, as well as choroid plexus familiality and choroid plexus covariance with clinical, cognitive, brain, and peripheral marker measures.Choroid plexus volume was quantified (using FreeSurfer) in psychosis probands, their first-degree and axis II cluster A relatives, and healthy control subjects, organized by DSM-IV-TR diagnosis. Analyte, structural connectivity, and genotype data were collected from a subset of study subjects.Choroid plexus volume was significantly larger in probands compared with first-degree relatives or healthy control subjects; first-degree relatives had intermediate enlargement compared with healthy control subjects; and total choroid plexus volume was significantly heritable. Larger volume was associated with worse cognition, smaller total gray matter and amygdala volume, larger lateral ventricle volume, and lower structural connectivity in probands. Associations between larger volume and higher levels of interleukin 6 in probands was also observed.These findings suggest the involvement of the choroid plexus across the psychosis spectrum with a potential pathophysiological mechanism involving the neuroimmune axis, which functions in maintaining brain homeostasis and interacting with the peripheral immune and inflammatory system. The choroid plexus may be an important target in future research.
<i>PD</i>‐<i>L1</i> and <i>PD</i>‐<i>L2</i> expression correlated genes in non‐small‐cell lung cancer
Authors: Trine Vilsbøll Larsen, Dianna Hussmann, Anders Lade Nielsen
Journal: Cancer Communications (2019)

Abstract Background Programmed cell death ligand‐1 (PD‐L1) and ligand‐2 (PD‐L2) interaction with programmed cell death protein‐1 (PD‐1) represent an immune‐inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade‐based immunotherapy in cancer. In non‐small‐cell lung cancer (NSCLC), improved understanding of PD‐1 checkpoint blockade‐responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD ‐ L1 and PD ‐ L2 expression correlated genes in NSCLC. Methods We performed comparative retrospective analyses to identify PD ‐ L1 and PD ‐ L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non‐small‐cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results Analysis of the CCLE dataset Lung_NSC identified expression correlation between PD ‐ L1 and PD ‐ L2 . Moreover, we identified expression correlation between 489 genes and PD ‐ L1 , 191 genes and PD ‐ L2 , and 111 genes for both. PD ‐ L1 and PD ‐ L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD ‐ L1 , 914 genes and PD ‐ L2 , and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD ‐ L1 , 326 genes and PD ‐ L2 , and 13 genes for both. Only a few genes expression correlated with PD ‐ L1 and PD ‐ L2 across the CCLE and TCGA datasets. Expression of Interferon signaling‐involved genes converged in particular with the expression correlated genes for PD ‐ L1 in Lung_NSC, for PD ‐ L2 in LUSC, and for both PD ‐ L1 and PD ‐ L2 in LUAD. In LUSC, PD ‐ L1 , and to a lesser extent PD ‐ L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD ‐ L1 expression. Expression correlation analyses of the PD‐L1 and PD‐L2 receptors programmed cell death protein‐1 (PD‐1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD ‐ 1 and CD80 expression correlated with both PD ‐ L1 and PD ‐ L2 in LUAD. CD80 expression correlated with PD ‐ L2 in LUSC. Conclusions We present gene signatures associated with PD ‐ L1 and PD ‐ L2 mRNA expression in NSCLC which could possess importance in relation to understand PD‐1 checkpoint blockade‐responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy.
Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Multiply Relapsed or Refractory Adult Large B-Cell Lymphoma
Authors: John K. Lin, Lori S. Muffly, Michael A. Spinner, James I. Barnes, Douglas K. Owens, Jeremy D. Goldhaber-Fiebert
Journal: Journal of Clinical Oncology (2019)

Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness.We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty.In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS.At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.
Abstract 16056: LINC00341 Exerts an Anti-Inflammatory Effect on Endothelial Cells by Repressing VCAM1
Authors: Tse-shun Huang, Sara Quon, Phu Nguyen, Yi-Shuan Li, Shankar Subramaniam, John Shyy, Shu Chien
Journal: Circulation (2017)

Introduction: The long non-coding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and...
Trimodal Therapy for Bladder Cancer
Authors: Alexander P. Cole, Quoc-Dien Trinh
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
Progress Toward Measles Elimination — Pakistan, 2000–2018
Authors: Mohammed Osama Mere, James L. Goodson, Arshad K. Chandio, Muhammad Suleman Rana, Quamrul Hasan, Nadia Teleb, James P. Alexander
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In 1997, the 21 countries in the World Health Organization (WHO) Eastern Mediterranean Region* (EMR) passed a resolution during the 41st session of the Regional Committee for the Eastern Mediterranean to eliminate measles† (1). In 2015, this goal was included as a priority in the Eastern Mediterranean Vaccine Action Plan 2016-2020 (2), approved at the 62nd session of the Regional Committee (3). To achieve measles elimination, the WHO Regional Office for the Eastern Mediterranean developed the following four-pronged strategy: 1) achieve ≥95% vaccination coverage with the first dose of measles-containing vaccine (MCV) among children in every district of each country through routine immunization services; 2) achieve ≥95% vaccination coverage with a second MCV dose in every district of each country either through implementation of a routine 2-dose vaccination schedule or through supplementary immunization activities (SIAs)§; 3) conduct high-quality, case-based measles surveillance in all countries; and 4) provide optimal measles clinical case management, including dietary supplementation with vitamin A (4). Pakistan, an EMR country with a population of approximately 200 million, accounts for nearly one third of the overall EMR population. This report describes progress and challenges toward measles elimination in Pakistan during 2000-2018. During the study period, estimated coverage with the first MCV dose (MCV1) increased from 57% in 2000 to 76% in 2017. The second MCV dose (MCV2) was introduced nationwide in 2009, and MCV2 coverage increased from 30% in 2009 to 45% in 2017. During 2000-2018, approximately 232.5 million children received doses of MCV during SIAs. Reported confirmed measles incidence increased from an average of 24.6 per 1 million persons during 2000-2009 to an average of 80.4 during 2010-2018, with peaks in 2013 (230.3) and 2018 (153.6). In 2017 and 2018, the rates of suspected cases discarded as nonmeasles after investigation were 2.1 and 1.5 per 100,000 population, reflecting underreporting of cases. To achieve measles elimination, additional efforts are needed to increase MCV1 and MCV2 coverage, develop strategies to identify and reach communities not accessing immunization services, and increase sensitivity of case-based measles surveillance in all districts.
Benchmark on a large cohort for sleep-wake classification with machine learning techniques
Authors: Joao Palotti, Raghvendra Mall, Michael Aupetit, Michael Rueschman, Meghna Singh, Aarti Sathyanarayana, Shahrad Taheri, Luis Fernandez-Luque
Journal: npj Digital Medicine (2019)

Accurately measuring sleep and its quality with polysomnography (PSG) is an expensive task. Actigraphy, an alternative, has been proven cheap and relatively accurate. However, the largest experiments conducted to date, have had only hundreds of participants. In this work, we processed the data of the recently published Multi-Ethnic Study of Atherosclerosis (MESA) Sleep study to have both PSG and actigraphy data synchronized. We propose the adoption of this publicly available large dataset, which is at least one order of magnitude larger than any other dataset, to systematically compare existing methods for the detection of sleep-wake stages, thus fostering the creation of new algorithms. We also implemented and compared state-of-the-art methods to score sleep-wake stages, which range from the widely used traditional algorithms to recent machine learning approaches. We identified among the traditional algorithms, two approaches that perform better than the algorithm implemented by the actigraphy device used in the MESA Sleep experiments. The performance, in regards to accuracy and F1 score of the machine learning algorithms, was also superior to the device's native algorithm and comparable to human annotation. Future research in developing new sleep-wake scoring algorithms, in particular, machine learning approaches, will be highly facilitated by the cohort used here. We exemplify this potential by showing that two particular deep-learning architectures, CNN and LSTM, among the many recently created, can achieve accuracy scores significantly higher than other methods for the same tasks.
Endoscopic entero-enteral bypass: an effective new approach to the treatment of postsurgical complications of hepaticojejunostomy
Authors: Massimiliano Mutignani, Edoardo Forti, Alberto Larghi, Francesco Pugliese, Marcello Cintolo, Mutaz Massad, Angelo Italia, Alberto Tringali, Giovanni Carlo Ferrari, Andrea De Gasperi, Antonio Rampoldi, Luciano De Carlis, Osvaldo Chiara, Carlo Paparozzi, Lorenzo Dioscoridi
Journal: Endoscopy (2019)

Management of biliary adverse events (BAEs) after biliodigestive anastomosis is challenging. We propose a new endoscopic approach to improve BAEs in this clinical setting.Patients who had BAEs after a hepaticojejunostomy with Roux-en-Y loop or a Whipple procedure underwent creation of an entero-enteral endoscopic bypass (EEEB) between the duodenal/gastric wall and the biliary jejunal loop under endoscopic ultrasound (EUS) and fluoroscopic guidance using specifically designed fully covered self-expandable metal stents.32 consecutive patients underwent EEEB, which was successful in all but one patient. One procedural and five long-term mild adverse events occurred. Endoscopic retrograde cholangiography (ERC) through the EEEB successfully treated all types of BAEs in these patients. Disease recurred in two patients who were successfully re-treated through the EEEB.Our retrospective study showed that in patients with BAEs after biliodigestive anastomosis, EEEB is safe, feasible, and allows a successful long-term treatment of different BAEs in a tertiary referral center with high-level experience in both endoscopic retrograde cholangiopancreatography and EUS.
Autophagy is required for lung development and morphogenesis
Authors: Behzad Yeganeh, Joyce Lee, Leonardo Ermini, Irene Lok, Cameron Ackerley, Martin Post
Journal: Journal of Clinical Investigation (2019)

Bronchopulmonary dysplasia (BPD) remains a major respiratory illness in extremely premature infants. The biological mechanisms leading to BPD are not fully understood, although an arrest in lung development has been implicated. The current study aimed to investigate the occurrence of autophagy in the developing mouse lung and its regulatory role in airway branching and terminal sacculi formation. We found 2 windows of epithelial autophagy activation in the developing mouse lung, both resulting from AMPK activation. Inhibition of AMPK-mediated autophagy led to reduced lung branching in vitro. Conditional deletion of beclin 1 (Becn1) in mouse lung epithelial cells (Becn1Epi-KO), either at early (E10.5) or late (E16.5) gestation, resulted in lethal respiratory distress at birth or shortly after. E10.5 Becn1Epi-KO lungs displayed reduced airway branching and sacculi formation accompanied by impaired vascularization, excessive epithelial cell death, reduced mesenchymal thinning of the interstitial walls, and delayed epithelial maturation. E16.5 Becn1Epi-KO lungs had reduced terminal air sac formation and vascularization and delayed distal epithelial differentiation, a pathology similar to that seen in infants with BPD. Taken together, our findings demonstrate that intrinsic autophagy is an important regulator of lung development and morphogenesis and may contribute to the BPD phenotype when impaired.
Screening for atrial fibrillation: waiting for randomised trial data
Authors: Robert Steele, John Marshall, Anne Mackie
Journal: BMJ (2019)

We agree with Berge that Wilson and Jungner would not approve of screening for atrial fibrillation.1 The key problems are that we do not know whether screen detected atrial fibrillation carries the same risk of stroke as disease that is clinically detected …
Rethinking Cognitive Load: A Default-Mode Network Perspective
Authors: Adrianna C Jenkins
Journal: Trends in Cognitive Sciences (2019)

Typical cognitive load tasks are now known to deactivate the brain's default-mode network (DMN). This raises the possibility that apparent effects of cognitive load could arise from disruptions of DMN processes, including social cognition. Cognitive load studies are reconsidered, with reinterpretations of past research and implications for dual-process theory.
Examining the Frequency of Phlebotomy in Patients with Polycythemia Vera (PV) in the United States: An Analysis of Data from the REVEAL Study
Authors: Ralph V. Boccia, Pedro M. Sanz-Altamira, Khuda Dad Khan, Dmitriy Berenzon, Ellen W. Friedman, Ahmad B. Naim, Dilan Chamikara Paranagama, Ruben A Mesa
Journal: Blood (2017)
Dok3–protein phosphatase 1 interaction attenuates Card9 signaling and neutrophil-dependent antifungal immunity
Authors: Jia Tong Loh, Shengli Xu, Jian Xin Huo, Susana Soo-Yeon Kim, Yue Wang, Kong-Peng Lam
Journal: Journal of Clinical Investigation (2019)

Invasive fungal infection is a serious health threat with high morbidity and mortality. Current antifungal drugs only demonstrate partial success in improving prognosis. Furthermore, mechanisms regulating host defense against fungal pathogens remain elusive. Here, we report that the downstream of kinase 3 (Dok3) adaptor negatively regulates antifungal immunity in neutrophils. Our data revealed that Dok3 deficiency increased phagocytosis, proinflammatory cytokine production, and netosis in neutrophils, thereby enhancing mutant mouse survival against systemic infection with a lethal dose of the pathogenic fungus Candida albicans. Biochemically, Dok3 recruited protein phosphatase 1 (PP1) to dephosphorylate Card9, an essential player in innate antifungal defense, to dampen downstream NF-κB and JNK activation and immune responses. Thus, Dok3 suppresses Card9 signaling, and disrupting Dok3-Card9 interaction or inhibiting PP1 activity represents therapeutic opportunities to develop drugs to combat candidaemia.
Nuclear imaging of liposomal drug delivery systems: A critical review of radiolabelling methods and applications in nanomedicine
Authors: Francis Man, Peter J. Gawne, Rafael T.M. de Rosales
Journal: Advanced Drug Delivery Reviews (2019)

The integration of nuclear imaging with nanomedicine is a powerful tool for efficient development and clinical translation of liposomal drug delivery systems. Furthermore, it may allow highly efficient imaging-guided personalised treatments. In this article, we critically review methods available for radiolabelling liposomes. We discuss the influence that the radiolabelling methods can have on their biodistribution and highlight the often-overlooked possibility of misinterpretation of results due to decomposition in vivo. We stress the need for knowing the biodistribution/pharmacokinetics of both the radiolabelled liposomal components and free radionuclides in order to confidently evaluate the images, as they often share excretion pathways with intact liposomes (e.g. phospholipids, metallic radionuclides) and even show significant tumour uptake by themselves (e.g. some radionuclides). Finally, we describe preclinical and clinical studies using radiolabelled liposomes and discuss their impact in supporting liposomal drug development and clinical translation in several diseases, including personalised nanomedicine approaches.
Abstract 15745: Surgical Ineligibility and Long-term Clinical Outcome in Patients With Severe Coronary Artery Disease: The CREDO-Kyoto Registry Cohort-2
Authors: Yukiko Matsumura-Nakano, Hiroki Shiomi, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Kenji Ando, Kyohei Yamaji, Satoshi Shizuta, Ryuzo Sakata, Michiya Hanyu, Mitsuomi Shimamoto, Noboru Nishiwaki, Tatsuhiko Komiya, Takeshi Kimura
Journal: Circulation (2017)

Introduction: In patients with severe coronary artery disease (triple-vessel disease [3VD] and left main coronary artery disease [ULMCAD]) who require coronary revascularization in the real world c...