tbuckley/cabot-search huggingface dataset:
Cognitive representations and the predictive brain depend heavily on the environment
Authors: Klaus Fiedler
Journal: Behavioral and Brain Sciences (2020)

In their scholarly target article, Gilead et al. explain how abstract mental representations and the predictive brain enable prospection and time-traveling. However, their exclusive focus on intrapsychic capacities misses an important point, namely, the degree to which mind and brain are tuned by the environment. This neglected aspect of adaptive cognition is discussed and illustrated from a cognitive-ecological perspective.
NHS health checks should start at age 25 for BAME patients, MPs hear
Authors: Adrian O’Dowd
Journal: BMJ (2020)

NHS health checks should start at age 25 for BAME patients, MPs hear Adrian O'DowdThe NHS could help prevent illness and reduce the risk of contracting the coronavirus in patients from black, Asian, and minority ethnic (BAME) backgrounds by lowering the age at which the NHS health check begins for some patients, MPs have been told.
Opportunities and Challenges in Using Social Media in Organ Donation
Authors: John O. O. Ayorinde, Kourosh Saeb-Parsy, Ayaz Hossain
Journal: JAMA Surgery (2020)

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A Case of Localized Malignant Peritoneal Mesothelioma With Lung Cancer Detected by 18F-FDG PET/CT
Authors: Shotaro Kobayashi Shimizu, Terue Okamura, Koichi Koyama, Hirotaka Seura, Norifumi Nishida
Journal: Clinical Nuclear Medicine (2020)

Abstract A 62-year-old woman was referred for cough and lower abdominal pain. 18 F-FDG PET/CT showed strong uptake not only in the left lung mass and hilar and mediastinal lymph nodes, but also a huge lower abdominal mass. All lesions were initially thought to be multiple metastases because bronchial biopsy of the lung mass showed poorly differentiated adenocarcinoma. However, the abdominal mass was found to be malignant peritoneal mesothelioma after surgical resection. It was difficult to diagnose this case correctly before resection because localized malignant peritoneal mesothelioma is rare.
SARS-CoV-2 Positivity Rate for Latinos in the Baltimore–Washington, DC Region
Authors: Diego A. Martinez, Jeremiah S. Hinson, Eili Y. Klein, Nathan A. Irvin, Mustapha Saheed, Kathleen R. Page, Scott R. Levin
Journal: JAMA (2020)

Ukachi N. Emeruwa, MD, MPH; Samsiya Ona, MD; Jeffrey L. Shaman, PhD; Amy Turitz, MD; Jason D. Wright, MD; Cynthia Gyamfi-Bannerman, MD, MSc; Alexander Melamed, MD, MPH
Nocturnal Oxygen for High Altitude Travel in Patients With Chronic Obstructive Pulmonary Disease
Authors: Daniel Combs, Sairam Parthasarathy
Journal: JAMA Network Open (2020)

Lu Tan, MD; Tsogyal D. Latshang, MD; Sayaka S. Aeschbacher, MD; Fabienne Huber, MD; Deborah Flueck, MD; Mona Lichtblau, MD; Stefanie Ulrich, MD; Elisabeth D. Hasler, MD; Philipp M. Scheiwiller, MD; Silvia Ulrich, MD; Konrad E. Bloch, MD; Michael Furian, PhD
Abstract B52: Standardized exosome isolation and profiling for biomarker discovery
Authors: Ahmed Fadiel, Nirmal Sharma, Matthew L. Anderson
Journal: Clinical Cancer Research (2020)

Abstract The discovery of an early detection biomarker for advancing disease like cancer is one of the major diagnostic challenges in medicine. Exosomes are microvesicles that are secreted by almost all cells and contain a cargo of DNA, RNA, and/or protein that is not only characteristic of their cell of origin but also capable of functionally impacting target cells and tissues. In this study, we utilized two sources of liquid biopsy to isolate and profile exosomes and perform molecular profiling potential relevant to cancer diagnostics. Using differential immuno-electron and atomic force microscopy, we have identified multiple structurally distinct subtypes of microvesicles and exosomes present in bronchial washings. We have also characterized the patterns of protein contained biomarkers associated with the unique class of exosomes identified in pulmonary washings. We have been able to identify at least three potential biomarkers potentially diagnostic of lung cancer from exosomes obtained with bronchial lavage. Lastly, we have used a bioinformatic approach to simulate potential functional networks of protein-protein interactions and determine how these protein cargoes of pulmonary exosomes impact adjacent pulmonary tissues and determine whether protein expression in specific subtypes of exosomes provides a predictive model of the current cancer state, remotely. Our results led us to conclude that the isolation of exosomes from liquid biopsy offers enormous potential to improve the diagnostic and prognostic capacity of liquid biopsy and their promise to revolutionize diagnostic medicine. Citation Format: Ahmed Fadiel, Nirmal Sharma, Matthew L. Anderson. Standardized exosome isolation and profiling for biomarker discovery [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B52.
An Agonistic Anti-CD137 Antibody Disrupts Lymphoid Follicle Structure and T-Cell-Dependent Antibody Responses
Authors: Jun P. Hong, Glennys V. Reynoso, Prabhakar S. Andhey, Amanda Swain, Jackson S. Turner, Adrianus C.M. Boon, Florian Krammer, Ali H. Ellebedy, Fabio Zanini, Maxim Artyomov, Heather D. Hickman, Michael S. Diamond
Journal: Cell Reports Medicine (2020)

CD137 is a costimulatory receptor expressed on natural killer cells, T cells, and subsets of dendritic cells. An agonistic monoclonal antibody (mAb) against CD137 has been used to reduce tumor burden or reverse autoimmunity in animal models and clinical trials. Here, we show that mice treated with an agonistic anti-CD137 mAb have reduced numbers of germinal center (GC) B cells and follicular dendritic cells (FDCs) in lymphoid tissues, which impair antibody responses to multiple T-cell-dependent antigens, including infectious virus, viral proteins, and conjugated haptens. These effects are not due to enhanced apoptosis or impaired proliferation of B cells but instead correlate with changes in lymphoid follicle structure and GC B cell dispersal and are mediated by CD137 signaling in CD4+ and CD8+ T cells. Our experiments in mice suggest that agonistic anti-CD137 mAbs used in cancer and autoimmunity therapy may impair long-term antibody and B cell memory responses.
Validation of Brief Screening Tools to Identify Impaired Driving Among Older Adults in Australia
Authors: Kaarin J. Anstey, Ranmalee Eramudugolla, Md Hamidul Huque, Mark Horswill, Kim Kiely, Alex Black, Joanne Wood
Journal: JAMA Network Open (2020)

<h3>Importance</h3> There is an urgent need to develop evidence-based assessments to identify older individuals who may be unsafe drivers. <h3>Objective</h3> To validate 8 off-road brief screening tests to predict on-road driving ability and to identify which combination of these provides the best prediction of older adults who will not pass an on-road driving test. <h3>Design, Setting, and Participants</h3> This prognostic study was conducted between October 31, 2013, and May 10, 2017, using the criterion standard for screening tests, an on-road driving test, with analysis conducted from August 1, 2019, to April 2, 2020. A volunteer sample of older drivers was recruited from community advertisements, rehabilitation and driver assessment clinics, and an optometry clinic in Canberra and Brisbane, Australia. <h3>Exposures</h3> Off-road driver screening measures, including the Useful Field of View, DriveSafe/DriveAware, Multi-D battery, Trails B, maze test, Hazard Perception Test, DriveSafe Intersection test, and 14-item Road Law test. <h3>Main Outcomes and Measures</h3> Classification as unsafe on a standardized 50-minute on-road driving assessment administered by a driving instructor and an occupational therapist masked to the participant’s clinical diagnosis and off-road test performance. <h3>Results</h3> A total of 560 drivers aged 63 to 94 years (mean [SD] age, 74.7 [6.2] years]; 350 [62.5%] men) were assessed. Logistic regression and receiver operating characteristic analyses indicated the area under the curve was largest for a multivariate model comprising the Multi-D, Useful Field of View, and Hazard Perception Test, with an area under the curve of 0.89 (95% CI, 0.85-0.94), sensitivity of 80.4%, and specificity of 84.1% for predicting unsafe drivers. The Multi-D battery was the most accurate individual assessment and had an area under the curve of 0.85 (95% CI, 0.79-0.90), sensitivity of 77.1%, and specificity of 82.1%. The multivariate model had sensitivity of 83.3% and specificity of 91.8% in the cognitively impaired group and sensitivity of 87.5% and specificity of 70.8% in the visually impaired group. <h3>Conclusions and Relevance</h3> These findings suggest that off-road screening tests can reliably identify older drivers with a strong probability of failing an on-road driving test. Implementation of these measures could enable better targeting of resources for managing older driver licensing and support injury prevention strategies in this group.
Use of an electronic decision support tool to reduce polypharmacy in elderly people with chronic diseases: cluster randomised controlled trial
Authors: Anja Rieckert, David Reeves, Attila Altiner, Eva Drewelow, Aneez Esmail, Maria Flamm, Mark Hann, Tim Johansson, Renate Klaassen-Mielke, Ilkka Kunnamo, Christin Löffler, Giuliano Piccoliori, Christina Sommerauer, Ulrike S Trampisch, Anna Vögele, Adrine Woodham, Andreas Sönnichsen
Journal: BMJ (2020)

Abstract Objective To evaluate the effects of a computerised decision support tool for comprehensive drug review in elderly people with polypharmacy. Design Pragmatic, multicentre, cluster randomised controlled trial. Setting 359 general practices in Austria, Germany, Italy, and the United Kingdom. Participants 3904 adults aged 75 years and older using eight or more drugs on a regular basis, recruited by their general practitioner. Intervention A newly developed electronic decision support tool comprising a comprehensive drug review to support general practitioners in deprescribing potentially inappropriate and non-evidence based drugs. Doctors were randomly allocated to either the electronic decision support tool or to provide treatment as usual. Main outcome measures The primary outcome was the composite of unplanned hospital admission or death by 24 months. The key secondary outcome was reduction in the number of drugs. Results 3904 adults were enrolled between January and October 2015. 181 practices and 1953 participants were assigned to electronic decision support (intervention group) and 178 practices and 1951 participants to treatment as usual (control group). The primary outcome (composite of unplanned hospital admission or death by 24 months) occurred in 871 (44.6%) participants in the intervention group and 944 (48.4%) in the control group. In an intention-to-treat analysis the odds ratio of the composite outcome was 0.88 (95% confidence interval 0.73 to 1.07; P=0.19, 997 of 1953 v 1055 of 1951). In an analysis restricted to participants attending practice according to protocol, a difference was found favouring the intervention (odds ratio 0.82, 95% confidence interval 0.68 to 0.98; 774 of 1682 v 873 of 1712, P=0.03). By 24 months the number of prescribed drugs had decreased in the intervention group compared with control group (uncontrolled mean change −0.42 v 0.06: adjusted mean difference −0.45, 95% confidence interval −0.63 to −0.26; P&lt;0.001). Conclusions In intention-to-treat analysis, a computerised decision support tool for comprehensive drug review of elderly people with polypharmacy showed no conclusive effects on the composite of unplanned hospital admission or death by 24 months. Nonetheless, a reduction in drugs was achieved without detriment to patient outcomes. Trial registration Current Controlled Trials ISRCTN10137559 .
心疾患:Ca2+緩衝を遅延させることをねらって設計された非典型的EFハンドモチーフは心機能を増強する
Authors: Wang Wang, Barnabei Matthew S, Asp Michelle L, Heinis Frazer I, Arden Erik, Davis Jennifer, Metzger Joseph M, Braunlin Elizabeth, Li Qi, Potter James D, Davis Jonathan P
Journal: Nature Medicine (2013)
Abstract PR09: Frequency and etiology of ctDNA-positive metastatic prostate cancer with BRCA2, ATM, or CDK12 mutations
Authors: Evan Warner, Steven Yip, Matti Annala, Gang Wang, Arkhjamil Angeles, Arshia Beigi, Elena Schönlau, Amanda Wong, Sinja Taavitsainen, Gillian Vandekerkhove, Kevin Beja, Matti Nykter, Daniel Khalaf, Kim Chi, Alexander Wyatt
Journal: Clinical Cancer Research (2020)

Abstract Recent sequencing efforts have shown that genomic alterations within DNA damage repair (DDR) pathways are relatively common in metastatic prostate cancer (mPCa). Patients harboring DDR gene aberrations can respond poorly to standard-of-care androgen receptor (AR)-targeted therapy, potentially because defective DNA repair enables rapid tumor evolution. Research has shown that DDR-deficient mPCa is often genetically unstable due to its high mutation frequency; however, the specific differences in mutations and copy number alterations between DDR mutant and nonmutant tumors have not been established. We performed targeted next-generation sequencing on 1,214 cell-free DNA samples from 718 patients with mPCa. In 30 patients with disruption of BRCA2, ATM, or CDK12, we also sequenced archival primary tumor tissue. 118 patients had a deleterious germline or somatic mutation in at least one of the 22 DDR genes on our targeted panel. The most commonly altered were BRCA2 (n=41), ATM (n=20), and CDK12 (n=21), together present in ~14% of patients. Disruption of the intact second allele was detected in 96%, 82%, and 84% of patients with mutations in BRCA2, ATM, and CDK12, respectively. Patients with a mutation in any one of these genes had fewer mutations in TP53 than a control cohort of DDR-intact patients (p&amp;lt;0.05). However, BRCA2-defective patients had frequent compound deletions of tumor-suppressor genes (TP53, PTEN, RB1). In patients with CDK12 mutations, PTEN or RB1 deletion was rare and samples instead exhibited copy number gains of MDM2 and/or CCND1. ATM-deficient cases did not demonstrate the same degree of genomic instability as either BRCA2- or CDK12-defective disease. In summary, patients with BRCA2, ATM, or CDK12 gene disruption possess distinct patterns of genomic alterations. These findings might help clarify why some DDR-deficient mPCa cases represent a more aggressive disease subtype with a poor response to AR-targeted therapy. This abstract is also being presented as Poster A36. Citation Format: Evan Warner, Steven Yip, Matti Annala, Gang Wang, Arkhjamil Angeles, Arshia Beigi, Elena Schönlau, Amanda Wong, Sinja Taavitsainen, Gillian Vandekerkhove, Kevin Beja, Matti Nykter, Daniel Khalaf, Kim Chi, Alexander Wyatt. Frequency and etiology of ctDNA-positive metastatic prostate cancer with BRCA2, ATM, or CDK12 mutations [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr PR09.
Economic recovery plan should be linked with achieving net zero, says citizens’ assembly
Authors: Jacqui Wise
Journal: BMJ (2020)

The government should link economic recovery with measures that help achieve the target of net zero emissions as the UK emerges from lockdown, a citizens’ assembly has said.

An interim briefing1 from the Climate Assembly UK suggests the government should limit or put conditions on investment in high carbon industries, rethink and invest in infrastructure, and support low carbon industries.

There was also consensus that the government and employers should take steps to encourage lifestyles that …
Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study
Authors: Qin-Long Jing, Ming-Jin Liu, Zhou-Bin Zhang, Li-Qun Fang, Jun Yuan, An-Ran Zhang, Natalie E Dean, Lei Luo, Meng-Meng Ma, Ira Longini, Eben Kenah, Ying Lu, Yu Ma, Neda Jalali, Zhi-Cong Yang, Yang Yang
Journal: The Lancet Infectious Diseases (2020)
Abstract A49: Viable circulating ensembles of tumor-associated cells persist in pretreated patients with solid organ cancers showing no radiologically detectable disease
Authors: Sewanti A. Limaye, Timothy Crook, Dadasaheb Akolkar, Darshana Patil, Pradip Devhare, Revati Patil, Shoeb Patel, Shabista Khan, Raja Dhasarathan, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar
Journal: Clinical Cancer Research (2020)

Abstract The success of treatment in solid organ cancers is ascertained by radiologic imaging as per standard-of-care protocol, with PET-CT being the modality of choice. However, even in cases where complete resolution of the disease is noted radiologically, recurrence or emergence of new metastases is not uncommon. To explore the underlying cause of such recurrence, we hypothesized that circulating metastatic disease (CMD) in the nature of viable tumor cells or clusters would be a persistent systemic feature of solid organ cancers, although there may be no overt evidence of disease. We identified 1,217 patients with known and previously treated cases of various solid organ cancers (metastatic and nonmetastatic), where a recent PET-CT scan showed no radiologic evidence of disease. 15 mL peripheral blood was collected from these patients. Peripheral blood mononuclear cells (PBMCs) were harvested by centrifugation. Circulating ensembles of tumor-associated cells (C-ETACs) were enriched from PBMCs using an epigenetically acting stabilization process, which is cytotoxic towards nonmalignant cells but confers survival privilege on apoptosis-resistant cells of tumorigenic origin as well as their heterotypic clusters (C-ETACs). C-ETACs were characterized by immunostaining for EpCAM, pan-CK, and CD45 as well as for organ-specific markers. Among the 1,217 patients with no radiologic evidence of disease, C-ETACs were detected in 1,118 (91.9%) and were confirmed by immunostaining. In a subset analysis, C-ETACs from 80 samples were immunostained for organ- or subtype-specific antigens including those from head and neck (P63), breast (GCDFP15), colorectum (CDX2), liver (Hep Par-1), ovary (CA125), prostate (PSMA), cervical (P63), and lung (TTF-1/Napsin-A). Circulating metastatic disease (CMD) in the form of viable C-ETACs is a potent threat in patients with solid organ cancers despite complete radiologic response to treatment. Citation Format: Sewanti A. Limaye, Timothy Crook, Dadasaheb Akolkar, Darshana Patil, Pradip Devhare, Revati Patil, Shoeb Patel, Shabista Khan, Raja Dhasarathan, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. Viable circulating ensembles of tumor-associated cells persist in pretreated patients with solid organ cancers showing no radiologically detectable disease [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A49.
Abstract A47: Circulating tumor cell-defined minimal residual disease in locally advanced rectal cancer treated with multimodality therapy
Authors: Lucas Lee, Carol Hall, Antony Lucci, Brian Bednarski, Miguel Rodriguez-Bigas, George Chang, Y. Nancy You
Journal: Clinical Cancer Research (2020)

Abstract Background: Current treatment for locally advanced rectal cancer (LARC) includes multimodality therapy in the neoadjuvant and adjuvant settings. Response to neoadjuvant therapy (NT) is prognostic of long-term outcomes. While long-course chemoradiation (CRT) had been the traditional NT regimen, novel regimens adding systemic therapy and/or eliminating radiation have been introduced. We examined if circulating tumor cells provide prognostic information independent of the specific treatment regimen utilized. Specifically, we aimed to define the significance of CTC-defined minimal residual disease (MRD) in LARC. Methods: A prospective longitudinal protocol enrolled LARC patients (N=100; clinical stage II=4; stage III=96) undergoing NT. Peripheral blood was collected at baseline (t1, treatment-naive), after NT (t2, intraoperatively before tumor manipulation), after resection (t3, 2-8 weeks postoperatively), and after completion of adjuvant therapy (t4, 2-12 weeks after completion). CTC was enumerated by the CellSearch® platform within 72 hours of collection. Patients were followed for disease-free survival (DFS). Results: At t1, CTCs were detected in 28/90 (31.1%) patients with available samples with a median CTC count of 1.5 [IQR: 1.0, 2.75]. NT consisted of long-course pelvic CRT (65%), extended NT with systemic chemotherapy and long- or short-course pelvic CRT (22%), and a radiation-sparing regimen with systemic chemotherapy only (13%). At t2, CTCs were detected in 34/75 (45.3%) patients with a median CTC count of 1 [IQR: 1, 1]. Type of NAT did not correlate with CTC positivity (p=0.637). Ten (9.4%) patients declined surgery, while cPR occurred in 12/93 (12.9%) surgical patients. Postoperatively (t3), CTC was detected in 12/47 (25.5%) patients, with a median count of 1.5 (IQR: 1.0-3.0). After completing adjuvant chemotherapy (t4), only 3/29 (10.3%) patients had detectable CTC. With a median follow-up of 47.50 months from diagnosis for the entire cohort, CTC positivity at t4 significantly stratified DFS (p=0.035). Conclusions: One third of locally advanced RC patients harbored detectable CTCs at baseline. CTC detection after completion of curative-intent multimodality therapy (i.e., MRD) correlated with long-term DFS. Citation Format: Lucas Lee, Carol Hall, Antony Lucci, Brian Bednarski, Miguel Rodriguez-Bigas, George Chang, Y. Nancy You. Circulating tumor cell-defined minimal residual disease in locally advanced rectal cancer treated with multimodality therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A47.
Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer
Authors: Luisa F. Escobar-Hoyos, Alex Penson, Ram Kannan, Hana Cho, Chun-Hao Pan, Rohit K. Singh, Lisa H. Apken, G. Aaron Hobbs, Renhe Luo, Nicolas Lecomte, Sruthi Babu, Fong Cheng Pan, Direna Alonso-Curbelo, John P. Morris, Gokce Askan, Olivera Grbovic-Huezo, Paul Ogrodowski, Jonathan Bermeo, Joseph Saglimbeni, Cristian D. Cruz, Yu-Jui Ho, Sharon A. Lawrence, Jerry P. Melchor, Grant A. Goda, Karen Bai, Alessandro Pastore, Simon J. Hogg, Srivatsan Raghavan, Peter Bailey, David K. Chang, Andrew Biankin, Kenneth R. Shroyer, Brian M. Wolpin, Andrew J. Aguirre, Andrea Ventura, Barry Taylor, Channing J. Der, Daniel Dominguez, Daniel Kümmel, Andrea Oeckinghaus, Scott W. Lowe, Robert K. Bradley, Omar Abdel-Wahab, Steven D. Leach
Journal: Cancer Cell (2020)