tbuckley/cabot-search huggingface dataset:
Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study
Authors: Minggui Wang, Michelle Earley, Liang Chen, Blake M Hanson, Yunsong Yu, Zhengyin Liu, Soraya Salcedo, Eric Cober, Lanjuan Li, Souha S Kanj, Hainv Gao, Jose M Munita, Karen Ordoñez, Greg Weston, Michael J Satlin, Sandra L Valderrama-Beltrán, Kalisvar Marimuthu, Martin E Stryjewski, Lauren Komarow, Courtney Luterbach, Steve H Marshall, Susan D Rudin, Claudia Manca, David L Paterson, Jinnethe Reyes, Maria V Villegas, Scott Evans, Carol Hill, Rebekka Arias, Keri Baum, Bettina C Fries, Yohei Doi, Robin Patel, Barry N Kreiswirth, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Cesar A Arias, David van Duin, Lilian M Abbo, Deverick J Anderson, Rebekka Arias, Cesar A Arias, Keri Baum, Robert A Bonomo, Henry F Chambers, Liang Chen, Kean Lee Chew, Eric Cober, Heather R Cross, Partha Pratim De, Samit Desai, Sorabh Dhar, Valentina Di Castelnuovo, Lorena Diaz, AN Q Dinh, Yohei Doi, Michelle Earley, Brandon Eilertson, Beth Evans, Scott Evans, Vance G Fowler Jr, Bettina C Fries, Hainv Gao, Julia Garcia-Diaz, Omai B Garner, Kerryl Greenwood-Quaintance, Blake Hanson, Erica Herc, Carol Hill, Jesse T Jacob, Jianping Jiang, Robert C Kalayjian, Souha S Kanj, Keith S Kaye, Angela Kim, Lauren Komarow, Barry N Kreiswirth, Courtney Lauterbach, Lanjuan Li, Zhengyin Liu, Claudia Manca, Kalisvar Marimuthu, Steven H Marshall, Todd McCarty, Jose Munita, Oon Tek Ng, Jose Millan Oñate Gutierrez, Karen Ordoñez, Robin Patel, David L Paterson, Anton Peleg, Jinnethe Reyes, Susan D Rudin, Robert A Salata, Soraya Salcedo, Michael J Satlin, Suzannah Schmidt-Malan, Nares Smitasin, Maria Spencer, Martin Stryjewski, Jiachun Su, Paul Ananth Tambyah, Sandra Valderrama, David van Duin, Maria Virginia Villegas Botero, Minggui Wang, Mary Waters, Greg Weston, Darren Wong, Glenn Wortmann, Yang Yang, Yunsong Yu, Fujie Zhang
Journal: The Lancet Infectious Diseases (2021)
Monoclonal Gammopathy of Undetermined Significance and COVID-19: Results from the Population-Based Iceland Screens Treats or Prevents Multiple Myeloma Study (iStopMM)
Authors: Sæmundur Rögnvaldsson, Elias Eythorsson, Sigrun Thorsteinsdottir, Brynjar Vidarsson, Pall Torfi Onundarson, Bjarni Agnar Agnarsson, Margret Sigurdardottir, Ingunn Thorsteinsdottir, Isleifur Olafsson, Hrafnhildur Linnet Runolfsdottir, Dadi Helgason, Arna Emilsdóttir, Aron H Bjornsson, Gudrun Kristjansdottir, Asdis Rosa Thordardottir, Olafur Skuli Indridason, Asbjorn Jonsson, Gauti Kjartan Gislason, Andri Olafsson, Hlif Steingrimsdottir, Petros Kampanis, Malin Hultcrantz, Brian G.M. Durie, Stephen Harding, Ola Landgren, Thorvardur Jon Love, Runolfur Palsson, Sigurdur Y Kristinsson
Journal: Blood (2021)
Overcrowding and long delays in A&amp;E caused over 4000 deaths last year in England, analysis shows
Authors: Gareth Iacobucci
Journal: BMJ (2021)

England had at least 4519 excess deaths in England in 2020-21 as a result of overcrowding and stays of 12 hours or longer in emergency departments, an analysis by the Royal College of Emergency Medicine has found.

The findings are given in a new report from the college into the extent of harm that crowding causes.1

The mortality figure was calculated from findings from the NHS’s Getting It Right First Time (GIRFT) programme, which found that one in 67 patients staying in an emergency department for 12 hours came to excess harm, and hospital episode statistics (for 2020-21), which measure numbers of stays of 12 hours …
IFNγ Signaling in Natural and Therapy-Induced Antitumor Responses
Authors: Alex Martínez-Sabadell, Enrique J. Arenas, Joaquín Arribas
Journal: Clinical Cancer Research (2021)

Abstract IFNγ is a cytokine produced by a restricted number of immune cells that acts on every nucleated cell type. Consistent with this remarkably wide spectrum of targets, the effects of IFNγ are highly pleiotropic. On cells of the immune system, IFNγ signaling has generally a pro-inflammatory effect, coordinating the innate and adaptive responses. On nonimmune cells, IFNγ tends to exert the opposite effect; it inhibits cell proliferation, induces cell death, and, in addition, promotes their recognition by the immune system. These effects on the immune and nonimmune compartments play a crucial role during the immunoediting of tumors and, as shown by recent reports, also determine the efficacy of certain immunotherapies. Different therapeutic interventions to target IFNγ signaling are currently under way, and the emerging picture indicates that rewiring IFNγ signaling, disrupted in some cancer cells, may be an efficacious antitumor therapeutic strategy.
Exploiting LY3009120 and Asciminib Combination to Target TKI-Resistant CML
Authors: Milad Rouhimoghadam, Anthony D. Pomicter, Alexandria Van Scoyk, Greg Poffenberger, Ivaylo Kirov, Lyubomir G. Nashev, Helong Zhao, Martin Martinov, Michael W. Deininger
Journal: Blood (2021)
Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer
Authors: Chenxue Mao, Juan Chen, Ting Zou, Yuankang Zhou, Junyan Liu, Xi Li, Xiangping Li, Min Li, Pinhua Pan, Wei Zhuo, Yang Gao, Shuo Hu, Desheng Xiao, Lin Wu, Zhan Wang, Heng Xu, Wen Yang, Yingjie Xu, Haihua Xiao, Kazuhiko Hanada, Wei Zhang, Honghao Zhou, Jiye Yin, Zhaoqian Liu
Journal: Acta Pharmaceutica Sinica B (2021)

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
Risk of Febrile Neutropenia in Very Elderly Patients Aged ≥80 Years Who Received R-CHOP Regimen: A Nationwide Analysis in Japan
Authors: Kensuke Matsuda, Taisuke Jo, Arika Nukina Shimura, Akira Honda, Yosuke Masamoto, Hideo Yasunaga, Mineo Kurokawa
Journal: Blood (2021)
Pharmacological Reduction of Mitochondrial Iron in AML Triggers a BAX/BAK Dependent Non-Canonical Cell Death Synergistic with Venetoclax
Authors: Sylvain Garciaz, Sebastian Müller, Andrew Guirguis, Fiona C. Brown, Yih-Chih Chan, Mathilde Poplineau, Kevin Tran, Kah-Lok Chan, Laura MacPherson, Brian Liddicoat, Enid Y. N. Lam, Tatiana Cañeque, Marian L. Burr, Veronique Litalien, Giovanna Pomilio, Estelle Duprez, David C.S. Huang, Sarah-Jane Dawson, Georg Ramm, Andrew G. Cox, Kristin K. Brown, Andrew H. Wei, Kate McArthur, Raphael Rodriguez, Mark A. Dawson
Journal: Blood (2021)
Abstract PO-046: The effect of neoadjuvant therapy on immune profiling of pancreatic ductal adenocarcinoma: A prospective study of the PREOPANC-1 randomized controlled trial
Authors: Diba Latifi, Willem de Koning, Sai ping Lau, Frederiek Grevers, Coen van Dam, Casper H. J. van Eijck, Dana A. M. Mustafa
Journal: Cancer Research (2021)

Abstract The randomized phase III trial (PREOPANC-1) that was performed in 16 centers in the Netherlands compared the effects of preoperative chemoradiotherapy (Gemcitabine and 2.4 Gy radiation) versus immediate surgery for resectable and borderline resectable pancreatic cancer. The outcomes of the secondary endpoints and predefined subgroup analyses suggest an advantage of the neoadjuvant approach. The aim of the present study was to investigate the changes in the immune microenvironment and infiltration caused by the neoadjuvant treatment. To that aim, we collected formalin-fixed, paraffin-embedded pancreatic cancer samples from all centers that participated in the PREOPANC -1 trial. We performed targeted gene expression using the PanCancer Immune Profiling panel of NanoString. Comparing 50 samples of the patient who were subjected to neoadjuvant treatment to 46 treatment-naïve samples showed a distinct genetic profile induced by the neoadjuvant therapy. More than 250 immune-related genes were significantly differentially expressed between the two groups of samples. The results indicate that neoadjuvant therapy resets the innate immune activation in the tissue samples. A significantly higher infiltration of CD14+, CD33+, CSF1R+, and CD163+, MRC1+ cells were found in samples of the neoadjuvant arm. In contrast, B cells and various subtypes of T cells like CD8+ and FOXP3+ showed a significant decrease in the same samples. Pathway analysis revealed that the neoadjuvant treatment stimulated the expression of genes related to the complement activation, chemotaxis, and wound repair, while genes related to lymphocyte activation and adaptive immune responses were dominant in the treatment-naïve arm. In conclusion, this is the first comprehensive study to describe the immune-molecular changes as a result of neoadjuvant therapy in a randomized clinical trial. The results reveal the enrichment of the myeloid compartment following neoadjuvant therapy which was significantly associated with a survival benefit for the patients. Studying the personalized effect of neoadjuvant therapy will guide choosing the appropriate combined therapy for pancreatic cancer. Citation Format: Diba Latifi, Willem de Koning, Sai ping Lau, Frederiek Grevers, Coen van Dam, Casper H. J. van Eijck, Dana A. M. Mustafa. The effect of neoadjuvant therapy on immune profiling of pancreatic ductal adenocarcinoma: A prospective study of the PREOPANC-1 randomized controlled trial [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-046.
Low Frequency of T Cell and Antibody Responses to Vaccination Against Sars-Cov-2 in Patients Post Allogeneic Stem Cell Transplantation in Comparison with Chronic Myeloid Malignancy Patients
Authors: Patrick Harrington, Katie Doores, Chandan Saha, Jamie Saunders, Deepti H. Radia, Shahram Kordasti, Richard Dillon, Kavita Raj, Jeffrey Seow, Carl Graham, Thomas Lechmere, Sukran Saglam, Fiona Child, Amy O'Reilly, Andreas Espehana, Varun Mehra, Donal P. McLornan, Michael Malim, Claire N. Harrison, Hugues de Lavallade
Journal: Blood (2021)
Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone: Update of the Phase 3 MAIA Trial
Authors: Aurore Perrot, Thierry Facon, Shaji Kumar, Torben Plesner, Robert Z. Orlowski, Philippe Moreau, Nizar J. Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael E. O'Dwyer, Chris P. Venner, Katja Weisel, Joseph R. Mace, Noopur S. Raje, Mourad Tiab, Magaret Macro, Laurent Frenzel, Xavier Leleu, Kevin Liu, John Fastenau, Katharine S. Gries, Kai Fai Ho, Pankaj Mistry, Brenda Tromp, Maria Delioukina, Jessica Vermeulen, Saad Z. Usmani
Journal: Blood (2021)
Single Cell Transcriptomic Profiling of Patient-Derived Xenografts of Mantle Cell Lymphoma Reveals a Special Tumor Cell Population: Seed Cells for Disease Dissemination and Progression
Authors: Vivian Changying Jiang, Qingsong Cai, Dapeng Hao, Yang Liu, Yijing Li, Yuxuan Che, Joseph McIntosh, Alexa A Jordan, Zhihong Chen, Angela Leeming, Lei Nie, Linghua Wang, Michael Wang
Journal: Blood (2021)
Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank
Authors: Susan L. Slager, Sameer A. Parikh, Sara J. Achenbach, Geffen Kleinstern, Nicholas J. Boddicker, Aaron D. Norman, Kari G. Rabe, Connie E. Lesnick, Timothy G. Call, Janet E. Olson, James R. Cerhan, Neil E. Kay, Celine M. Vachon, Esteban Braggio, Curtis A. Hanson, Tait Shanafelt
Journal: Blood (2021)
Noninvasive Cell-of-Origin Classification of Diffuse Large B-Cell Lymphoma Using Inferred Gene Expression from Cell-Free DNA Sequencing
Authors: Mohammad Shahrokh Esfahani, Stefan Alig, Mahya Mehrmohamadi, Emily G. Hamilton, Daniel A King, Andre Schultz, Chloe B. Steen, Charles Macaulay, Brian Sworder, David M. Kurtz, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2021)
A New Diagnostic Classification Tool for Pulmonary Chronic Graft-Versus-Host-Disease: Adaptation of the International Society for Heart and Lung Transplantation Chronic Lung Allograft Dysfunction Consensus Criteria
Authors: Yifan Pang, Ananth V. Charya, Michael B. Keller, Arlene Sirajuddin, Noa G. Holtzman, Sean Agbor-Enoh, Steven Z. Pavletic
Journal: Blood (2021)
Prospective Changes of Pancreatic Iron in Thalassemia Major
Authors: Alessia Pepe, Laura Pistoia, Crocetta Argento, Luciana Rigoli, Monica Benni, Cristina Paci, Piera Giovangrossi, Aurelio Maggio, Gennaro Restaino, Ada Riva, Vincenzo Positano, Antonella Meloni
Journal: Blood (2021)
High Throughput Single-Cell Simultaneous Genotyping and Chromatin Accessibility Reveals Genotype to Phenotype Relationship in Human Myeloproliferation
Authors: Robert M. Myers, Franco Izzo, Tamara Prieto, Eleni Mimitou, Ramya Raviram, Ronan Chaligne, Ronald Hoffman, Maximilian Stahl, Omar Abdel-Wahab, Bridget Marcellino, Peter Smibert, Dan A. Landau
Journal: Blood (2021)
A Multicenter, Prospective Study for Pediatric Chronic Myeloid Leukemia in Chronic Phase: The JPLSG CML-08 Study
Authors: Hiroyuki Shimada, Akihiro Watanabe, Masaki Ito, Chikako Tono, Haruko Shima, Yuki Yuza, Hideki Muramatsu, Masahiko Okada, Akihiko Tanizawa
Journal: Blood (2021)
Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation
Authors: Christian Rolfo, Noy Meshulami, Alessandro Russo, Florian Krammer, Adolfo García-Sastre, Philip C. Mack, Jorge E. Gomez, Nina Bhardwaj, Amin Benyounes, Rafael Sirera, Amy Moore, Nicholas Rohs, Claudia I. Henschke, David Yankelevitz, Jennifer King, Yu Shyr, Paul A. Bunn, John D. Minna, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2021)
Prognostic Impacts of Additional Cytogenetic Abnormalities Acquired at the First Relapse in Adult Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplant in Second Complete Remission
Authors: Hiroaki Shimizu, Junichi Mukae, Naoki Shingai, Takashi Toya, Yuho Najima, Takeshi Kobayashi, Nahoko Hatsumi, Satoru Takada, Hiroshi Handa, Kyoko Haraguchi, Yoshiki Okuyama, Hisashi Sakamaki, Kazuteru Ohashi, Noriko Doki
Journal: Blood (2021)
Major Findings of the Angioplasty Procedure in Cohort of the Patients: A Epidemiological/Observational Study
Authors: Rodrigo Bottura Nuevo Viveiros de Araújo, Wilson Pedro Guimarães Neto, Júlio Cesar Queiroz de França, Moacir Fernandes de Godoy, Márcio Antônio dos Santos, Flávio Corrêa Pivatelli, Márcio Rogério de Souza Braite
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Introduction: According to data from the World Health Organization of 2017, of the 21.7 million deaths from these diseases, more than ten million occur due to atherosclerotic coronary disease. Objective: Therefore, the present study aimed to analyze the main clinical data in terms of coronary angiography findings, as well as to know if the types of lesions found are related to acute myocardial infarction and whether gender and age predictors influence these events. Methods: A total of 502 participants (Female: n=174; Male: n=328) were submitted to eligibility analysis, followed by the rules STROBE. The present study followed a retrospective longitudinal with epidemiological/observational profile study on the analysis of the profile of patients who underwent angioplasty at Brazil. As there were continuous and categorical predictors and the response predictors, linear regression and was applied. For all linear regression tests, alpha level lower than 0.05 was adopted as significant. Results and Conclusion: According to the results in the evaluated cohort of the present study, it can be known that the presence of lesions above 50.0% in the LCT, P. Descendant, Circumflex, Right Coronary, Saphenous Bridge did not imply the occurrence of Stable, AMI – ST events. (NOT), AMI-ST and Complications, with a significant statistical difference, p &lt;0.05, not finding any relationship between them. Moreover, it was observed that the Gender and Age predictors statistically influenced the response of the P. Descendant, Circumflex, Right Coronary and Complications predictors, with p &lt;0.05.
Modulation of transforming growth factor-β-induced kidney fibrosis by leucine-rich ⍺-2 glycoprotein-1
Authors: Quan Hong, Hong Cai, Lu Zhang, Zhengzhe Li, Fang Zhong, Zhaohui Ni, Guangyan Cai, Xiang-Mei Chen, John Cijiang He, Kyung Lee
Journal: Kidney International (2021)
Abstract 9463: Effects of Surgical and FFP2 Masks on Cardiopulmonary Exercise Capacity in Patients With Heart Failure
Authors: Alexander Kogel, Pierre Hepp, Tina Stegmann, Adrienn Tuennemann-Tarr, Roberto Falz, Patrick Fischer, Felix Mahfoud, Ulrich Laufs, Sven Fikenzer
Journal: Circulation (2021)

Introduction: Surgical and FFP2 masks are recommended to reduce transmission of SARS-CoV-2. The cardiopulmonary effects of facemasks in patients with chronic heart failure are unknown. This prospective, cross-over study quantified the effects of wearing no mask (nm), surgical mask (sm), and FFP2 mask (ffpm) in 12 patients with clinically stable chronic heart failure (HF) (age 63.8±12 years, left ventricular ejection fraction (LVEF) 43.8±11 %, NTProBNP 573±567 pg/ml). Methods: The patients underwent spiroergometry with and without masks in a randomized sequence. Comfort/discomfort was assessed using a standardized questionnaire. Results: Maximum power was reduced with both types of masks (nm: 108.3 W vs. sm: 101.2 W vs. ffpm: 95.6 W, p&lt;0.01). Maximum respiratory oxygen uptake (1499ml/min vs. 1481 ml/min vs. 1300 ml/min, p=0.95 and &lt;0.01), peak ventilation (62.1 l/min vs. 56.4 l/min vs. 50.3 l/min, p=0.15 and p&lt;0.05) and O2-pulse (11.6 ml/beat vs. 11.8 ml/beat vs. 10.6 ml/beat, p=0.87 and p&lt;0.01) were significantly changed with ffpm but not sm. Discomfort was moderately but significantly increased (nm: 1.6 vs. sm: 3.4 vs. ffpm: 4.4, p&lt;0.05). Conclusion: Both surgical and FFP masks reduce exercise capacity in heart failure patients, while FFP2 masks reduce oxygen uptake and peak ventilation.
Clinical Features and Cytoreduction Therapy in Children with Newly Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis
Authors: Georgios E. Christakopoulos, Kendra N Walker, Lei Wang, Clifford Takemoto, Yan Zheng, Ching-Hon Pui, Raul C Ribeiro, Stanley B Pounds, Jeffrey E. Rubnitz, Hiroto Inaba
Journal: Blood (2021)
Tyrosine kinase inhibitor prodrug-loaded liposomes for controlled release at tumor microenvironment
Authors: Stefano Salmaso, Francesca Mastrotto, Marco Roverso, Valentina Gandin, Sara De Martin, Daniela Gabbia, Michele De Franco, Christian Vaccarin, Marco Verona, Adriana Chilin, Paolo Caliceti, Sara Bogialli, Giovanni Marzaro
Journal: Journal of Controlled Release (2021)
Abstract 13848: Assessment of Frailty in Patients With Advanced Heart Failure Before and After LVAD Implantation
Authors: Cassandra Heaney, Ravi K Vuthoori, Gregory Gibson, Edmund Miller, Harold Fernandez, Brian Lima, James Taylor, Kathleen Davidson, Kevin F Kennedy, David T Majure, Gerin R Stevens, Simon Maybaum
Journal: Circulation (2019)

Introduction: Assessment of frailty is essential for determining eligibility for advanced therapies (AT). Most programs use a subjective provider assessment (SPA) or “eye-ball” test. The Modified F...
Clozapine is my favorite color: Chemogenetic modulation of anxiety-related behavior in primates
Authors: Mark G. Baxter, Vincent D. Costa
Journal: Molecular Therapy (2021)

The development of technologies to reversibly manipulate neural circuitry has given rise to the prospect of more precisely targeted therapies to normalize brain function in neuropsychiatric disorders. These approaches must be feasible using viral vector-mediated gene transfer to be practical in primates. Chemogenetic tools have great potential in fulfilling this goal. Chemogenetic neuromodulation changes neuronal activity via a systemically administered drug that triggers artificial receptors placed in anatomically defined neuronal populations via viral vectors. 1 Roth B.L. DREADDs for Neuroscientists. Neuron. 2016; 89: 683-694 Abstract Full Text Full Text PDF PubMed Scopus (693) Google Scholar Roseboom et al. 2 Roseboom P.H. Mueller S.A.L. Oler J.A. Fox A.S. Riedel M.K. Elam V.R. Olsen M.E. Gomez J.L. Boehm M.A. DiFilippo A.H. et al. Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders. Mol. Ther. 2021; Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar show that inhibitory chemogenetic receptors expressed in the dorsal region of the amygdala of rhesus monkeys affects behavior in the human intruder paradigm, a model of anxious temperament in humans. In the human intruder paradigm, the monkey's behavior is observed while an unfamiliar human stands first in profile to the monkey, and then stares at the monkey, producing a mild social stressor (Figure 1). Inhibition of neurons in the dorsal region of the amygdala reduced freezing behavior in the human intruder paradigm compared with testing without chemogenetic inhibition, suggesting a reduction in the anxiety-like phenotype. This represents a step toward using chemogenetic strategies to modulate amygdala activity in neuropsychiatric disorders in humans. It may be especially effective in anxiety disorders, where there is converging evidence in humans and non-human primates that amygdala hyperactivity is a prominent feature. 3 Pagliaccio D. Pine D.S. Leibenluft E. Dal Monte O. Averbeck B.B. Costa V.D. Cross-species convergence in pupillary response: understanding human anxiety via non-human primate amygdala lesion. Soc. Cogn. Affect. Neurosci. 2019; 14: 591-599 Crossref PubMed Scopus (3) Google Scholar Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disordersRoseboom et al.Molecular TherapyApril 22, 2021In BriefUsing their nonhuman primate model of pathological anxiety, Roseboom, Mueller, and colleagues used viral vector/chemogenetic methods to reversibly inhibit amygdala activity and anxiety. This work in primates highlights a method and a brain target that could guide the development of chemogenetic strategies for the treatment of human neuropsychiatric disorders. Full-Text PDF
Abstract 12760: Association of Machine Learning-Derived Measures of Body Fat Distribution in >40,000 Individuals With Cardiometabolic Diseases
Authors: Saaket Agrawal, Marcus D Klarqvist, Nathaniel Diamant, Patrick T Ellinor, Nehal N Mehta, Anthony Philippakis, Kenney Ng, Puneet Batra, Amit V Khera
Journal: Circulation (2021)

Background: Obesity is defined based on body-mass index (BMI), a proxy for overall adiposity. However, for any given BMI, individuals vary substantially in fat distribution. The clinical implicatio...