tbuckley/cabot-search huggingface dataset:
Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational study
Authors: Estrella Morenas-Rodríguez, Yan Li, Brigitte Nuscher, Nicolai Franzmeier, Chengjie Xiong, Marc Suárez-Calvet, Anne M Fagan, Stephanie Schultz, Brian A Gordon, Tammie L S Benzinger, Jason Hassenstab, Eric McDade, Regina Feederle, Celeste M Karch, Kai Schlepckow, John C Morris, Gernot Kleinberger, Bengt Nellgard, Jonathan Vöglein, Kaj Blennow, Henrik Zetterberg, Michael Ewers, Mathias Jucker, Johannes Levin, Randall J Bateman, Christian Haass, Sarah Adams, Ricardo Allegri, Aki Araki, Nicolas Barthelemy, Jacob Bechara, Sarah Berman, Courtney Bodge, Susan Brandon, William (Bill) Brooks, Jared Brosch, Jill Buck, Virginia Buckles, Kathleen Carter, Lisa Cash, Charlie Chen, Jasmeer Chhatwal, Patricio Chrem, Jasmin Chua, Helena Chui, Carlos Cruchaga, Gregory S Day, Chrismary De La Cruz, Darcy Denner, Anna Diffenbacher, Aylin Dincer, Tamara Donahue, Jane Douglas, Duc Duong, Noelia Egido, Bianca Esposito, Marty Farlow, Becca Feldman, Colleen Fitzpatrick, Shaney Flores, Nick Fox, Erin Franklin, Nelly Friedrichsen, Hisako Fujii, Samantha Gardener, Bernardino Ghetti, Alison Goate, Sarah Goldberg, Jill Goldman, Alyssa Gonzalez, Susanne Gräber-Sultan, Neill Graff-Radford, Morgan Graham, Julia Gray, Emily Gremminger, Miguel Grilo, Alex Groves, Lisa Häsler, Cortaiga Hellm, Elizabeth Herries, Laura Hoechst-Swisher, Anna Hofmann, David Holtzman, Russ Hornbeck, Yakushev Igor, Ryoko Ihara, Takeshi Ikeuchi, Snezana Ikonomovic, Kenji Ishii, Clifford Jack, Gina Jerome, Erik Johnson, Stephan Käser, Kensaku Kasuga, Sarah Keefe, William (Bill) Klunk, Robert Koeppe, Deb Koudelis, Elke Kuder-Buletta, Christoph Laske, Allan Levey, Oscar Lopez, Jacob Marsh, Rita Martinez, Ralph Martins, Neal Scott Mason, Colin Masters, Kwasi Mawuenyega, Austin McCullough, Arlene Mejia, James MountzMD, Cath Mummery, Neelesh Nadkarni, Akemi Nagamatsu, Katie Neimeyer, Yoshiki Niimi, James Noble, Joanne Norton, Brigitte Nuscher, Antoinette O'Connor, Ulricke Obermüller, Riddhi Patira, Richard Perrin, Lingyan Ping, Oliver Preische, Alan Renton, John Ringman, Stephen Salloway, Peter Schofield, Michio Senda, Nick Seyfried, Kristine Shady, Hiroyuki Shimada, Wendy Sigurdson, Jennifer Smith, Lori Smith, Beth Snitz, Hamid Sohrabi, Sochenda Stephens, Kevin Taddei, Sarah Thompson, Peter Wang, Qing Wang, Elise Weamer, Jinbin Xu, Xiong Xu
Journal: The Lancet Neurology (2022)

Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease.
Targeting mutations in cancer
Authors: Michael R. Waarts, Aaron J. Stonestrom, Young C. Park, Ross L. Levine
Journal: Journal of Clinical Investigation (2022)

Targeted therapies have come to play an increasingly important role in cancer therapy over the past two decades. This success has been made possible in large part by technological advances in sequencing, which have greatly advanced our understanding of the mutational landscape of human cancer and the genetic drivers present in individual tumors. We are rapidly discovering a growing number of mutations that occur in targetable pathways, and thus tumor genetic testing has become an important component in the choice of appropriate therapies. Targeted therapy has dramatically transformed treatment outcomes and disease prognosis in some settings, whereas in other oncologic contexts, targeted approaches have yet to demonstrate considerable clinical efficacy. In this Review, we summarize the current knowledge of targetable mutations that occur in a range of cancers, including hematologic malignancies and solid tumors such as non-small cell lung cancer and breast cancer. We outline seminal examples of druggable mutations and targeting modalities and address the clinical and research challenges that must be overcome to maximize therapeutic benefit.
DNA
Authors: Emily Franklin
Journal: JAMA (2022)

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
Corrigendum to “Apical sodium-dependent bile acid transporter, drug target for bile acid related diseases and delivery target for prodrugs: Current and future challenges” [Pharmacology &amp; Therapeutics 212 (2020) 107539]
Authors: Ming Li, Qian Wang, Yong Li, Shengtian Cao, Yingjun Zhang, Zhongqing Wang, Guozhu Liu, Jing Li, Baohua Gu
Journal: Pharmacology & Therapeutics (2022)
Radiographic Evolution of Presumed Septic Pulmonary Emboli
Authors: Zarah Haleem, Jeremy D. Gradon
Journal: New England Journal of Medicine (2022)

A 41-year-old woman with a history of opioid use disorder presented with shortness of breath, chest pain, and fever. A chest radiograph showed peripheral, nodular airspace opacities. The patient left the hospital but later returned with worsening symptoms, and chest radiographic findings were suggestive of septic pulmonary emboli.
IL-17A–producing γδT cells promote muscle regeneration in a microbiota-dependent manner
Authors: Alexander O. Mann, Bola S. Hanna, Andrés R. Muñoz-Rojas, Inga Sandrock, Immo Prinz, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (2022)

Subsequent to acute injury, skeletal muscle undergoes a stereotypic regenerative process that reestablishes homeostasis. Various types of innate and adaptive immunocytes exert positive or negative influences at specific stages along the course of muscle regeneration. We describe an unanticipated role for γδT cells in promoting healthy tissue recovery after injection of cardiotoxin into murine hindlimb muscle. Within a few days of injury, IL-17A-producing γδT cells displaying primarily Vγ6+ antigen receptors accumulated at the wound site. Punctual ablation experiments showed that these cells boosted early inflammatory events, notably recruitment of neutrophils; fostered the proliferation of muscle stem and progenitor cells; and thereby promoted tissue regeneration. Supplementation of mice harboring low numbers of IL-17A+ γδT cells with recombinant IL-17A largely reversed their inflammatory and reparative defects. Unexpectedly, the accumulation and influences of γδT cells in this experimental context were microbiota dependent, unveiling an orthogonal perspective on the treatment of skeletal muscle pathologies such as catastrophic wounds, wasting, muscular dystrophies, and myositides.
Antibiotic use from formal and informal healthcare providers in the Democratic Republic of Congo: a population-based study in two health zones
Authors: Brecht Ingelbeen, Delphin M. Phanzu, Marie-France Phoba, Mi Y.N. Budiongo, Neamin M. Berhe, Frédéric K. Kamba, Lisette Kalonji, Bijou Mbangi, Liselotte Hardy, Bieke Tack, Justin Im, Leonardo W. Heyerdahl, Raquel Inocencio Da Luz, Marc J.M. Bonten, Octavie Lunguya, Jan Jacobs, Placide Mbala, Marianne A.B. van der Sande
Journal: Clinical Microbiology and Infection (2022)

In the Democratic Republic of Congo and other low-resource countries, community-acquired pathogens are increasingly resistant to most locally available antibiotics. To guide efforts to optimize antibiotic use to limit antibiotic resistance, we quantified healthcare provider-specific and community-wide antibiotic use.From household surveys, we estimated monthly healthcare visit rates by provider. From healthcare visit exit surveys, we estimated prevalence, defined daily doses, and access/watch/reserve distribution of antibiotic use by provider. Combining both, we estimated community-wide antibiotic use rates.Of 88.7 (95% CI 81.9-95.4) healthcare visits per 1000 person-months (n = 31221), visits to private clinics (31.0, 95% CI 30.0-32.0) and primary health centres (25.5, 95% CI 24.6-26.4) were most frequent. Antibiotics were used during 64.3% (95% CI 55.2-73.5%, 162/224) of visits to private clinics, 51.1% (95% CI 45.1-57.2%, 245/469) to health centres, and 48.8% (95% CI 44.4-53.2%, 344/454) to medicine stores. Antibiotic defined daily doses per 1000 inhabitants per day varied between 1.75 (95% CI 1.02-2.39) in rural Kimpese and 10.2 (95% CI 6.00-15.4) in (peri) urban Kisantu, mostly explained by differences in healthcare utilisation (respectively 27.8 versus 105 visits per 1000 person-months), in particular of private clinics (1.23 versus 38.6 visits) where antibiotic use is more frequent. The fraction of Watch antibiotics was 30.3% (95% CI 24.6-35.9%) in private clinics, 25.6% (95% CI 20.2-31.1%) in medicine stores, and 25.1% (95% CI 19.0-31.2%) in health centres. Treatment durations <3 days were more frequent at private clinics (5.3%, 9/169) and medicine stores (4.1%, 14/338) than at primary health centres (1.8%, 5/277).Private healthcare providers, ubiquitous in peri-urban settings, contributed most to community-wide antibiotic use and more frequently dispensed Watch antibiotics and shortened antibiotic courses. Efforts to optimize antibiotic use should include private providers at community level.
Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C
Authors: Ming Zhao, Kaiqun Ren, Xiwen Xiong, Yue Xin, Yujie Zou, Jason C. Maynard, Angela Kim, Alexander P. Battist, Navya Koneripalli, Yusu Wang, Qianyue Chen, Ruyue Xin, Chenyan Yang, Rong Huang, Jiahui Yu, Zan Huang, Zengdi Zhang, Haiguang Wang, Daoyuan Wang, Yihui Xiao, Oscar C. Salgado, Nicholas N. Jarjour, Kristin A. Hogquist, Xavier S. Revelo, Alma L. Burlingame, Xiang Gao, Jakob von Moltke, Zhaoyu Lin, Hai-Bin Ruan
Journal: Immunity (2022)
miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease
Authors: Carlos Perez-Sanchez, Ariana Barbera Betancourt, Paul A. Lyons, Zinan Zhang, Chenqu Suo, James C. Lee, Eoin F. McKinney, Louise K. Modis, Christian Ellson, Kenneth G.C. Smith
Journal: The Journal of Experimental Medicine (2022)

MicroRNAs are critical regulators of gene expression controlling cellular processes including inflammation. We explored their role in the pathogenesis of inflammatory bowel disease (IBD) and identified reduced expression of miR-374a-5p in IBD monocytes that correlated with a module of up-regulated genes related to the inflammatory response. Key proinflammatory module genes, including for example TNFα, IL1A, IL6, and OSM, were inversely correlated with miR-374a-5p and were validated in vitro. In colonic biopsies, miR-374a-5p was again reduced in expression and inversely correlated with the same inflammatory module, and its levels predicted subsequent response to anti-TNF therapy. Increased miR-374a-5p expression was shown to control macrophage-driven inflammation by suppressing proinflammatory mediators and to reduce the capacity of monocytes to migrate and activate T cells. Our findings suggest that miR-374a-5p reduction is a central driver of inflammation in IBD, and its therapeutic supplementation could reduce monocyte-driven inflammation in IBD or other immune-mediated diseases.
Novel phthalimides regulating PD-1/PD-L1 interaction as potential immunotherapy agents
Authors: Chengliang Sun, Yao Cheng, Xiaojia Liu, Gefei Wang, Wenjian Min, Xiao Wang, Kai Yuan, Yi Hou, Jiaxing Li, Haolin Zhang, Haojie Dong, Liping Wang, Chenguang Lou, Yanze Sun, Xinmiao Yu, Hongbin Deng, Yibei Xiao, Peng Yang
Journal: Acta Pharmaceutica Sinica B (2022)

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1) have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy. Despite the inherent advantages of small-molecule inhibitors over antibodies, the discovery of small-molecule inhibitors has fallen behind that of antibody drugs. Based on docking studies between small molecule inhibitor and PD-L1 protein, changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein, which was not reported before. A series of novel phthalimide derivatives from structure-based rational design was synthesized. P39 was identified as the best inhibitor with promising activity, which not only inhibited PD-1/PD-L1 interaction (IC50 = 8.9 nmol/L), but also enhanced killing efficacy of immune cells on cancer cells. Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins, thereby blocking the binding of PD-1/PD-L1. Moreover, P39 exhibited a favorable safety profile with a LD50 > 5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8+ T cell activation. All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.
Editor's Note: Nkx2–8 Downregulation Promotes Angiogenesis and Activates NF-κB in Esophageal Cancer
Authors: Chuyong Lin, Libing Song, Hui Gong, Aibin Liu, Xi Lin, Jueheng Wu, Mengfeng Li, Jun Li
Journal: Cancer Research (2022)

The editors are publishing this note to alert readers to a concern about this article (1). The editors were made aware of duplications in Fig. 3A and B. Specifically, in Fig. 3A, the authors used the incorrect image for the ESCC Kyse510/Nkx2–8 RNAi#1 group, which was duplicated from Fig. 8A in ref. 2. In Fig. 3B, regions from the same image were used in the Kyse510/Vector, Kyse30/Scrambled vector, and Kyse510/Scrambled vector groups. Also in Fig. 3B, regions from the same image were used in the Kyse30/Nkx2–8-RNAi#2 and Kyse510/Nkx2–8-RNAi#2 groups. Because satisfactorily corrected figures could not be provided, the editors are publishing this note to alert readers to these concerns.
Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study
Authors: Valérie Cochen De Cock, Pauline Dodet, Smaranda Leu-Semenescu, Cécile Aerts, Giovanni Castelnovo, Beatriz Abril, Sophie Drapier, Hélène Olivet, Anne-Gaëlle Corbillé, Laurène Leclair-Visonneau, Magali Sallansonnet-Froment, Marie Lebouteux, Mathieu Anheim, Elisabeth Ruppert, Nicolas Vitello, Alexandre Eusebio, Isabelle Lambert, Ana Marques, Maria Livia Fantini, David Devos, Christelle Monaca, Nicolas Benard-Serre, Sandy Lacombe, Marie Vidailhet, Isabelle Arnulf, Mohamed Doulazmi, Emmanuel Roze
Journal: The Lancet Neurology (2022)
Targeted immunomodulation therapy for cardiac repair by platelet membrane engineering extracellular vesicles via hitching peripheral monocytes
Authors: Qiyu Li, Zheyong Huang, Qiaozi Wang, Jinfeng Gao, Jing Chen, Haipeng Tan, Su Li, Zhengmin Wang, Xueyi Weng, Hongbo Yang, Zhiqing Pang, Yanan Song, Juying Qian, Junbo Ge
Journal: Biomaterials (2022)
Uncoupling immune trajectories of response and adverse events from anti-PD-1 immunotherapy in hepatocellular carcinoma
Authors: Samuel Chuah, Joycelyn Lee, Yuan Song, Hyung-Don Kim, Martin Wasser, Neslihan A. Kaya, Kyunghye Bang, Yong Joon Lee, Seung Hyuck Jeon, Sheena Suthen, Shamirah A’Azman, Gerald Gien, Chun Jye Lim, Camillus Chua, Sharifah Nur Hazirah, Hong Kai Lee, Jia Qi Lim, Tony K.H. Lim, Joe Yeong, Jinmiao Chen, Eui-Cheol Shin, Salvatore Albani, Weiwei Zhai, Changhoon Yoo, Haiyan Liu, Su Pin Choo, David Tai, Valerie Chew
Journal: Journal of Hepatology (2022)

While immune checkpoint blockade (ICB) has shown promise in patients with hepatocellular carcinoma (HCC), it is associated with modest response rates and immune-related adverse events (irAEs) are common. In this study, we aimed to decipher immune trajectories and mechanisms of response and/or irAEs in patients with HCC receiving anti-programmed cell death 1 (anti-PD-1) therapy.Pre- and on-treatment peripheral blood samples (n = 60) obtained from 32 patients with HCC (Singapore cohort) were analysed by cytometry by time-of-flight and single-cell RNA sequencing, with flow cytometric validation in an independent Korean cohort (n = 29). Mechanistic validation was conducted by bulk RNA sequencing of 20 pre- and on-treatment tumour biopsies and using a murine HCC model treated with different immunotherapeutic combinations.Single-cell analyses identified CXCR3+CD8+ effector memory T (TEM) cells and CD11c+ antigen-presenting cells (APC) as associated with response (p = 0.0004 and 0.0255, respectively), progression-free survival (p = 0.00079 and 0.0015, respectively), and irAEs (p = 0.0034 and 0.0125, respectively) in anti-PD-1-treated patients with HCC. Type-1 conventional dendritic cells were identified as the specific APC associated with response, while 2 immunosuppressive CD14+ myeloid clusters were linked to reduced irAEs. Further analyses of CXCR3+CD8+ TEM cells showed cell-cell interactions specific to response vs. irAEs, from which the anti-PD-1 and anti-TNFR2 combination was harnessed to uncouple these effects, resulting in enhanced response without increased irAEs in a murine HCC model.This study identifies early predictors of clinical response to anti-PD-1 ICB in patients with HCC and offers mechanistic insights into the immune trajectories of these immune subsets at the interface between response and toxicity. We also propose a new combination immunotherapy for HCC to enhance response without exacerbating irAEs.NCT03695952.Response rates to immune checkpoint blockade (ICB) treatment in hepatocellular carcinoma (HCC) remain modest and adverse events are common. Herein, we identified early predictors of response and gained an in-depth understanding of the immunological mechanisms behind response and adverse events in patients with HCC treated with ICB. We also proposed a new combination immunotherapy for HCC that enhances response without exacerbating adverse events.
Race and Urinary Tract Infections in Young Children With Fever
Authors: Olakunle B. Akintemi, Kenneth B. Roberts
Journal: JAMA Pediatrics (2022)

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 Pediatrics 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 Pediatrics journal
A Frequently Missed Pulmonary Infarction
Authors: Yu Ji, Yaru Wang, Chunchun Shao, Yong Cui, Na Su, Guangrui Shao, Jingsong Zheng
Journal: Clinical Nuclear Medicine (2022)

Purpose This study aimed to summarize the clinical and 18 F-FDG PET/CT manifestations of hilar tumor–induced pulmonary infarction. Methods A retrospective analysis was performed on patients with hilar masses who underwent FDG PET/CT scans between July 2015 and January 2021 and had complete clinical data. Pulmonary infarction was confirmed by concurrent chest CT and imaging follow-up or pathology. Results A total of 58 patients (mean age, 56 [SD, 13] years; 44 males) with 122 infarcts were included in the study. Hilar masses were mostly associated with small cell lung cancer (64%). The most common clinical manifestations were cough (64%) and hemoptysis (36%). Most patients (62%) had multiple pulmonary infarcts. The CT findings of pulmonary infarcts included the “Hampton hump” (48%) and patchy consolidation (52%). The density of infarcts included “bubbly consolidation” (61%) and “homogenous consolidation” (39%). The metabolic activity of 95 infarcts (78%) was higher than lung parenchyma, with the SUV max of 3.3 (SD, 1.1). The metabolic patterns on PET/CT were “rim sign,” “mismatch between PET and CT,” and “no metabolism.” Pulmonary vein involvement was found in 25 patients (43%), pleural effusion in 22 patients (38%), and the pleural curvilinear sign in 8 patients (14%). Conclusions The clinical manifestations of hilar tumor–induced pulmonary infarction are not specific, and 18 F-FDG PET/CT could be an effective diagnostic tool.