tbuckley/cabot-search huggingface dataset:
Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level
Authors: Yingcheng Wu, Shuaixi Yang, Jiaqiang Ma, Zechuan Chen, Guohe Song, Dongning Rao, Yifei Cheng, Siyuan Huang, Yifei Liu, Shan Jiang, Jinxia Liu, Xiaowu Huang, Xiaoying Wang, Shuangjian Qiu, Jianmin Xu, Ruibin Xi, Fan Bai, Jian Zhou, Jia Fan, Xiaoming Zhang, Qiang Gao
Journal: Cancer Discovery (2021)

Abstract Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell RNA sequencing and spatial transcriptomics. Strikingly, the metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as MRC1+ CCL18+ M2-like macrophages. We further developed scMetabolism, a computational pipeline for quantifying single-cell metabolism, and observed that those macrophages harbored enhanced metabolic activity. Interestingly, neoadjuvant chemotherapy could block this status and restore the antitumor immune balance in responsive patients, whereas the nonresponsive patients deteriorated into a more suppressive one. Our work described the immune evolution of metastasis and uncovered the black box of how tumors respond to neoadjuvant chemotherapy. Significance: We present a single-cell and spatial atlas of colorectal liver metastasis and found the highly metabolically activated MRC1+ CCL18+ M2-like macrophages in metastatic sites. Efficient neoadjuvant chemotherapy can slow down such metabolic activation, raising the possibility to target metabolism pathways in metastasis. This article is highlighted in the In This Issue feature, p. 1
Live Birth with or without Preimplantation Genetic Testing for Aneuploidy
Authors: Junhao Yan, Yingying Qin, Han Zhao, Yun Sun, Fei Gong, Rong Li, Xiaoxi Sun, Xiufeng Ling, Hong Li, Cuifang Hao, Jichun Tan, Jing Yang, Yimin Zhu, Fenghua Liu, Dawei Chen, Daimin Wei, Juanjuan Lu, Tianxiang Ni, Wei Zhou, Keliang Wu, Yuan Gao, Yuhua Shi, Yao Lu, Ting Zhang, Wei Wu, Xiang Ma, Hailan Ma, Jing Fu, Junqiang Zhang, Qingxia Meng, Heping Zhang, Richard S. Legro, Zi-Jiang Chen
Journal: New England Journal of Medicine (2021)

Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).
TCTAP A-078 A Non-randomized, Clinical Registry of the DynamX Novolimus Eluting Coronary Bioadaptor System in the Treatment of Patients With De Novo Native Coronary Artery Lesions - “DynamX Hong Kong Registry”
Authors: Bryan Ping-Yen Yan, Li Wah Tam, Sunny C.F. Tsang, Wai Kin Chi, Frankie CC. Tam, Michael Kang-Yin Lee
Journal: Journal of the American College of Cardiology (2022)
Disparities in Air Pollution Exposure in the United States by Race/Ethnicity and Income, 1990–2010
Authors: Jiawen Liu, Lara P. Clark, Matthew J. Bechle, Anjum Hajat, Sun-Young Kim, Allen L. Robinson, Lianne Sheppard, Adam A. Szpiro, Julian D. Marshall
Journal: Environmental Health Perspectives (2021)

Background: Few studies have investigated air pollution exposure disparities by race/ethnicity and income across criteria air pollutants, locations, or time. Objective: The objective of this study was to quantify exposure disparities by race/ethnicity and income throughout the contiguous United States for six criteria air pollutants, during the period 1990 to 2010. Methods: We quantified exposure disparities among racial/ethnic groups (non-Hispanic White, non-Hispanic Black, Hispanic (any race), non-Hispanic Asian) and by income for multiple spatial units (contiguous United States, states, urban vs. rural areas) and years (1990, 2000, 2010) for carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matter with aerodynamic diameter ≤2.5μm (PM2.5; excluding year-1990), particulate matter with aerodynamic diameter ≤10μm (PM10), and sulfur dioxide (SO2). We used census data for demographic information and a national empirical model for ambient air pollution levels. Results: For all years and pollutants, the racial/ethnic group with the highest national average exposure was a racial/ethnic minority group. In 2010, the disparity between the racial/ethnic group with the highest vs. lowest national-average exposure was largest for NO2 [54% (4.6 ppb)], smallest for O3 [3.6% (1.6 ppb)], and intermediate for the remaining pollutants (13%–19%). The disparities varied by U.S. state; for example, for PM2.5 in 2010, exposures were at least 5% higher than average in 63% of states for non-Hispanic Black populations; in 33% and 26% of states for Hispanic and for non-Hispanic Asian populations, respectively; and in no states for non-Hispanic White populations. Absolute exposure disparities were larger among racial/ethnic groups than among income categories (range among pollutants: between 1.1 and 21 times larger). Over the period studied, national absolute racial/ethnic exposure disparities declined by between 35% (0.66μg/m3; PM2.5) and 88% (0.35 ppm; CO); relative disparities declined to between 0.99× (PM2.5; i.e., nearly zero change) and 0.71× (CO; i.e., a ∼29% reduction). Discussion: As air pollution concentrations declined during the period 1990 to 2010, absolute (and to a lesser extent, relative) racial/ethnic exposure disparities also declined. However, in 2010, racial/ethnic exposure disparities remained across income levels, in urban and rural areas, and in all states, for multiple pollutants. https://doi.org/10.1289/EHP8584
Amisulpride and olanzapine combination treatment versus each monotherapy in acutely ill patients with schizophrenia in Germany (COMBINE): a double-blind randomised controlled trial
Authors: Christian Schmidt-Kraepelin, Sandra Feyerabend, Christina Engelke, Mathias Riesbeck, Eva Meisenzahl-Lechner, Pablo-Emilio Verde, Christoph U Correll, Michael Kluge, Christian Makiol, Andrea Neff, Christina Lange, Susanne Englisch, Mathias Zink, Berthold Langguth, Timm B Poeppl, Dirk Reske, Euphrosyne Gouzoulis-Mayfrank, Gerhard Gründer, Alkomiet Hasan, Anke Brockhaus-Dumke, Markus Jäger, Jessica Baumgärtner, Stefan Leucht, Joachim Cordes, Christian Schmidt-Kraepelin, Joachim Cordes, Sandra Feyerabend, Christina Engelke, Mathias Riesbeck, Eva Meisenzahl-Lechner, Wolfgang Gaebel, Martina Deiß, Natalia Sofie, Viktoria Galuba, Frank Wiechmann, Birgit Janssen, Michael Kluge, Christian Makiol, Lisa Kertzscher, Andrea Neff, Christina Lange, Susanne Englisch, Mathias Zink, Anna Becker, Sandra Muszinski, Gerhard Gründer, Berthold Langguth, Timm Poeppl, Elmar Frank, Peter Kreuzer, Dirk Reske, Euphrosyne Gouzoulis-Mayfrank, Tanja Veselinovic, Alkomiet Hasan, Peter Falkai, Elias Wagner, Anke Brockhaus-Dumke, Bettina Klos, Markus Jäger, Fabian Lang, Paulo Kling-Lourenço, Jessica Baumgärtner, Alkomiet Hasan, Nadine Dreimüller, Christoph Hiemke, Stefan Leucht, Stephan Heres, Claudia Leucht, Hans-Jörg Assion, Bernhard Kis, David Zilles-Wegner, Kai Kahl, Christoph Correll, Pablo-Emilio Verde, Henrike Kolbe, Anika Rottmann
Journal: The Lancet Psychiatry (2022)
Author's correction for Euro Surveill. 2021;26(44)
Journal: Eurosurveillance (2022)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Comparative sensitivity evaluation for 122 CE-marked rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021
RSPO2 and RANKL signal through LGR4 to regulate osteoclastic premetastatic niche formation and bone metastasis
Authors: Zhiying Yue, Xin Niu, Zengjin Yuan, Qin Qin, Wenhao Jiang, Liang He, Jingduo Gao, Yi Ding, Yanxi Liu, Ziwei Xu, Zhenxi Li, Zhengfeng Yang, Rong Li, Xiwen Xue, Yankun Gao, Fei Yue, Xiang H.-F. Zhang, Guohong Hu, Yi Wang, Yi Li, Geng Chen, Stefan Siwko, Alison Gartland, Ning Wang, Jianru Xiao, Mingyao Liu, Jian Luo
Journal: Journal of Clinical Investigation (2021)

Therapeutics targeting osteoclasts are commonly used treatments for bone metastasis; however, whether and how osteoclasts regulate premetastatic niche and bone tropism are largely unknown. In this study, we report that osteoclast precursors (OPs) can function as a premetastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interaction with their receptor LGR4, promoted osteoclastic premetastatic niche formation and enhanced BCa bone metastasis. This was achieved by RSPO2/RANKL-LGR4 signal modulating the WNT inhibitor DKK1 through Gαq and β-catenin signaling. DKK1 directly facilitated OP recruitment through suppression of its receptor LDL receptor–related protein 5 (LRP5) but not LRP6, upregulating Rnasek expression via inhibition of canonical WNT signaling. In clinical samples, RSPO2, LGR4, and DKK1 expression showed a positive correlation with BCa bone metastasis. Furthermore, soluble LGR4 extracellular domain (ECD) protein, acting as a decoy receptor for RSPO2 and RANKL, significantly alleviated bone metastasis and osteolytic lesions in a mouse bone metastasis model. These findings provide unique insights into the functional role of OPs as key components of the premetastatic niche for BCa bone metastasis and identify RSPO2/RANKL-LGR4 signaling as a promising target for inhibiting BCa bone metastasis.
High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma
Authors: Raphael Koch, Hans Gelderblom, Lianne Haveman, Benedicte Brichard, Heribert Jürgens, Sona Cyprova, Henk van den Berg, Wolf Hassenpflug, Anna Raciborska, Torben Ek, Daniel Baumhoer, Gerlinde Egerer, Hans Theodor Eich, Marleen Renard, Peter Hauser, Stefan Burdach, Judith Bovee, Fiona Bonar, Peter Reichardt, Jarmila Kruseova, Jendrik Hardes, Thomas Kühne, Torsten Kessler, Stephane Collaud, Marie Bernkopf, Trude Butterfaß-Bahloul, Catharina Dhooge, Sebastian Bauer, János Kiss, Michael Paulussen, Angela Hong, Andreas Ranft, Beate Timmermann, Jelena Rascon, Volker Vieth, Jukka Kanerva, Andreas Faldum, Markus Metzler, Wolfgang Hartmann, Lars Hjorth, Vivek Bhadri, Uta Dirksen
Journal: Journal of Clinical Oncology (2022)

Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion of autologous hematopoietic stem cells on event-free survival (EFS) and overall survival in high-risk Ewing sarcoma (EWS).Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding patients with only pulmonary metastases. Patients received six cycles of vincristine, ifosfamide, doxorubicin, and etoposide induction and eight cycles of vincristine, actinomycin D, and cyclophosphamide consolidation therapy. Patients were randomly assigned to receive additional TreoMel-HDT or no further treatment (control). The random assignment was stratified by number of bone metastases (1, 2-5, and > 5). The one-sided adaptive-inverse-normal-4-stage-design was changed after the first interim analysis via Müller-Schäfer method.Between 2009 and 2018, 109 patients were randomly assigned, and 55 received TreoMel-HDT. With a median follow-up of 3.3 years, there was no significant difference in EFS between TreoMel-HDT and control in the adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 to 1.32, intention-to-treat). Three-year EFS was 20.9% (95% CI, 11.5 to 37.9) in TreoMel-HDT and 19.2% (95% CI, 10.8 to 34.4) in control patients. The results were similar in the per-protocol collective. Males treated with TreoMel-HDT had better EFS compared with controls: median 1.0 years (95% CI, 0.8 to 2.2) versus 0.6 years (95% CI, 0.5 to 0.9); P = .035; HR 0.52 (0.28 to 0.97). Patients age < 14 years benefited from TreoMel-HDT with a 3-years EFS of 39.3% (95% CI, 20.4 to 75.8%) versus 9% (95% CI, 2.4 to 34); P = .016; HR 0.40 (0.19 to 0.87). These effects were similar in the per-protocol collective. This observation is supported by comparable results from the nonrandomized trial EE99R3.In patients with very high-risk EWS, additional TreoMel-HDT was of no benefit for the entire cohort of patients. TreoMel-HDT may be of benefit for children age < 14 years.
Workplace contact patterns in England during the COVID-19 pandemic: Analysis of the Virus Watch prospective cohort study
Authors: Sarah Beale, Susan Hoskins, Thomas Byrne, Wing Lam Erica Fong, Ellen Fragaszy, Cyril Geismar, Jana Kovar, Annalan M.D. Navaratnam, Vincent Nguyen, Parth Patel, Alexei Yavlinsky, Anne M. Johnson, Martie Van Tongeren, Robert W. Aldridge, Andrew Hayward
Journal: The Lancet Regional Health - Europe (2022)

Workplaces are an important potential source of SARS-CoV-2 exposure; however, investigation into workplace contact patterns is lacking. This study aimed to investigate how workplace attendance and features of contact varied between occupations across the COVID-19 pandemic in England.
Association of AXL and PD-L1 Expression with Clinical Outcomes in Patients with Advanced Renal Cell Carcinoma Treated with PD-1 Blockade
Authors: Stéphane Terry, Cécile Dalban, Nathalie Rioux-Leclercq, Julien Adam, Maxime Meylan, Stéphanie Buart, Antoine Bougoüin, Alexandra Lespagnol, Frédéric Dugay, Irelka Colina Moreno, Guillaume Lacroix, James B. Lorens, Gro Gausdal, Wolf H. Fridman, Fathia Mami-Chouaib, Nathalie Chaput, Benoit Beuselinck, Sylvie Chabaud, Janice Barros-Monteiro, Yann Vano, Bernard Escudier, Catherine Sautès-Fridman, Laurence Albiges, Salem Chouaib
Journal: Clinical Cancer Research (2021)

A minority of patients currently respond to single-agent immune-checkpoint blockade (ICB), and strategies to increase response rates are urgently needed. AXL is a receptor tyrosine kinase commonly associated with drug resistance and poor prognosis in many cancer types, including in clear-cell renal cell carcinoma (ccRCC). Recent experimental cues in breast, pancreatic, and lung cancer models have linked AXL with immune suppression and resistance to antitumor immunity. However, its role in intrinsic and acquired resistance to ICB remains largely unexplored.In this study, tumoral expression of AXL was examined in ccRCC specimens from 316 patients who were metastatic receiving the PD-1 inhibitor nivolumab in the GETUG AFU 26 NIVOREN trial after failure of antiangiogenic therapy. We assessed associations between AXL and patient outcomes following PD-1 blockade, as well as the relationship with various markers, including PD-L1; VEGFA; the immune markers CD3, CD8, CD163, and CD20; and the mutational status of the tumor-suppressor gene von Hippel-Lindau (VHL).Our results show that high AXL-expression level in tumor cells is associated with lower response rates and a trend to shorter progression-free survival following anti-PD-1 treatment. AXL expression was strongly associated with tumor-PD-L1 expression, especially in tumors with VHL inactivation. Moreover, patients with tumors displaying concomitant PD-L1 expression and high AXL expression had the worst overall survival.Our findings propose AXL as candidate factor of resistance to PD-1 blockade, and provide compelling support for screening both AXL and PD-L1 expression in the management of advanced ccRCC.See related commentary by Hahn et al., p. 6619.
Deficits in decision-making induced by parietal cortex inactivation are compensated at two timescales
Authors: Danique Jeurissen, S. Shushruth, Yasmine El-Shamayleh, Gregory D. Horwitz, Michael N. Shadlen
Journal: Neuron (2022)

Perceptual decisions arise through the transformation of samples of evidence into a commitment to a proposition or plan of action. Such transformation is thought to involve cortical circuits capable of computation over timescales associated with working memory, attention, and planning. Neurons in the lateral intraparietal area (LIP) play a role in these functions, and much of what is known about the neurobiology of decision-making has been influenced by studies of LIP and its network of connections. However, the causal role of LIP remains controversial. In this study, we used pharmacological and chemogenetic methods to inactivate LIP in one brain hemisphere of four rhesus monkeys. This inactivation produced biases in decisions, but the effects dissipated despite persistent neural inactivation, implying compensation by unaffected areas. Compensation occurred rapidly within an experimental session and more gradually across sessions. These findings resolve disparate studies and inform the interpretation of focal perturbations of brain function.
Abstract MP22: Myosteatosis Is Associated With Worse Cognition In African Caribbean Women
Authors: Adrianna Acevedo-Fontanez, Ryan Cvejkus, joseph zmuda, Victor Wheeler, Caterina Rosano, Iva Miljkovic, Allison L Kuipers
Journal: Circulation (2022)

Introduction: Skeletal muscle adipose tissue infiltration (i.e. myosteatosis) increases with aging, and is recognized as a major risk factor for cardio-metabolic diseases. While it is known that visceral adiposity is related to dementia and cognitive decline, the relationship between myosteatosis and cognition is not well understood. Such studies are particularly needed among African ancestry women, who have greater myosteatosis and higher burden of Alzheimer’s Disease and Related Dementias compared with White women. Aim: The objective of this study was to assess if, among African Caribbean middle-aged and older women (aged 40-79), myosteatosis is associated with cognitive function. Methods: Data were collected on women (n=481) from the Tobago Health Study. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed; DSST is a fast, reliable and sensitive test that predicts onset of dementia. DSST was administered to participants by trained interviewers; scores ranged from 0 to 81 (lower score indicating cognitive decline). Peripheral Quantitative Computed Tomography (Stratec XCT-2000) was used to measure calf skeletal muscle density (MD), which was used as a proxy measure for the myosteatosis (lower MD reflects more adiposity). Linear regression was used to assess the association of muscle density with cognition and was adjusted for age, education, muscle area, waist circumference, alcohol intake, smoking, walking hours, diabetes and hypertension. Results for the primary predictor of interest (MD) were standardized with effects shown per standard deviation (SD). Results: Mean (SD) DSST scores were 38.8 (13.2). Overall, participants were aged 55.2 years and had a BMI of 30.7 kg/m 2 . Mean (SD) MD was 71.7((5.3) (mg/cm 3 ). As expected, in unadjusted analyses, the strongest predictors of lower DSST scores in these women were older age and lower education, higher waist circumference, diabetes and hypertension. After full adjustment, we found that a one SD increase in MD was associated with a 1.48 increase in DSST score (p-value=0.015). Conclusions: Our findings suggest that in African Caribbean women, greater myosteatosis is associated with slower information processing speed, an early indicator of future dementia risk. Future studies using expanded battery of cognitive tests and longitudinal follow-up are warranted to further advance our understanding of the novel role of myosteatosis in dementia risk among African ancestry women.
Annals Story Slam - Being a Doctor Under Oppression
Authors: Srdjan Nikolovski
Journal: Annals of Internal Medicine (2022)

Web ExclusivesJune 2022Annals Story Slam - Being a Doctor Under OppressionFREESrdjan NikolovskiSrdjan NikolovskiSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0009 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Being a Doctor Under Oppression "Being a Doctor Under Oppression," by Dr. Srdjan Nikolovski (Duration 5:54)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Srdjan NikolovskiCorresponding Author: Srdjan Nikolovski; e-mail, srdjannikolovski@gmail.com.This article was published at Annals.org on 29 April 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: SS1 ePublished: 29 April 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...
Abstract 022: Association Of Nutritionally-Rich Plant-Centered Diets With Gut Microbial Diversity And Composition Columbia Heart Failure-Microbiome Study
Authors: Yuni Choi, Melana Yuzefpolskaya, Bruno Bohn, Rebecca Molinsky, Alberto Pinsino, Lorenzo Braghieri, Abigail Johnson, Daniel Duprez, Paolo C Colombo, David R Jacobs, Ryan Demmer
Journal: Circulation (2022)

Introduction: A plant-centered diet is related to lower risk of cardiovascular disease. However, its association with the gut microbiome has not been well studied in populations with heart failure (HF), and mechanisms linking diet to improved outcomes among HF patients are poorly understood. Hypothesis: Consuming a more nutritionally-rich plant-centered diet is associated with increased microbial alpha diversity and with favorable taxonomic composition and features as compared to consuming less plant-centered diets. Methods: We conducted a cross-sectional analysis of 152 patients with NYHA class I-IV HF with reduced ejection fraction. Diet was assessed using a food frequency questionnaire. Plant-centered diet quality was evaluated using A Priori Diet Quality Score (APDQS) and the APDQS was classified into quintiles; high scores were characterized by higher consumption of nutritionally-rich plant foods with lower consumption of high-fat meats and unhealthy plant foods. Stool samples were analyzed using 16S rRNA gene sequencing. Associations of the APDQS with alpha (Shannon Index and Inverse Simpson) and beta diversity (defined via Bray-Curtis dissimilarity index) were evaluated by linear regression and permutational multivariate analysis of variance (PERMANOVA), respectively. Negative-binomial regressions using DESeq2 were used to study the association between the APDQS and the relative abundance of specific taxa at the phylum and genus levels. Adjustments for multiple comparisons were performed using the false discovery rate. Results: Mean Shannon Index and Inverse Simpson values were 6.28±0.5 and 407.7±183.37, respectively. Among patients aged &lt;61y, after multivariable adjustment, the APDQS (per 12 units) was associated with higher Shannon Index (0.13±0.05; P for slope=0.007) and Inverse Simpson (46.87±15.5; P for slope=0.004); no associations were observed among those aged ≥ 61y (P for interaction &lt;0.05 for each). APDQS quintiles were not associated with beta-diversity (PERMANOVA, P=0.54). At the genus level, the highest quintile of the ADPQS (vs the lowest quintile) was associated with higher abundance of Enterobacter and lower abundance of Catenibacterium. Conclusions: Consuming nutritionally-rich plant-centered diets was significantly associated with higher gut microbiota diversity in younger HF patients, as well as significantly higher or lower abundance of certain bacterial taxa at the genus level.