tbuckley/cabot-search huggingface dataset:
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy
Authors: Judith Wienke, Lindy L. Visser, Waleed M. Kholosy, Kaylee M. Keller, Marta Barisa, Evon Poon, Sophie Munnings-Tomes, Courtney Himsworth, Elizabeth Calton, Ana Rodriguez, Ronald Bernardi, Femke van den Ham, Sander R. van Hooff, Yvette A.H. Matser, Michelle L. Tas, Karin P.S. Langenberg, Philip Lijnzaad, Anne L. Borst, Elisa Zappa, Francisca J. Bergsma, Josephine G.M. Strijker, Bronte M. Verhoeven, Shenglin Mei, Amira Kramdi, Restuadi Restuadi, Alvaro Sanchez-Bernabeu, Annelisa M. Cornel, Frank C.P. Holstege, Juliet C. Gray, Godelieve A.M. Tytgat, Marijn A. Scheijde-Vermeulen, Marc H.W.A. Wijnen, Miranda P. Dierselhuis, Karin Straathof, Sam Behjati, Wei Wu, Albert J.R. Heck, Jan Koster, Stefan Nierkens, Isabelle Janoueix-Lerosey, Ronald R. de Krijger, Ninib Baryawno, Louis Chesler, John Anderson, Hubert N. Caron, Thanasis Margaritis, Max M. van Noesel, Jan J. Molenaar
Journal: Cancer Cell (2024)

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model induces CR. In conclusion, our integrative analysis provides promising targets and a rationale for immunotherapeutic combination strategies.
From beer to breadboards: yeast as a force for biological innovation
Authors: Hamid Kian Gaikani, Monika Stolar, Divya Kriti, Corey Nislow, Guri Giaever
Journal: Genome biology (2024)

Abstract The history of yeast Saccharomyces cerevisiae , aka brewer’s or baker’s yeast, is intertwined with our own. Initially domesticated 8,000 years ago to provide sustenance to our ancestors, for the past 150 years, yeast has served as a model research subject and a platform for technology. In this review, we highlight many ways in which yeast has served to catalyze the fields of functional genomics, genome editing, gene–environment interaction investigation, proteomics, and bioinformatics—emphasizing how yeast has served as a catalyst for innovation. Several possible futures for this model organism in synthetic biology, drug personalization, and multi-omics research are also presented.
A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004)
Authors: Caicun Zhou, Yanping Hu, Ekaterine Arkania, Saadettin Kilickap, Kejing Ying, Fei Xu, Lin Wu, Xiang Wang, Maksym Viguro, Tamta Makharadze, Hongmei Sun, Feng Luo, Jianhua Shi, Aimin Zang, Yueyin Pan, Zhendong Chen, Zhongyao Jia, Vladimer Kuchava, Ping Lu, Ling Zhang, Ying Cheng, Wenying Kang, Qingyu Wang, Haoyu Yu, Jing Li, Jun Zhu
Journal: Cancer Cell (2024)
A Novel Conductive Polypyrrole‐Chitosan Hydrogel Containing Human Endometrial Mesenchymal Stem Cell‐Derived Exosomes Facilitated Sustained Release for Cardiac Repair
Authors: Changping Yan, Xinzhu Wang, Qi Wang, Haiyan Li, Huifang Song, Jingli Zhou, Zexu Peng, Wenjuan Yin, Xuemei Fan, Kun Yang, Bingrui Zhou, Yuxiang Liang, Zengyu Jiang, Yuwei Shi, Sanyuan Zhang, Sheng He, Ren‐Ke Li, Jun Xie
Journal: Advanced Healthcare Materials (2024)

Abstract Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)‐derived exosomes (hEMSC‐Exo) into poly‐pyrrole‐chitosan (PPY‐CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY‐CHI/hEMSC‐Exo, compared to untreated controls, PPY‐CHI, or hEMSC‐Exo alone, alleviates H 2 O 2 ‐induced apoptosis and promotes tubule formation, while in vivo, PPY‐CHI/hEMSC‐Exo improves post‐MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3‐kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY‐CHI/hEMSC‐Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY‐CHI/hEMSC‐Exo synergistically combines the cardiac regenerative capabilities of hEMSC‐Exo with the conductive properties of PPY‐CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long‐term exosome release and sustained application of their beneficial effects.
Opportunities in Assessing and Regulating Organohalogen Flame Retardants (OFRs) as a Class in Consumer Products
Authors: Xinrong Chen, Linda S. Birnbaum, Michael A. Babich, Jacob de Boer, Kimberly W. White, Stanley Barone, Cathy Fehrenbacher, Heather M. Stapleton
Journal: Environmental Health Perspectives (2024)

In 2015, the U.S. Consumer Product Safety Commission (CPSC) received and then, in 2017, granted a petition under the Federal Hazardous Substances Act to declare certain groups of consumer products as banned hazardous substances if they contain nonpolymeric, additive organohalogen flame retardants (OFRs). The petitioners asked the CPSC to regulate OFRs as a single chemical class with similar health effects. The CPSC later sponsored a National Academy of Sciences, Engineering, and Medicine (NASEM) report in 2019, which ultimately identified 161 OFRs and grouped them into 14 subclasses based on chemical structural similarity. In 2021, a follow-up discussion was held among a group of scientists from both inside and outside of the CPSC for current research on OFRs and to promote collaboration that could increase public awareness of CPSC work and support the class-based approach for the CPSC's required risk assessment of OFRs.
Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With <i>ERBB2</i>-Positive Advanced Breast Cancer and Brain Metastases
Authors: Zhaozhi Yang, Jin Meng, Xin Mei, Miao Mo, Qin Xiao, Xu Han, Li Zhang, Wei Shi, Xingxing Chen, Jinli Ma, Joshua Palmer, Zhimin Shao, Zhen Zhang, Xiaoli Yu, Xiaomao Guo
Journal: JAMA Oncology (2024)

The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear.
Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice
Authors: Nabil E. Boutagy, Ana Gamez-Mendez, Joseph W.M. Fowler, Hanming Zhang, Bal K. Chaube, Enric Esplugues, Andrew Kuo, Sungwoon Lee, Daiki Horikami, Jiasheng Zhang, Kathryn M. Citrin, Abhishek K. Singh, Brian G. Coon, Monica Y. Lee, Yajaira Suarez, Carlos Fernandez-Hernando, William C. Sessa
Journal: Journal of Clinical Investigation (2024)

Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) is not known. In this study, we showed that deletion of the enzyme, adipose triglyceride lipase (ATGL) in the endothelium, led to neutral lipid accumulation in vessels and impaired endothelial dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD impacts endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.
Progressive Massive Fibrosis Identified at Federally Funded Black Lung Clinics in the US
Authors: Drew A. Harris, Kirsten S. Almberg, David J. Blackley, Robert A. Cohen, Chesnee Edwards, Bradley Johnson, Noemi B. Hall
Journal: JAMA (2024)

This study of US Black Lung Clinics (established to treat coal miners) reports the prevalence of progressive massive fibrosis identified through June 2023.
Exposure to Residential Green Space and Bone Mineral Density in Young Children
Authors: Hanne Sleurs, Ana Inês Silva, Esmée M. Bijnens, Yinthe Dockx, Martien Peusens, Leen Rasking, Michelle Plusquin, Tim S. Nawrot
Journal: JAMA Network Open (2024)

Importance Bone mass accrual is influenced by environmental and lifestyle factors. Targeted interventions at the early stages of life might decrease fracture and/or osteoporosis risk later in life. Objective To investigate whether early-life exposure to residential surrounding green space is associated with a change in bone mineral density in young children. Design, Setting, and Participants In this prospective birth cohort study (ENVIRONAGE [Environmental Influence on Aging in Early Life]), mother-child pairs from Flanders, Belgium, were recruited at birth and followed up for 4 to 6 years, between October 1, 2014, and July 31, 2021. Data analysis was conducted between January and February 2022. Exposures Green space was estimated for high green (&amp;amp;gt;3 m vegetation height), low green (≤3 m vegetation height ), and total green (sum of high and low) within several radii (100-3000 m) around the residence after geocoding of the addresses. Main Outcomes and Measures Radial bone mineral density was assessed using quantitative ultrasound measurement at follow-up, measured as the mean of the axially transmitted speed of sound in meters per second. Multiple linear and logistic regression models were used while accounting for relevant covariates and potential confounders. Results The study population comprised 327 children (180 [55.0%] female; mean [SD] age, 4.6 [0.4] years at the follow-up evaluation). Early-life exposure to residential green space was associated with increased childhood bone health. An IQR increment in total green (21.2%) and high green (19.9%) space within 500 m was associated with an increase of 27.38 m/s (95% CI, 9.63-45.13 m/s) and 25.30 m/s (95% CI, 7.93-42.68 m/s) in bone mineral density, respectively. Additionally, an IQR increase in total (25.2%) and high (23.2%) green space within 1000 m was associated with a 67% (odds ratio, 0.33; 95% CI, 0.17-0.61) and 61% (odds ratio, 0.39; 95% CI, 0.18-0.75) lower risk of having a bone density lower than the sex-specific 10th percentile (3567.6 m/s for girls and 3522.8 m/s for boys). Conclusions and Relevance In this study of children aged 4 to 6 years, higher bone mineral density and a lower risk of having low bone density were associated with higher residential green space exposure during childhood. These findings highlight the importance of early-life exposure to residential green space on bone health during critical periods of growth and development, with long-term implications.
The Role of Circadian Rhythms and Sleep in Anorexia Nervosa
Authors: Hannah Wilcox, Valentina Paz, Richa Saxena, John W. Winkelman, Victoria Garfield, Hassan S. Dashti
Journal: JAMA Network Open (2024)

Importance Observational studies have associated anorexia nervosa with circadian rhythms and sleep traits. However, the direction of causality and the extent of confounding by psychosocial comorbidities in these associations are unknown. Objectives To investigate the association between anorexia nervosa and circadian and sleep traits through mendelian randomization and to test the associations between a polygenic risk score (PRS) for anorexia nervosa and sleep disorders in a clinical biobank. Design, Setting, and Participants This genetic association study used bidirectional 2-sample mendelian randomization with summary-level genetic associations between anorexia nervosa (from the Psychiatric Genomics Consortium) and chronotype and sleep traits (primarily from the UK Biobank). The inverse-variance weighted method, in addition to other sensitivity approaches, was used. From the clinical Mass General Brigham (MGB) Biobank (n = 47 082), a PRS for anorexia nervosa was calculated for each patient and associations were tested with prevalent sleep disorders derived from electronic health records. Patients were of European ancestry. All analyses were performed between February and August 2023. Exposures Genetic instruments for anorexia nervosa, chronotype, daytime napping, daytime sleepiness, insomnia, and sleep duration. Main Outcomes and Measures Chronotype, sleep traits, risk of anorexia nervosa, and sleep disorders derived from a clinical biobank. Results The anorexia nervosa genome-wide association study included 16 992 cases (87.7%-97.4% female) and 55 525 controls (49.6%-63.4% female). Genetic liability for anorexia nervosa was associated with a more morning chronotype (β = 0.039; 95% CI, 0.006-0.072), and conversely, genetic liability for morning chronotype was associated with increased risk of anorexia nervosa (β = 0.178; 95% CI, 0.042-0.315). Associations were robust in sensitivity and secondary analyses. Genetic liability for insomnia was associated with increased risk of anorexia nervosa (β = 0.369; 95% CI, 0.073-0.666); however, sensitivity analyses indicated bias due to horizontal pleiotropy. The MGB Biobank analysis included 47 082 participants with a mean (SD) age of 60.4 (17.0) years and 25 318 (53.8%) were female. A PRS for anorexia nervosa was associated with organic or persistent insomnia in the MGB Biobank (odds ratio, 1.10; 95% CI, 1.03-1.17). No associations were evident for anorexia nervosa with other sleep traits. Conclusions and Relevance The results of this study suggest that in contrast to other metabo-psychiatric diseases, anorexia nervosa is a morningness eating disorder and further corroborate findings implicating insomnia in anorexia nervosa. Future studies in diverse populations and with subtypes of anorexia nervosa are warranted.
Review of Racial and Ethnic Representation of Participants Enrolled in Pediatric Clinical Trials of Oncology Drugs Conducted Through FDA Written Requests
Authors: Lola A. Fashoyin-Aje, Alemayehu Y. Akalu, Jessica Boehmer, Richard Pazdur, Martha Donoghue, Gregory H. Reaman
Journal: JAMA Oncology (2024)

The Best Pharmaceuticals for Children Act states that in issuing a written request (WR), the US Food and Drug Administration (FDA) shall consider the adequate representation (eg, proportionate to the disease population) of children from racial and ethnic minority populations. If the terms of the WR are fulfilled, the FDA may grant an additional 6 months of exclusivity for any unexpired patents and exclusivities attached to approved indications.
Neutrophil infiltration in allergic contact dermatitis to nickel
Authors: Anders B Funch, Malin Glindvad Ahlström, Jeanne D Johansen, Carsten Geisler, Charlotte M Bonefeld
Journal: British Journal of Dermatology (2024)

Allergic contact dermatitis (ACD) is traditionally recognized as a T-cell-mediated delayed-type hypersensitivity reaction. However, many patients with ACD have been reported to experience rapid-onset ACD reactions within hours of re-exposure on skin areas previously exposed to the contact allergen. In this study, three nickel-allergic patients were patch tested for nickel twice at the same skin site over 21 days. The results demonstrated that neutrophils are rapidly recruited to the skin sites previously exposed to nickel, leading to the rapid onset of ACD. Considering that many patients with ACD are frequently re-exposed to contact allergens on the same skin areas in their daily lives, we propose that mechanisms involved in neutrophil recruitment could be potential targets for future ACD treatment.
Hope during somber times: a defining moment
Authors: Benjamin W Corn, David B Feldman
Journal: JNCI Journal of the National Cancer Institute (2024)

In addition to the diverse educational materials the National Cancer Institute provides to patients, caregivers, and health-care professionals, the NCI maintains an online dictionary that provides concise definitions of terms used in modern oncology. The dictionary is regarded as a valuable data reserve because it is updated frequently and employs language that facilitates comprehension among lay users and professionals alike. In this commentary, we call attention to the absence of the word hope as an entry in this important digital resource. Moreover, we propose not only including the concept of hope in this vital reference text but also basing its meaning on C. R. Snyder's model of "hope theory," which stresses the importance of 3 entities: goals, pathways thinking, and agency. Finally, we argue that hope can be taught as a skill to relevant stakeholders (eg, patients, caregivers, and health-care professionals) through brief workshops that have recently been expanded from in-person encounters to virtual platforms revolving around a user-friendly mobile app called "Hopetimize."
Defining the Role of Extrachromosomal DNA Amplifications in Medulloblastoma
Authors: Dacheng Zhao, Roel G.W. Verhaak
Journal: Cancer Research (2024)

Abstract Circular extrachromosomal DNA (ecDNA), a common mechanism of oncogene amplification, has been identified as a major contributor to intratumoral heterogeneity and patient outcomes. In a recent publication in Nature Genetics, Chapman and colleagues further explored the role of ecDNA in the context of medulloblastoma. Using whole-genome sequencing, they found that 18% of the patients carry ecDNA amplification across a 468 medulloblastoma patient cohort. The presence of ecDNA was associated with worse survival. Single-cell FISH imaging and multiomic sequencing revealed that ecDNA copy number displayed a cell-to-cell variability within the sample, contributing to tumor heterogeneity. Furthermore, through sequencing and CRISPRi experiments, the authors uncovered frequent enhancer rewiring events on ecDNA that drive proliferation.
Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study
Authors: So-Ryoung Lee, Hyo-Jeong Ahn, Eue-Keun Choi, Sang-Hyun Park, Kyung-Do Han, Seil Oh, Gregory Y.H. Lip
Journal: Clinical Gastroenterology and Hepatology (2024)
Prognosis of Merkel cell carcinoma patients with autoimmune disorders, other types of immune dysfunction, or immunocompetent status: Analysis of 762 patients
Authors: Song Y. Park, Daniel S. Hippe, Lauren Zawacki, Marika Bierma, Shailender Bhatia, Paul Nghiem, Lisa C. Zaba, Namrata Singh
Journal: Journal of the American Academy of Dermatology (2024)
Solar urticaria involves rapid mast cell STAT3 activation and neutrophil recruitment, with FcεRI as an upstream regulator
Authors: Kirsty J. Rutter, Michael Peake, Nathan J. Hawkshaw, Rachel Scholey, Silvia Bulfone-Paus, Peter S. Friedmann, Mark D. Farrar, Lesley E. Rhodes
Journal: Journal of Allergy and Clinical Immunology (2024)

Background Solar urticaria is a rare photodermatosis characterised by rapid onset sunlight-induced urticaria, but its pathophysiology is not well understood. Objective To define the cutaneous cellular and molecular events in the evolution of solar urticaria following its initiation by solar simulated ultraviolet radiation (SSR), and compare with healthy controls (HC). Methods Cutaneous biopsies were taken from unexposed skin and skin exposed to a single low (physiological) dose of SSR, at 30 minutes, 3 and 24 hours post-exposure, in n=6 solar urticaria patients and n=6 HC. Biopsies were assessed by immunohistochemistry and bulk RNA-sequencing analysis. Results In solar urticaria, there was enrichment of several innate immune pathways, with striking early involvement of neutrophils, which was not observed in HC. Multiple pro-inflammatory cytokine and chemokine genes were upregulated (including IL20, IL6, CXCL8) or identified as upstream regulators (including TNF, IL1β, IFNγ). IgE and FcεR1 were identified as upstream regulators, and phosphorylated STAT3 expression in mast cells was increased in solar urticaria at 30 minutes and 3 hours post-SSR exposure, suggesting a mechanism of mast cell activation. Clinical resolution of solar urticaria by 24 hours mirrored resolution of inflammatory gene signature profiles. Comparison with available datasets of chronic spontaneous urticaria showed transcriptomic similarities relating to immune activation but several transcripts were identified solely in solar urticaria including CXCL8 and CSF2/3. Conclusions Solar urticaria is characterised by rapid STAT3 activation in mast cells and involvement of multiple chemotactic and innate inflammatory pathways, with FcεR1 engagement indicated as an early event.
Circulation Research and 70 Years of Basic Science: Examining the Past and Looking Forward to the Future
Authors: Jane E. Freedman
Journal: Circulation Research (2024)

irculation Research has undergone a remarkable evolution over the past 70 years.From its beginnings in 1953 to the present day, Circulation Research has been at the forefront of basic and translational cardiovascular research, leading the way in disseminating groundbreaking discoveries, innovations, and advancements in the fields of cardiovascular and stroke research.The journal was established by the American Heart Association soon after its sister publication, Circulation, was published in 1950.Until this time, most basic research was published in specialized and physiology journals.The American Heart Association established a Scientific Council to direct its research programs and, in 1951, the Scientific Council proposed the initiation of a journal dedicated to the publication of basic cardiovascular research. 1In 1952, Carl J. Wiggers was selected to be the first Editor of Circulation Research, and, over the past 70 years, the journal has had 12 Editors-in-Chief (Table ) stewarding it through evolving changes in science.Upon publication, the American Heart Association announced that Circulation Research was to be "the authoritative new journal for investigators of the basic sciences as they apply to the heart and circulation-anatomy, biology, biochemistry." 2 In its very early years, Circulation Research allowed cardiovascular researchers an opportunity to share their basic and mechanistic experimental findings.The journal was central in advancing partnerships between researchers and institutions as well as becoming a scientific home for the basic cardiovascular research community.ManyThe American Heart Association celebrates its 100 th anniversary in 2024.