tbuckley/cabot-search huggingface dataset:
Dual-responsive polypeptide nanoparticles attenuate tumor-associated stromal desmoplasia and anticancer through programmable dissociation
Authors: Pei-Hsuan Hsieh, Wei-Yuan Huang, Huan-Chih Wang, Chen-Hsiang Kuan, Ting-Yun Shiue, Yunching Chen, Tzu-Wei Wang
Journal: Biomaterials (2022)
THE APPLICATION OF A NOVEL AI-BASED ALGORITHM IN IMPLANTABLE LOOP RECORDERS, REDUCTION IN FALSE POSITIVE ATRIAL ARRHYTHMIA EVENT EPISODES WITHOUT IMPACTING TIME TO FIRST EVENT DETECTION
Authors: Eliot Crespin, Jean-Luc Bonnet, Issam Ibnouhsein, Arnaud Rosier, Kevin R. Campbell, Niraj Varma
Journal: Journal of the American College of Cardiology (2022)
The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation
Authors: Raphael Carapito, Ismail Aouadi, Martin Verniquet, Meiggie Untrau, Angélique Pichot, Thomas Beaudrey, Xavier Bassand, Sébastien Meyer, Loic Faucher, Juliane Posson, Aurore Morlon, Irina Kotova, Florent Delbos, Alexandre Walencik, Alice Aarnink, Anne Kennel, Caroline Suberbielle, Jean-Luc Taupin, Benedict M Matern, Eric Spierings, Nicolas Congy-Jolivet, Arnaud Essaydi, Peggy Perrin, Antoine Blancher, Dominique Charron, Nezih Cereb, Myriam Maumy-Bertrand, Frédéric Bertrand, Valérie Garrigue, Vincent Pernin, Laurent Weekers, Maarten Naesens, Nassim Kamar, Christophe Legendre, Denis Glotz, Sophie Caillard, Marc Ladrière, Magali Giral, Dany Anglicheau, Caner Süsal, Seiamak Bahram
Journal: Nature Medicine (2022)

Abstract The identity of histocompatibility loci, besides human leukocyte antigen ( HLA ), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45–3.11; P &lt; 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94–7.39; P &lt; 0.001; HR, 9.92; 95% CI: 7.43–13.20; P &lt; 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31–199.41; P = 0.002; HR, 82.67; 95% CI: 33.67–202.97; P &lt; 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05–1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02–2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.
SERUM GLIAL FIBRILLARY ACIDIC PROTEIN INDICATES COGNITIVE DEFICITS IN PATIENTS WITH HEART FAILURE - FINDINGS FROM THE COGNITION.MATTERS-HF STUDY
Authors: Jan Traub, Markus Otto, Roxane Sell, György Homola, Petra Steinacker, Patrick Oeckl, Caroline Morbach, Stefan Frantz, Mirko Pham, Stefan Stoerk, Guido Stoll, Anna Frey
Journal: Journal of the American College of Cardiology (2022)
LEFT VENTRICULAR APICAL THROMBUS IN ACUTE MYOCARDIAL INFARCTION WITH ST-SEGMENT ELEVATION AND CARDIOGENIC SHOCK: RELATIVE OR ABSOLUTE CONTRAINDICATION IN VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION?
Authors: Isis Guadalupe Montalvo Ocotoxtle, Luis Augusto Baeza Herrera, Gustavo Rojas Velasco, Cristopher Candido Sanchez Rodriguez, Lizeth Escobar, Angel Ramos Enriquez, Efren Melano Carranza, Daniel Manzur Sandoval, Eduardo Rafael Bucio Reta
Journal: Journal of the American College of Cardiology (2022)
Gain-of-function <i>IKZF1</i> variants in humans cause immune dysregulation associated with abnormal T/B cell late differentiation
Authors: Akihiro Hoshino, David Boutboul, Yuan Zhang, Hye Sun Kuehn, Jerôme Hadjadj, Nihal Özdemir, Tiraje Celkan, Christoph Walz, Capucine Picard, Christelle Lenoir, Nizar Mahlaoui, Christoph Klein, Xiao Peng, Antoine Azar, Erin Reigh, Morgane Cheminant, Alain Fischer, Frédéric Rieux-Laucat, Isabelle Callebaut, Fabian Hauck, Joshua Milner, Sergio D. Rosenzweig, Sylvain Latour
Journal: Science Immunology (2022)

IKZF1/IKAROS is a key transcription factor of lymphocyte development expressed throughout hematopoiesis. Heterozygous germline IKZF1 haploinsufficient (IKZF1HI) and dominant-negative (IKZF1DN) variants in humans cause B cell immune deficiency and combined immunodeficiency. Here, we identified previously unidentified heterozygous IKZF1 variants (R183C/H) located in the DNA binding domain in eight individuals with inflammatory, autoimmune, allergic symptoms, and abnormal plasma cell (PC) proliferation. Leukocytes of patients exhibited specific defects including impaired IL-2 production by T cells, T helper (TH) skewing toward TH2, low numbers of regulatory T cells (Treg), eosinophilia, and abnormal PC proliferation. In contrast to IKZF1HI and IKZF1DN, IKZF1R183H/C proteins showed increased DNA binding associated with increased gene expression of TH2 and PC differentiation, thus demonstrating that IKZF1R183H/C behave as gain-of-function (GOF) alleles. In vitro treatment with lenalidomide, known to degrade IKZF1, corrected TH2 and PC abnormalities caused by IKZF1R183H/C. These data extend the spectrum of pathological mechanisms associated with IKZF1 deficiencies and highlight the role of IKZF1 in late lymphoid differentiation stages.
Oncogenic and Tumor-Suppressive Functions of the RNA Demethylase FTO
Authors: Hidde R. Zuidhof, Cornelis F. Calkhoven
Journal: Cancer Research (2022)

Abstract The epitranscriptome represents the more than 140 types of chemically varying and reversable RNA modifications affecting RNA fate. Among these, the most relevant for this review are the mRNA modifications N6-methyladenosine and N6,2′-O-dimethyladenosine. Epitranscriptomic mRNA biology involves RNA methyltransferases (so-called “writers”), RNA demethylases (“erasers”), and RNA-binding proteins (“readers”) that interact with methylation sites to determine the functional outcome of the modification. In this review, we discuss the role of a specific RNA demethylase encoded by the fat mass and obesity–associated gene (FTO) in cancer. FTO initially became known as the strongest genetic link for human obesity. Only in 2010, 16 years after its discovery, was its enzymatic function as a demethylase clarified, and only recently has its role in the development of cancer been revealed. FTO functions are challenging to study and interpret because of its genome-wide effects on transcript turnover and translation. We review the discovery of FTO and its enzymatic function, the tumor-promoting and suppressive roles of FTO in selected cancer types, and its potential as a therapeutic target.
American Cancer Society nutrition and physical activity guideline for cancer survivors
Authors: Cheryl L. Rock, Cynthia A. Thomson, Kristen R. Sullivan, Carol L. Howe, Lawrence H. Kushi, Bette J. Caan, Marian L. Neuhouser, Elisa V. Bandera, Ying Wang, Kimberly Robien, Karen M. Basen‐Engquist, Justin C. Brown, Kerry S. Courneya, Tracy E. Crane, David O. Garcia, Barbara L. Grant, Kathryn K. Hamilton, Sheri J. Hartman, Stacey A. Kenfield, Maria Elena Martinez, Jeffrey A. Meyerhardt, Larissa Nekhlyudov, Linda Overholser, Alpa V. Patel, Bernardine M. Pinto, Mary E. Platek, Erika Rees‐Punia, Colleen K. Spees, Susan M. Gapstur, Marjorie L. McCullough
Journal: CA A Cancer Journal for Clinicians (2022)

Abstract The overall 5‐year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence‐based, cancer‐specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer‐specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta‐analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health‐related behaviors and comorbidities, long‐term sequelae and patient‐reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.
Abstract P5-17-06: P38 kinase as a therapeutic target to reverse an immune suppressive tumor microenvironment in metastatic breast cancer
Authors: Priyanka Rajan, Justin Zonneville, Sean Colligan, Scott Abrams, Andrei Bakin
Journal: Cancer Research (2022)

Abstract The immune suppressive tumor microenvironment (TME) in metastatic breast cancer (MBC) limits the benefits of immunotherapy with immune checkpoint inhibitors (ICIs). In particular, the primary TME drives the expansion and recruitment of immune suppressive myeloid cell populations, such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Treatments targeting these populations can potentially improve the efficacy of ICI therapy. To that end, our published and new findings have revealed that the p38 Mitogen-Activated Protein Kinase (MAPK) contributes to the expansion and mobilization of TAMs and MDSCs. Further, we found that pharmacological blockade of p38 decreased metastasis and increased the levels of CD8+ T cells while decreasing TAMs in the primary TME. Depletion of PMN-MDSCs, a major MDSC subset, was accompanied by reduced TAM infiltration and phenocopied the anti-metastatic effects of p38 blockade. Next, we explored the impact of p38 blockade on the composition and functionality of the immune populations in the primary TME by using single-cell RNA-sequencing. We found that p38 blockade increased levels of Irf8+ monocytic populations, indicating a decrease in immune-suppressive properties of the TME. Notably, p38 blockade increased the expression of factors related to the activation of CD8+ cytotoxic T lymphocytes, i.e., Jchain, Icos, and Cd137. Thus, our data indicate that p38 blockade alters the immune landscape within the primary TME and favors an antitumor immune response. Our data also suggest that the p38 kinase controls the production of tumor-derived factors (TDFs) which facilitate the recruitment of those pro-tumor myeloid populations. Thus, we explored this p38-TDF-myeloid axis by using trans-well migration assays. We tested the migration of the monocyte-like cell line RAW 264.7 in response to tumor-conditioned media prepared from tumor cells treated with or without the p38 inhibitor, Ralimetinib. Our data showed that the migration of RAW 264.7 cells was significantly diminished towards the conditioned media from tumor cells treated with the p38 inhibitor or from tumor cells with a genetic inactivation of p38α by CRISPR/Cas9 compared to the corresponding controls. Altogether, our studies demonstrate that p38 kinase is a potential therapeutic target, which reshapes the immune suppressive contexture of TME in MBC to improve antitumor immunity. Citation Format: Priyanka Rajan, Justin Zonneville, Sean Colligan, Scott Abrams, Andrei Bakin. P38 kinase as a therapeutic target to reverse an immune suppressive tumor microenvironment in metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-17-06.
Should covid-19 vaccines and drugs be “not for profit”?
Authors: Mohga Kamal-Yanni, Thomas Cueni
Journal: BMJ (2022)

HIV, Ebola, and now covid-19: if a pandemic is not the time for governments to retain control by sharing knowledge and waiving intellectual property rules, then when, asks <b>Mohga Kamal-Yanni</b>. But <b>Thomas Cueni</b> says that debates about prices and profit are straw men to the real question of why the world failed to provide equitable access to covid vaccines
Association of Obesity, Diabetes, and Alcohol Use With Liver Fibrosis Among US Adults With Hepatitis C Virus Infection
Authors: Alexandra L. Migdal, Ram Jagannathan, Emad Qayed, Kenneth Cusi, Rozalina G. McCoy, Francisco J. Pasquel, Lesley S. Miller
Journal: JAMA Network Open (2022)

This cross-sectional study examines the association of obesity, diabetes, and alcohol use with liver fibrosis among treatment-naive US adults with hepatitis C virus infection seen at a safety-net hospital in Atlanta, Georgia.
Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish
Authors: Sin Man Lam, Jie Li, Huan Sun, Weining Mao, Zongmin Lu, Qingshuo Zhao, Chao Han, Xia Gong, Binhua Jiang, Gek Huey Chua, Zhenwen Zhao, Fanwei Meng, Guanghou Shui
Journal: Molecular Biology and Evolution (2022)

Abstract Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism is associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated docosahexaenoic acid (DHA) biosynthesis via the Δ4 desaturase pathway led to reductions in DHA-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, and acox1). Development of fatty livers was observed in cavefish; likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla, and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes as reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1, and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates nonessential morphological and behavioral traits and giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.
Growth differentiation factor-15 preserves Klotho expression in acute kidney injury and kidney fibrosis
Authors: Lara Valiño-Rivas, Leticia Cuarental, Maria I. Ceballos, Arancha Pintor-Chocano, Maria Vanessa Perez-Gomez, Ana B. Sanz, Alberto Ortiz, Maria Dolores Sanchez-Niño
Journal: Kidney International (2022)
期刊一览
Authors: Sandeep Ravindran
Journal: Ophthalmology (2022)

Rein (p. 369) 等通过分析二手数据来源，以估算美国视觉损害（vision loss [VL]）的经济负担。视觉损害成本于2017年估计为1342亿美元，包括987亿美元直接成本和355亿美元间接成本，VL的增量成本为每人16838美元。超过66%负担来自疗养院护理（418亿美元），其他医疗护理（309亿美元），及减少的劳动力参与度（162亿美元）。非正式护理为0-18岁人群的最大负担来源，减少的劳动力参与度为19至64岁人群的最大负担来源，护理院成本为65岁及以上人群的 最大负担来源。纽约州、康涅狄格州、马萨诸塞州、罗德岛州和佛蒙特州的VL人均成本最高。作者得出结论，VL给美国带来巨大经济负担。 在一项横断面研究中，Shah (p. 388) 等就青光眼患者中最能反映视野（visual field [VF]）损害的患者报告症状进行研究。对95名可疑青光眼及75名青光眼患者进行分析，发现一部分特定患者报告症状可用于解释大约三分之二VF损害差异。与VF损害程度相关的特定症状包括视物模糊，周边视力范围小，片状缺失、其中一眼视力较差、视力随时间恶化。此外，患者报告症状较视网膜神经纤维层厚度更能预测VF损害差异。研究人员得出结论，某些特定的患者报告症状可能有助于评估VF损害，并提示该信息有助于患者与医生的沟通。 Douglas (p. 438) 等报告了开放标记扩展OPTIC-X研究的结果，该研究评估了teprotumumab对合并甲状腺眼病（thyroid eye disease [TED]）但治疗无反应或在OPTIC 3期研究中出现病情发作患者治疗及重新治疗的安全性和有效性。在OPTIC-X中使用teprotumumab治疗时，37名原接受安慰剂治疗的OPTIC患者中33名（89.2%）眼球突出得以改善，与OPTIC研究效果相当。大多数接受teprotumumab重新治疗的患者眼球突出及复视的情况得到临床显著性缓解，且病情较长的患者治疗反应与OPTIC研究中接受teprotumumab治疗反应相当。临床指标改善与生活质量提高相关，且长期随访中任何治疗组均未发现新的安全性问题。作者得出结论，teprotumumab可能对较之前报道TED病程更长的患者有效。 Wirta (p. 379) 等进行了一项随机、双盲、空白对照的3期研究，以评估OC-01（伐尼克兰溶液）鼻内喷雾治疗干眼症患者的效果和安全性。共计758名患者被1:1:1随机分配至50-ml鼻内喷雾剂每日两次0.03 mg OC-01，0.06 mg OC-01，或空白对照治疗组，为期4周。与空白对照相比，OC-01治疗改善患者报告的干眼症症状及自然泪膜形成，更多OC-01治疗患者达到临床有意义的泪液量改善（Schirmer测试评分增加 ≥10-mm）。OC-01耐受度良好，最常见副反应为轻度一过性喷嚏。作者得出结论，OC-01用于治疗干眼症患者耐受性良好，临床有效。 Bhandari (p. 414) 等评估了AREDS2研究前瞻性队列中，随访10年受试者白内障手术后发生迟发性年龄相关性黄斑变性（age-related macular degeneration [AMD]）的风险。共计1195名受试者的1767例符合入选条件患眼接受白内障手术，随访期间1524名受试者的1981例患眼发生迟发性AMD。Cox回归模型显示白内障术后迟发性AMD发生风险无增高，右眼风险比为0.96，左眼风险比为1.05。逻辑回归模型发现白内障手术后发生迟发性AMD风险统计学非显著，风险比为0.92。配对分析中，迟发性AMD见于408例接受白内障手术患眼及429例有晶体眼对照，比值比为0.92。作者得出结论，10年随访过程中，AREDS2受试者中接受白内障手术未增加迟发性AMD发病风险。 This Issue at a GlanceOphthalmologyVol. 129Issue 4PreviewRein et al ( p. 369 ) analyzed secondary data sources to estimate the economic burden of vision loss (VL) in the United States. Vision loss was estimated to have cost $134.2 billion in 2017, with $98.7 billion in direct costs and $35.5 billion in indirect costs, and an incremental cost of $16 838 per person with VL. More than 66% of the burden resulted from the costs of nursing home care ($41.8 billion), other medical care ($30.9 billion), and reduced labor force participation ($16.2 billion). Informal care was the largest burden component for people 0 to 18 years of age, reduced labor force participation was the largest burden component for people 19 to 64 years of age, and nursing home costs were the largest burden component for people 65 years of age or older. Full-Text PDF
Optimising tuberculosis care for refugees affected by armed conflicts
Authors: Kenneth G Castro, Lucica Ditiu, Suvanand Sahu, Francine Ntoumi, Simon Tiberi, Cecilia M O'Kane, Onno Akkerman, Katerina Manika, Peter Mwaba, Lina Davies Forsman, Eskild Petersen, Eleni Aklillu, Esam I Azhar, Daniela M Cirillo, Giovanni-Battista Migliori, Aula Abbara, Alimuddin Zumla
Journal: The Lancet Respiratory Medicine (2022)
PRIOR TO CANCER TREATMENT, DO WOMEN WITH BREAST CANCER EXPERIENCE REDUCED AORTIC DISTENSIBILITY IN THE ABSENCE OF HYPERTENSION?
Authors: Suhas Suddala, Nathaniel S. O'Connell, Ralph B. D'Agostino, Jennifer H. Jordan, Giselle C. Meléndez, Mary Helen Hackney, Amy Ladd, Daniel Miller, Glenn J. Lesser, Kathryn E. Weaver, Alexander R. Lucas, Alexandra Thomas, W. Gregory Hundley
Journal: Journal of the American College of Cardiology (2022)
NOVEL TOOL AUTOMATICALLY DIFFERENTIATES WIDE COMPLEX TACHYCARDIAS: CAN IT IMPROVE PHYSICIAN INTERPRETATION ACCURACY AND CONFIDENCE?
Authors: Anthony Kashou, Peter Noseworthy, Jacob Colin Jentzer, Alexandria Roy, Helayna Abraham, Philip Sang, Ellen Kronzer, Sara Inglis, Joshua Rezkalla, Raghav Julakanti, Petar Saric, Nikita Rafie, Abhishek Deshmukh, Christopher DeSimone, Samuel J. Asirvatham, Adam Maurice May
Journal: Journal of the American College of Cardiology (2022)
HSR22-162: Budget Impact Analysis of Abemaciclib in Combination With Endocrine Therapy (ET) in Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-), Node-Positive Early Breast Cancer (EBC) at High Risk of Recurrence and Ki-67 Score ≥20%
Authors: Gregory L Price, Frank N Cinfio, Pamela A Martin, Alexandra S Vitko, Mark E Boye, Angelo DeLuca, Christopher A Bly, Chelsea Manion, Jacqueline Brown
Journal: Journal of the National Comprehensive Cancer Network (2022)

"HSR22-162: Budget Impact Analysis of Abemaciclib in Combination With Endocrine Therapy (ET) in Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-), Node-Positive Early Breast Cancer (EBC) at High Risk of Recurrence and Ki-67 Score ≥20%" published on 31 Mar 2022 by National Comprehensive Cancer Network.
An Intelligent Nanovehicle Armed with Multifunctional Navigation for Precise Delivery of Toll‐Like Receptor 7/8 Agonist and Immunogenic Cell Death Amplifiers to Eliminate Solid Tumors and Trigger Durable Antitumor Immunity
Authors: Yanyun Hao, Hui Li, Huajun Zhao, Yutong Liu, Xiaoyan Ge, Xia Li, Hongfei Chen, Ailu Yang, Jing Zou, Xue Li, Xuechun Sun, Xinke Zhang, Xiao Wang, Zepeng Li, Qilu Zhang, Hao Wu, Guan Wang, Jian Zhang, Bruno G. De Geest, Zhiyue Zhang
Journal: Advanced Healthcare Materials (2022)

Abstract Cancer immunotherapy is revolutionary in oncology and hematology. However, a low response rate restricts the clinical benefits of this therapy owing to inadequate T lymphocyte infiltration and low delivery efficiency of immunotherapeutic drugs. Herein, an intelligent nanovehicle (folic acid (FA)/1‐(4‐(aminomethyl) benzyl)‐2‐butyl‐1H‐imidazo[4,5‐c]quinolin‐4‐amine (IMDQ)‐oxaliplatin (F/IMO)@CuS) armed with multifunctional navigation is designed for the accurate delivery of cargoes to tumor cells and dendritic cells (DCs), respectively. The nanovehicle is based on a near infrared‐responsive inorganic CuS nanoparticles, acting as a photosensitizer and carrier of the chemotherapeutic agent oxaliplatin, and enters tumor cells owing to the presence of folic acid on the surface of CuS upon intratumoral injection. Furthermore, a toll‐like receptor (TLR) 7/8 agonist‐conjugated polymer, anchored on the surface of CuS, is modified with mannose to bind with DCs in the tumor microenvironment. Upon exposure to laser irradiation, nanovehicles disassemble, releasing oxaliplatin, to ablate tumor cells and amplify immunogenic cell death in combination with photothermal therapy. Mannose‐modified polymer‐TLR7/8 agonist conjugates are subsequently exposed, leading to the activation of DCs and proliferation of T cells. Collectively, these intelligent nanovehicles reduce tumor burden, exert a robust antitumor immune response, and generate long‐term immune protection to prevent tumor recurrence.
Adversity and Opportunity—The Pandemic’s Paradoxical Effect on Child Health and Well-being
Authors: Paul H. Wise, Lisa J. Chamberlain
Journal: JAMA Pediatrics (2022)

Lydie A. Lebrun-Harris, PhD, MPH; Reem M. Ghandour, DrPH, MPA; Michael D. Kogan, PhD; Michael D. Warren, MD, MPH