tbuckley/cabot-search huggingface dataset:
Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche
Authors: Takuo Emoto, Jessie Lu, Tharini Sivasubramaniyam, Hassaan Maan, Aniqa B. Khan, Amina A. Abow, Stephanie A. Schroer, Sharon J. Hyduk, Marwan G. Althagafi, Trevor D. McKee, Fred Fu, Shiva Shabro, Antigona Ulndreaj, Felix Chiu, Elvira Paneda, Shaun Pacheco, Tao Wang, Angela Li, Jean X. Jiang, Peter Libby, Mansoor Husain, Bo Wang, Barry B. Rubin, Myron I. Cybulsky, Clinton S. Robbins
Journal: Immunity (2022)
Methylation risk scores for childhood aeroallergen sensitization: Results from the LISA birth cohort
Authors: Anna Kilanowski, Junyu Chen, Todd Everson, Elisabeth Thiering, Rory Wilson, Nicole Gladish, Melanie Waldenberger, Hongmei Zhang, Juan C. Celedón, Esteban G. Burchard, Annette Peters, Marie Standl, Anke Hüls
Journal: Allergy (2022)

Abstract Background Epigenomic (e.g., DNA methylation [DNAm]) changes have been hypothesized as intermediate step linking environmental exposures with allergic disease. Associations between individual DNAm at CpGs and allergic diseases have been reported, but their joint predictive capability is unknown. Methods Data were obtained from 240 children of the German LISA cohort. DNAm was measured in blood clots at 6 ( N = 234) and 10 years ( N = 227) using the Illumina EPIC chip. Presence of aeroallergen sensitization was measured in blood at 6, 10, and 15 years. We calculated six methylation risk scores (MRS) for allergy‐related phenotypes, like total and specific IgE, asthma, or any allergies, based on available publications and assessed their performances both cross‐sectionally (biomarker) and prospectively (predictor of the disease). Dose–response associations between aeroallergen sensitization and MRS were evaluated. Results All six allergy‐related MRS were highly correlated ( r &gt; .86), and seven CpGs were included in more than one MRS. Cross‐sectionally, we observed an 81% increased risk for aeroallergen sensitization at 6 years with an increased MRS by one standard deviation (best‐performing MRS, 95% confidence interval = [43%; 227%]). Significant associations were also seen cross‐sectionally at 10 years and prospectively, though the effect of the latter was attenuated when restricted to participants not sensitized at baseline. A clear dose–response relationship with levels of aeroallergen sensitization could be established cross‐sectionally, but not prospectively. Conclusion We found good classification and prediction capabilities of calculated allergy‐related MRS cross‐sectionally, underlining the relevance of altered gene‐regulation in allergic diseases and providing insights into potential DNAm biomarkers of aeroallergen sensitization.
Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies
Authors: Gita Thanarajasingam, Lori M Minasian, Vishal Bhatnagar, Franco Cavalli, R Angelo De Claro, Amylou C Dueck, Tarec C El-Galaly, Neil Everest, Jan Geissler, Christian Gisselbrecht, Nicole Gormley, John Gribben, Mary Horowitz, S Percy Ivy, Caron A Jacobson, Armand Keating, Paul G Kluetz, Yok Lam Kwong, Richard F Little, Matthew J Matasar, Maria-Victoria Mateos, Kristen McCullough, Robert S Miller, Mohamad Mohty, Philippe Moreau, Lindsay M Morton, Sumimasa Nagai, Abhilasha Nair, Loretta Nastoupil, Kaye Robertson, Surbhi Sidana, Karin E Smedby, Pieter Sonneveld, Kyriaki Tzogani, Flora E van Leeuwen, Galina Velikova, Diego Villa, John R Wingard, John F Seymour, Thomas M Habermann
Journal: The Lancet Haematology (2022)
Evaluation of Bronchiolitis-Related Emergency Department Visits From 2004 to 2018
Authors: Justin Brunet, Peter J. Gill, Haris Imsirovic, Patricia C. Parkin, Teresa To, Suzanne Schuh, Sanjay Mahant
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
Association of Food and Nonalcoholic Beverage Marketing With Children and Adolescents’ Eating Behaviors and Health
Authors: Emma Boyland, Lauren McGale, Michelle Maden, Juliet Hounsome, Angela Boland, Kathryn Angus, Andrew Jones
Journal: JAMA Pediatrics (2022)

<h3>Importance</h3> There is widespread interest in the effect of food marketing on children; however, the comprehensive global evidence reviews are now dated. <h3>Objective</h3> To quantify the association of food and nonalcoholic beverage marketing with behavioral and health outcomes in children and adolescents to inform updated World Health Organization guidelines. <h3>Data Sources</h3> Twenty-two databases were searched (including MEDLINE, CINAHL, Web of Science, Embase, and The Cochrane Library) with a publication date limit from January 2009 through March 2020. <h3>Study Selection</h3> Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Inclusion criteria were primary studies assessing the association of food marketing with specified outcomes in children and adolescents (aged 0-19 years). Exclusion criteria were qualitative studies or those on advertising of infant formula. Of 31 063 articles identified, 96 articles were eligible for inclusion in the systematic review, and 80 articles in the meta-analysis (19 372 participants). <h3>Data Extraction and Synthesis</h3> Two reviewers independently extracted data. Random-effects models were used for meta-analyses; meta-regressions, sensitivity analyses, and<i>P</i>curve analyses were also performed. Where appropriate, pooling was conducted using combining<i>P</i>values and vote counting by direction of effect. Grading of Recommendations Assessment, Development, and Evaluation was used to judge certainty of evidence. <h3>Main Outcomes and Measures</h3> Critical outcomes were intake, choice, preference, and purchasing. Important outcomes were purchase requests, dental caries, body weight, and diet-related noncommunicable diseases. <h3>Results</h3> Participants totaled 19 372 from 80 included articles. Food marketing was associated with significant increases in intake (standardized mean difference [SMD], 0.25; 95% CI, 0.15-0.35;<i>P</i> &lt; .001), choice (odds ratio, 1.77; 95% CI, 1.26-2.50;<i>P</i> &lt; .001), and preference (SMD, 0.30; 95% CI, 0.12-0.49;<i>P</i> = .001). Substantial heterogeneity (all &gt;76%) was unexplained by sensitivity or moderator analyses. The combination of<i>P</i>values for purchase requests was significant but no clear evidence was found for an association of marketing with purchasing. Data on dental health and body weight outcomes were scarce. The certainty of evidence was graded as very low to moderate for intake and choice, and very low for preference and purchasing. <h3>Conclusions and Relevance</h3> In this systematic review and meta-analysis, food marketing was associated with increased intake, choice, preference, and purchase requests in children and adolescents. Implementation of policies to restrict children’s exposure is expected to benefit child health.
Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by <i>NRG1</i> Gene Rearrangements
Authors: Alison M. Schram, Igor Odintsov, Madelyn Espinosa-Cotton, Inna Khodos, Whitney J. Sisso, Marissa S. Mattar, Allan J.W. Lui, Morana Vojnic, Sara H. Shameem, Thrusha Chauhan, Jean Torrisi, Jim Ford, Marie N. O'Connor, Cecile A.W. Geuijen, Ron C.J. Schackmann, Jeroen J. Lammerts van Bueren, Ernesto Wasserman, Elisa de Stanchina, Eileen M. O'Reilly, Marc Ladanyi, Alexander Drilon, Romel Somwar
Journal: Cancer Discovery (2022)

Abstract NRG1 rearrangements are recurrent oncogenic drivers in solid tumors. NRG1 binds to HER3, leading to heterodimerization with other HER/ERBB kinases, increased downstream signaling, and tumorigenesis. Targeting ERBBs, therefore, represents a therapeutic strategy for these cancers. We investigated zenocutuzumab (Zeno; MCLA-128), an antibody-dependent cellular cytotoxicity–enhanced anti-HER2xHER3 bispecific antibody, in NRG1 fusion–positive isogenic and patient-derived cell lines and xenograft models. Zeno inhibited HER3 and AKT phosphorylation, induced expression of apoptosis markers, and inhibited growth. Three patients with chemotherapy-resistant NRG1 fusion–positive metastatic cancer were treated with Zeno. Two patients with ATP1B1–NRG1–positive pancreatic cancer achieved rapid symptomatic, biomarker, and radiographic responses and remained on treatment for over 12 months. A patient with CD74–NRG1-positive non–small cell lung cancer who had progressed on six prior lines of systemic therapy, including afatinib, responded rapidly to treatment with a partial response. Targeting HER2 and HER3 simultaneously with Zeno is a novel therapeutic paradigm for patients with NRG1 fusion–positive cancers. Significance: NRG1 rearrangements encode chimeric ligands that activate the ERBB receptor tyrosine kinase family. Here we show that targeting HER2 and HER3 simultaneously with the bispecific antibody Zeno leads to durable clinical responses in patients with NRG1 fusion–positive cancers and is thus an effective therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1171
Promoting antigen escape from dendritic cell endosomes potentiates anti-tumoral immunity
Authors: Jean-Pierre Bikorimana, Natasha Salame, Simon Beaudoin, Mohammad Balood, Théo Crosson, Jamilah Abusarah, Sebastien Talbot, Raimar Löbenberg, Sebastien Plouffe, Moutih Rafei
Journal: Cell Reports Medicine (2022)

The cross-presenting capacity of dendritic cells (DCs) can be limited by non-specific degradation during endosome maturation. To bypass this limitation, we present in this study a new Accum-based formulation designed to promote endosome-to-cytosol escape. Treatment of primary DCs with Accum linked to the xenoantigen ovalbumin (OVA) triggers endosomal damages and enhances protein processing. Despite multiple challenges using ascending doses of tumor cells, DC prophylactic vaccination results in complete protection due to increased levels of effector CD4 and CD8 T cells as well as high production of pro-inflammatory mediators. When combined with anti-PD-1, therapeutic vaccination using both syngeneic and allogeneic Accum-OVA-pulsed DCs triggers potent anti-tumoral responses. The net outcome culminates in increased CD11c, CD8, and NK infiltration along with a high CD8/Treg ratio. These highly favorable therapeutic effects highlight the promising potential of Accum as a distinct and potent technology platform suitable for the design of next generation cell cancer vaccines.
Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment
Authors: Cuidi Li, Changwei Li, Zhenjiang Ma, Hongfang Chen, Huitong Ruan, Lianfu Deng, Jinwu Wang, Wenguo Cui
Journal: Bioactive Materials (2022)

The 3D printing technique is suitable for patient-specific implant preparation for bone repair after bone tumor resection. However, improving the survival rate due to tumor recurrence remains a challenge for implants. The macrophage polarization induction to M2-type tumor-associated macrophages (TAMs) by the tumor microenvironment is a key factor of immunosuppression and tumor recurrence. In this study, a regenerative scaffold regulating the macrophage immune microenvironment and promoting bone regeneration in a dual-stage process for the postoperative treatment of bone tumors was constructed by binding a colony-stimulating factor 1 receptor (CSF-1R) inhibitor GW2580 onto in situ cosslinked hydroxybutylchitosan (HBC)/oxidized chondroitin sulfate (OCS) hydrogel layer covering a 3D printed calcium phosphate scaffold based on electrostatic interaction. The hydrogel layer on scaffold surface not only supplied abundant sulfonic acid groups for stable loading of the inhibitor, but also acted as the cover mask protecting the bone repair part from exposure to unhealthy growth factors in the microenvironment at the early treatment stage. With local prolonged release of inhibitor being realized via the functional material design, CSF-1R, the main pathway that induces polarization of TAMs, can be efficiently blocked, thus regulating the immunosuppressive microenvironment and inhibiting tumor development at a low therapeutic dose. At the later stage of treatment, calcium phosphate component of the scaffold can facilitate the repair of bone defects caused by tumor excision. In conclusion, the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment.
Associations of Serum Carotenoids With Risk of Cardiovascular Mortality Among Individuals With Type 2 Diabetes: Results From NHANES
Authors: Zixin Qiu, Xue Chen, Tingting Geng, Zhenzhen Wan, Qi Lu, Lin Li, Kai Zhu, Xuena Zhang, Yujie Liu, Xiaoyu Lin, Liangkai Chen, Zhilei Shan, Liegang Liu, An Pan, Gang Liu
Journal: Diabetes Care (2022)

OBJECTIVE Although carotenoids have been suggested to exhibit antioxidant properties, some experimental studies reported that β-carotene may show pro-oxidant effects under certain conditions. Current evidence regarding the cardiovascular effects of carotenoids among patients with type 2 diabetes (T2D) is scarce. This study aimed to prospectively examine the associations of individual serum carotenoid concentrations with cardiovascular mortality among adults with T2D. RESEARCH DESIGN AND METHODS This analysis included 3,107 individuals with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001–2006. Cardiovascular mortality was ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After multivariate adjustment including lifestyles, dietary factors, glucose control, and other major carotenoids, higher serum β-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner. When extreme quartiles of β-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (Ptrend = 0.002); and per one-unit increment in natural log-transformed serum β-carotene was associated with a 46% higher risk of cardiovascular mortality (P = 0.001). Other individual carotenoids (α-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin) were not significantly associated with the risk of cardiovascular mortality. Consistent results were observed when stratifying by age, sex, race, BMI, smoking status, diabetes duration, and glycated hemoglobin A1c levels. CONCLUSIONS Higher concentrations of serum β-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D. Our findings, if replicated, underscore the need to estimate the optimal serum β-carotene concentrations in individuals with T2D.
Outcome predictors in SARS-CoV-2 disease (COVID-19): The prominent role of IL-6 levels and an IL-6 gene polymorphism in a western Sicilian population
Authors: Lydia Giannitrapani, Giuseppa Augello, Luigi Mirarchi, Simona Amodeo, Nicola Veronese, Bruna Lo Sasso, Rosaria Vincenza Giglio, Anna Licata, Mario Barbagallo, Marcello Ciaccio, Melchiorre Cervello, Maurizio Soresi
Journal: Journal of Infection (2022)
Efficacy, safety, and immunogenicity of an inactivated, adjuvanted enterovirus 71 vaccine in infants and children: a multiregion, double-blind, randomised, placebo-controlled, phase 3 trial
Authors: Trong Toan Nguyen, Cheng-Hsun Chiu, Chien-Yu Lin, Nan-Chang Chiu, Po-Yen Chen, Thi Tuong Vy Le, Dang Ngan Le, An Han Duong, Van Luan Nguyen, Thi Nguyet Huynh, Huu Khanh Truong, Trong Lan Phan, Thi Thanh Thao Nguyen, Shin-Ru Shih, Chung‑Guei Huang, Yi-Jen Weng, Erh-Fang Hsieh, Stanley Chang, Charles Chen, I-Chen Tai, Li-Min Huang
Journal: The Lancet (2022)
The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure
Authors: Olivier Boucherat, Vineet Agrawal, Allan Lawrie, Sebastien Bonnet
Journal: Circulation Research (2022)

Pulmonary hypertension (PH) describes heterogeneous population of patients with a mean pulmonary arterial pressure &gt;20 mm Hg. Rarely, PH presents as a primary disorder but is more commonly part of a complex phenotype associated with comorbidities. Regardless of the cause, PH reduces life expectancy and impacts quality of life. The current clinical classification divides PH into 1 of 5 diagnostic groups to assign treatment. There are currently no pharmacological cures for any form of PH. Animal models are essential to help decipher the molecular mechanisms underlying the disease, to assign genotype-phenotype relationships to help identify new therapeutic targets, and for clinical translation to assess the mechanism of action and putative efficacy of new therapies. However, limitations inherent of all animal models of disease limit the ability of any single model to fully recapitulate complex human disease. Within the PH community, we are often critical of animal models due to the perceived low success upon clinical translation of new drugs. In this review, we describe the characteristics, advantages, and disadvantages of existing animal models developed to gain insight into the molecular and pathological mechanisms and test new therapeutics, focusing on adult forms of PH from groups 1 to 3. We also discuss areas of improvement for animal models with approaches combining several hits to better reflect the clinical situation and elevate their translational value.
First Amphetamine Transdermal Patch Approved for ADHD
Authors: Howard D. Larkin
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
Targeted Analysis of Cell-free Circulating Tumor DNA is Suitable for Early Relapse and Actionable Target Detection in Patients with Neuroblastoma
Authors: Marco Lodrini, Josefine Graef, Theresa M. Thole-Kliesch, Kathy Astrahantseff, Annika Sprüssel, Maddalena Grimaldi, Constantin Peitz, Rasmus B. Linke, Jan F. Hollander, Erwin Lankes, Annette Künkele, Lena Oevermann, Georg Schwabe, Jörg Fuchs, Annabell Szymansky, Johannes H. Schulte, Patrick Hundsdörfer, Cornelia Eckert, Holger Amthauer, Angelika Eggert, Hedwig E. Deubzer
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Treating refractory or relapsed neuroblastoma remains challenging. Monitoring body fluids for tumor-derived molecular information indicating minimal residual disease supports more frequent diagnostic surveillance and may have the power to detect resistant subclones before they give rise to relapses. If actionable targets are identified from liquid biopsies, targeted treatment options can be considered earlier. Experimental Design: Droplet digital PCR assays assessing MYCN and ALK copy numbers and allelic frequencies of ALK p.F1174L and ALK p.R1275Q mutations were applied to longitudinally collected liquid biopsies and matched tumor tissue samples from 31 patients with high-risk neuroblastoma. Total cell-free DNA (cfDNA) levels and marker detection were compared with data from routine clinical diagnostics. Results: Total cfDNA concentrations in blood plasma from patients with high-risk neuroblastoma were higher than in healthy controls and consistently correlated with neuron-specific enolase levels and lactate dehydrogenase activity but not with 123I-meta-iodobenzylguanidine scores at relapse diagnosis. Targeted cfDNA diagnostics proved superior for early relapse detection to all current diagnostics in 2 patients. Marker analysis in cfDNA indicated intratumor heterogeneity for cell clones harboring MYCN amplifications and druggable ALK alterations that were not detectable in matched tumor tissue samples in 17 patients from our cohort. Proof of concept is provided for molecular target detection in cerebrospinal fluid from patients with isolated central nervous system relapses. Conclusions: Tumor-specific alterations can be identified and monitored during disease course in liquid biopsies from pediatric patients with high-risk neuroblastoma. This approach to cfDNA surveillance warrants further prospective validation and exploitation for diagnostic purposes and to guide therapeutic decisions.
Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes
Authors: Taylor Fuselier, Paula Mota de Sa, M.M. Fahd Qadir, Beibei Xu, Camille Allard, Mathew M. Meyers, Joseph P. Tiano, Bin S. Yang, Vasily Gelfanov, Sarah H. Lindsey, Richard D. Dimarchi, Franck Mauvais-Jarvis
Journal: Cell Reports Medicine (2022)

We study the efficacy of a glucagon-like peptide-1 (GLP-1) and estrogen dual agonist (GLP1-E2) in pancreatic islet protection. GLP1-E2 provides superior protection from insulin-deficient diabetes induced by multiple low-dose streptozotocin (MLD-STZ-diabetes) and by the Akita mutation in mice than a GLP-1 monoagonist. GLP1-E2 does not protect from MLD-STZ-diabetes in estrogen receptor-α (ERα)-deficient mice and fails to prevent diabetes in Akita mice following GLP-1 receptor (GLP-1R) antagonism, demonstrating the requirement of GLP-1R and ERα for GLP1-E2 antidiabetic actions. In the MIN6 β cell model, GLP1-E2 activates estrogen action following clathrin-dependent, GLP-1R-mediated internalization and lysosomal acidification. In cultured human islet, proteomic bioinformatic analysis reveals that GLP1-E2 amplifies the antiapoptotic pathways activated by monoagonists. However, in cultured mouse islets, GLP1-E2 provides antiapoptotic protection similar to monoagonists. Thus, GLP1-E2 promotes GLP-1 and E2 antiapoptotic signals in cultured islets, but in vivo, additional GLP1-E2 actions in non-islet cells expressing GLP-1R are instrumental to prevent diabetes.