tbuckley/cabot-search huggingface dataset:
Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages
Authors: C. C. Bain, D. A. Gibson, N. J. Steers, K. Boufea, P. A. Louwe, C. Doherty, V. González-Huici, R. Gentek, M. Magalhaes-Pinto, T. Shaw, M. Bajénoff, C. Bénézech, S. R. Walmsley, D. H. Dockrell, P. T. K. Saunders, N. N. Batada, S. J. Jenkins
Journal: Science Immunology (2020)

Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis, and metastatic cancer; thus, understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover, and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single-cell RNA sequencing revealed marked dimorphisms in gene expression between male and female peritoneal macrophages that was, in part, explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic
Understanding bone fragility: theoretical explanation to non-physician health professionals
Authors: Toshihiro Sugiyama
Journal: Annals of the Rheumatic Diseases (2020)

Understanding bone fragility: theoretical explanation to non-physician health professionalsThe European League Against Rheumatism recently established timely and highly important recommendation for non-physician health professionals regarding the prevention and management of bone fractures among older adults. 1 To support the health professionals' understanding of skeletal fragility, I would like to provide a theoretical explanation. 2 3 First, non-physician health professionals are expected to play a role in the improvement of patient adherence to pharmacotherapy for osteoporosis. 1Here, it should be paid attention that the effects of osteoporosis drugs except bisphosphonates with mineral binding capacity are lost rapidly after discontinuation, 4 which can be reasonably explained by functional adaptation of bone to mechanical loading during physical activity. 3Second, the homeostatic system in the skeleton 2 can also explain why the small and transient effect of calcium supplementation on areal bone mineral density, measured by dual-energy X-ray absorptiometry, is lost after discontinuation. 5Finally, although vigorousintensity exercise would improve bone fragility, 6 the effect can be similarly lost after discontinuation, resulting from the skeletal adaptation to mechanical environment. 7Long-term continuation of exercise should be therefore given priority over the intensity; for example, rapid bone loss following stroke 8 indicates the significance of even light-intensity physical activity.
Abstract 9874: Bleeding Risk Associated With Thromboprophylaxis Combination Therapy is Low for Patients With Coronary Artery Aneurysms After Kawasaki Disease
Authors: Tisiana Low, Anusha Jegatheeswaran, Paul J Devlin, Nita Chahal, Leonardo Brandao, Brian W McCrindle
Journal: Circulation (2019)

Background: Kawasaki disease (KD) may lead to coronary artery aneurysms (CAA) with risk of thrombosis, precipitating acute CV events. We aimed to determine the bleeding risk in patients with KD and...
Institutionalisation and deinstitutionalisation of children 2: policy and practice recommendations for global, national, and local actors
Authors: Philip S Goldman, Marian J Bakermans-Kranenburg, Beth Bradford, Alex Christopoulos, Patricia Lim Ah Ken, Christopher Cuthbert, Robbie Duchinsky, Nathan A Fox, Stela Grigoras, Megan R Gunnar, Rawan W Ibrahim, Dana Johnson, Santi Kusumaningrum, Ni Luh Putu Maitra Agastya, Frederick M Mwangangi, Charles A Nelson, Ellie M Ott, Sophie Reijman, Marinus H van IJzendoorn, Charles H Zeanah, Yuning Zhang, Edmund J S Sonuga-Barke
Journal: The Lancet Child & Adolescent Health (2020)

Worldwide, millions of children live in institutions, which runs counter to both the UN-recognised right of children to be raised in a family environment, and the findings of our accompanying systematic review of the physical, neurobiological, psychological, and mental health costs of institutionalisation and the benefits of deinstitutionalisation of child welfare systems. In this part of the Commission, international experts in reforming care for children identified evidence-based policy recommendations to promote family-based alternatives to institutionalisation. Family-based care refers to caregiving by extended family or foster, kafalah (the practice of guardianship of orphaned children in Islam), or adoptive family, preferably in close physical proximity to the biological family to facilitate the continued contact of children with important individuals in their life when this is in their best interest. 14 key recommendations are addressed to multinational agencies, national governments, local authorities, and institutions. These recommendations prioritise the role of families in the lives of children to prevent child separation and to strengthen families, to protect children without parental care by providing high-quality family-based alternatives, and to strengthen systems for the protection and care of separated children. Momentum for a shift from institutional to family-based care is growing internationally—our recommendations provide a template for further action and criteria against which progress can be assessed.
Pitfalls in the Detection of Insulinomas With Glucagon-Like Peptide-1 Receptor Imaging
Authors: Kwadwo Antwi, Matthias Hepprich, Natasha A. Müller, Jean Claude Reubi, Melpomeni Fani, Christof Rottenburger, Guillaume Nicolas, Felix Kaul, Emanuel R. Christ, Damian Wild
Journal: Clinical Nuclear Medicine (2020)

Purpose Physiological pancreaticoduodenal uptake of radiolabeled exendin-4 in Brunner glands of the proximal duodenum is the most common pitfall for false interpretation of glucagon-like peptide-1 receptor (GLP-1R) imaging. The aim of this study was to analyze the pancreaticoduodenal uptake in GLP-1R PET/CT and SPECT/CT images and to identify additional potential reading pitfalls in patients with suspected insulinoma. Methods A post hoc analysis of a prospective study, including 52 consecutive patients, was performed. All patients underwent 1 68 Ga-exendin-4 PET/CT and 2 111 In-exendin-4 SPECT/CT scans (4 and 72 hours postinjection) in a randomized crossover order. Three board-certified nuclear medicine physicians read all scans independently. They were unaware of other results. Reference standard was surgery with histopathological confirmation of an insulinoma/nesidioblastosis and normalization of blood glucose levels after surgery. Results There were no false-positive readings. However, there were a number of false-negative PET/CT and SPECT/CT readings, respectively: (1) due to false interpretation of uptake in the pancreaticoduodenal region (falsely interpreted as physiological uptake in Brunner glands instead of an insulinoma in 0.6% vs 9.0%), (2) due to ectopic insulinoma (0% vs 2.6%), (3) due to small insulinoma (1.9% vs 5.1%), (4) due to insulinoma overlap with kidneys (1.9% vs 4.5%), and (5) due to nesidioblastosis (0.6% and 1.9%). Pitfalls were identified in all GLP-1R PET/CT and SPECT/CT scans. Conclusions Peripancreatic uptake, small size of an insulinoma, insulinoma overlap with kidneys, and presence of nesidioblastosis are potential pitfalls in GLP-1R imaging, which can lead to false reading results.
Audio Interview: A Look at SARS-CoV-2 Transmission
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

A Look at SARS-CoV-2 Transmission In this audio interview conducted on June 17, 2020, the editors discuss the transmission of SARS-CoV-2, the causative agent of Covid-19, looking at new evidence fr...
Perspectives on Cannabis Research—Barriers and Recommendations
Authors: Margaret Haney
Journal: JAMA Psychiatry (2020)

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 Psychiatry 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 Psychiatry journal
Electronic cigarettes and vaping associated pulmonary illness (VAPI): A narrative review
Authors: R. Hage, V. Fretz, M.M. Schuurmans
Journal: Pulmonology (2020)

Electronic (e-) cigarettes are used to heat liquids producing aerosols for inhalation. Recently there have been reports of a large number of adverse outcomes relating to e-cigarette consumption (vaping), which has been referred to as "vaping associated pulmonary illness" (VAPI). This review provides an overview of clinical, radiological and pathological features of VAPI in the literature. We also describe a case of VAPI, presenting with symptoms of bronchiolitis, responding well to azithromycin in addition to the usual treatments provided for such cases. We searched original papers, observational studies, case reports, and meta-analyses published between 2000 and 2019 in English in PubMed database using the keywords: e-cigarette, "vaping associated pulmonary illness", VAPI, EVALI, vaping AND "lung injury". We also used data of the Centers of Disease Control (CDC) website. From an initial search of PubMed, 62 potential articles were identified, and another 9 studies were identified from the bibliographies of retrieved articles. In this search we found 7 case series and 16 case reports, which were included in the review. In this search we also found 4 review articles. VAPI is a syndrome presenting with isolated pulmonary or combined pulmonary, gastrointestinal and constitutional symptoms and can be rapidly progressive, leading to respiratory failure, often requiring invasive respiratory support. There is an urgent need for more research on VAPI especially relating to etiology, treatment and prevention.
SAT0266 FAMILIAR AGGREGATION OF LONGEVITY IN GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA
Authors: M. Milchert, M. Brzosko
Journal: Annals of the Rheumatic Diseases (2020)

Background: The long-term mortality in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is unexpectedly decreased (1,2,3,4) or at least not increased regardless increased mortality risk factors that these diseases share with other systemic inflammatory disorders. Objectives: We aimed to test the hypothesis on aggregation of increased longevity in families of PMR/GCA patients because the family members of long-lived subjects have a survival advantage. Methods: After questioning our patients we compared age of death of 358 parents of 179 PMR and GCA patients with corresponding data retrieved from 506 parents of 235 randomly collected age and sex matched controls. Results: We found the number of nonagenarian (≥90 year old) mothers of PMR/GCA patients significantly higher vs controls. Both nonagenarian parents were found in 6 patients (3.35%) and in none of the controls. Decreased number of nonagenarian fathers of our patients remains unexplained. Table 1. Number of nonagenarians (.90 years olds) in parents of PMR/GCA patients Parents age PMR/GCA (N=179) Controls (N=253) OR 95%CI p Mothers &lt;90 148 (82.68%) 243 (96.05%) ≥90 31 (17.32%) 10 (3.95%) 2.34 1.11-11.95 &lt;0.0005 Fathers &lt;90 ≥90 161 (89.94%) 18 (10.06%) 203 (80.24%) 50 (19.76%) 0.45 0.24-0.83 0.0064 One of parents &lt;90 ≥90 136 (75.98%) 43 (24.02%) 193 (76.28%) 60 (23.72%) 1.02 0.63-1.63 0.9412 Both parents &lt;90 ≥90 173 (96.65%) 6 (3.35%) 253 (100.00%) 0 (0%) 8.77 2.26-405.10 0.003 Mothers of female patients &lt;90 ≥90 105 (84%) 20 (16%) 149 (97%) 4 (3%) 7.1 2.27-29.19 0.0001 Mothers of male patients &lt;90 ≥90 43 (80) 11 (20%) 94 (94%) 6 (6%) 4.01 1.25-13.97 0.0066 N - number of all parents Conclusion: Confirming our findings in a wider studies would imply a need of including some genetic or behavioural factors to explain PMR/GCA survival advantage. References: [1]Garen T, Lerang K, Hoffmann-Vold AM, et al. Mortality and causes of death across the systemic connective tissue diseases and the primary systemic vasculitides. Rheumatology (Oxford) 2019;58:313-20. [2]Bengtsson BA, Malmvall BE. Prognosis of giant cell arteritis including temporal arteritis and polymyalgia rheumatica. A follow-up study on ninety patients treated with corticosteroids. Acta Med Scand 1981;209:337-45. [3]Andersson R, Malmvall BE, Bengtsson BA. Long-term survival in giant cell arteritis including temporal arteritis and polymyalgia rheumatica. A follow-up study of 90 patients treated with corticosteroids. Acta Med Scand 1986;220:361-4. [4]Gonzalez-Gay MA, Blanco R, Abraira V et al Giant cell arteritis in Lugo, Spain, is associated with low longterm mortality. J Rheumatol 1997;24:21716. Acknowledgments: o professor Maciej Markiewski for revision of the manuscript Disclosure of Interests: Marcin Milchert Consultant of: Sanofi, Roche, Marek Brzosko: None declared
Aptamers against mouse and human tumor-infiltrating myeloid cells as reagents for targeted chemotherapy
Authors: Adriana De La Fuente, Serena Zilio, Jimmy Caroli, Dimitri Van Simaeys, Emilia M. C. Mazza, Tan A. Ince, Vincenzo Bronte, Silvio Bicciato, Donald T. Weed, Paolo Serafini
Journal: Science Translational Medicine (2020)

Local delivery of anticancer agents has the potential to maximize treatment efficacy and minimize the acute and long-term systemic toxicities. Here, we used unsupervised systematic evolution of ligands by exponential enrichment to identify four RNA aptamers that specifically recognized mouse and human myeloid cells infiltrating tumors but not their peripheral or circulating counterparts in multiple mouse models and from patients with head and neck squamous cell carcinoma (HNSCC). The use of these aptamers conjugated to doxorubicin enhanced the accumulation and bystander release of the chemotherapeutic drug in both primary and metastatic tumor sites in breast and fibrosarcoma mouse models. In the 4T1 mammary carcinoma model, these doxorubicin-conjugated aptamers outperformed Doxil, the first clinically approved highly optimized nanoparticle for targeted chemotherapy, promoting tumor regression after just three administrations with no detected changes in weight loss or blood chemistry. These RNA aptamers recognized tumor infiltrating myeloid cells in a variety of mouse tumors in vivo and from human HNSCC ex vivo. This work suggests the use of RNA aptamers for the detection of myeloid-derived suppressor cells in humans and for a targeted delivery of chemotherapy to the tumor microenvironment in multiple malignancies.
Updated Antitumor Activity of Crizotinib in Patients with MET Exon 14-Altered Advanced Non-Small Cell Lung Cancer
Authors: A Drilon, J Clark, J Weiss, S Ou, Camidge, B Solomon, G Otterson, L Villaruz, G Riely, R Heist, G Shapiro, D Murphy, S Wang, T Usari, S Li, K Wilner, P Paik
Journal: Journal of Thoracic Oncology (2018)
Association of Exercise Intolerance With Emotional Distress, Attainment of Social Roles, and Health-Related Quality of Life Among Adult Survivors of Childhood Cancer
Authors: Samah Hayek, Tara M. Brinkman, Juan C. Plana, Vijaya M. Joshi, Russell V. Leupker, Jean B. Durand, Daniel M. Green, Robyn E. Partin, Aimee K. Santucci, Rebecca M. Howell, Deo Kumar Srivastava, Melissa M. Hudson, Leslie L. Robison, Gregory T. Armstrong, Kirsten K. Ness
Journal: JAMA Oncology (2020)

Exercise intolerance is associated with increased risk for morbidity and mortality in childhood cancer survivors. However, an association between exercise intolerance and psychosocial outcomes has not been fully explored.
Isaiah J. (Josh) Fidler, DVM, PhD, FAACR: In Memoriam (1936–2020)—A Visionary Research Career Dedicated to Understanding the Complexities of Cancer Metastasis
Authors: George Poste
Journal: Cancer Research (2020)

</br>![][1]</img> In a time of pandemic distractions and anxieties, it is easy to succumb to the tyranny of the immediate. Then an event happens to jolt the senses and trigger a flood of memories and broader reflection on those rare individuals who truly make a difference in advancing science
Protein sumoylation with SUMO1 promoted by Pin1 in glioma stem cells augments glioblastoma malignancy
Authors: Aili Zhang, Weiwei Tao, Kui Zhai, Xiaoguang Fang, Zhi Huang, Jennifer S Yu, Andrew E Sloan, Jeremy N Rich, Wenchao Zhou, Shideng Bao
Journal: Neuro-Oncology (2020)

Abstract Background The tumorigenic potential of glioma stem cells (GSCs) is associated with multiple reversible molecular alternations, but the role of posttranslational protein sumoylation in GSCs has not been elucidated. The development of GSC-targeting drugs relies on the discovery of GSC-preferential molecular modifications and the relevant signaling pathways. In this work, we investigated the protein sumoylation status, the major sumoylated substrate, and the key regulatory enzyme in GSCs to explore the therapeutic potential of disrupting protein sumoylation for glioblastoma (GBM) treatment. Methods Patient-derived GSCs, primary GBM sections, and intracranial GBM xenografts were used to determine protein sumoylation and the related molecular mechanisms by immunoblot, quantitative PCR, immunoprecipitation, immunofluorescence, and immunohistochemistry. Orthotopic GBM xenograft models were applied to investigate the inhibition of tumor growth by disrupting protein sumoylation with short hairpin (sh)RNAs or molecular inhibitors. Results We show that high levels of small ubiquitin-related modifier 1 (SUMO1)—but not SUMO2/3—modified sumoylation are preferentially present in GSCs. The promyelocytic leukemia (PML) protein is a major SUMO1-sumoylated substrate in GSCs, whose sumoylation facilitates its interaction with c-Myc to stabilize c-Myc proteins. The prolyl-isomerase Pin1 is preferentially expressed in GSCs and functions as the key enzyme to promote SUMO1 sumoylation. Disruption of SUMO1 sumoylation by Pin1 silencing with shRNAs or inhibition with its inhibitor Juglone markedly abrogated GSC maintenance and mitigated GSC-driven tumor growth. Conclusions Our findings indicate that high SUMO1-modified protein sumoylation as a feature of GSCs is critical for GSC maintenance, suggesting that targeting SUMO1 sumoylation may effectively improve GBM treatment.
A phase III trial in progress comparing tislelizumab plus concurrent chemoradiotherapy (cCRT) with placebo plus cCRT in patients with localized esophageal squamous cell carcinoma (ESCC).
Authors: Wei-Hu Wang, Jiancheng Li, Tao Li, Kuaile Zhao, Rong Yu, Wenqing Wang, Mingqiu Chen, Long Liang, Jiyan Zou, Yidi Wang, Wei Shen, Zhe Wu, Zefen Xiao
Journal: Journal of Clinical Oncology (2020)

TPS475 Background: In China, esophageal cancer (EC) ranks as the eigth most common cancer and the sixth most common cause of cancer related death. The predominant histological subtype of EC is ESCC. At first diagnosis, more than half of patients (pts) with ESCC are unfit for surgery. An alternative to surgery is cCRT; however, many pts experience local failure or distant metastasis after cCRT. As such, innovative therapies are needed. Tislelizumab, an investigational humanized monoclonal antibody with high affinity and specificity for PD-1, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. In previous studies, tislelizumab, as a monotherapy and in combination with chemotherapy, was generally well tolerated and had antitumor activity in pts with ESCC. Methods: This phase 3, randomized, double-blind, placebo-controlled study (NCT03957590) is designed to compare the efficacy of tislelizumab versus placebo in combination with cCRT. Patients with histologically confirmed localized ESCC for whom cCRT is suitable and surgery is unsuitable/declined are being enrolled. Approximately 316 Chinese pts will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo (IV Q3W) in combination with cisplatin (25 mg/m 2 IV on Days 1-3 of each 3-week cycle) plus paclitaxel (135 mg/m 2 IV Q3W) and radiotherapy at a total dose of 50.4 Gy. An Independent Data Monitoring Committee will be established to assess the safety/tolerability of tislelizumab plus cCRT in the first 20 enrolled pts; monitoring across the study will occur at regular intervals thereafter. Progression-free survival (PFS), assessed by a Blinded Independent Review Committee per RECIST v1.1, is the primary endpoint. Secondary efficacy endpoints include overall response rate, duration of response, and overall survival. Incidence and severity of adverse events (CTCAE V5.0) and HRQoL are additional secondary endpoints. Exploratory endpoints include PFS rate at Years 1 and 2, pharmacokinetic profile, and predictive biomarker analyses. Clinical trial information: NCT03957590.