tbuckley/cabot-search huggingface dataset:
Abstract IA09: Immunotherapeutic approaches for pediatric solid tumors
Authors: Rupert Handgretinger
Journal: Cancer Research (2020)

Abstract For patients with primary metastatic or recurrent soft tissue sarcomas, cytotoxic chemotherapy is currently the primary treatment modality. Despite intensive chemotherapy, the outcome is poor and additional new therapeutic strategies in combination with chemotherapy have to be investigated. Immunotherapy, which involves the patient’s own or a new allogeneic immune system, might have great potential to improve the outcome of affected patients. We have focused on the use of haploidentical transplantation as a form of intensive immunotherapy in order to utilize a graft-versus-solid tumor effect, which might be exerted by donor-derived alloreactive Natural Killer (NK) cells, but also by donor-derived T cells. In a first pilot trial, we have transplanted 26 patients with relapsed neuroblastoma from a haploidentical donor. The transplant-related mortality (TRM) was 0% and the overall survival (OS) was 20%. We then started a protocol using haploidentical transplantation in 68 patients followed post-transplant by 6-9 cycles of the monoclonal anti-GD2 antibody ch14.18CHO. The TRM was 5% and the 3-year OS is 58%. In addition to neuroblastoma, we also hope to apply similar strategies to other pediatric advanced solid tumors including Ewing’s sarcoma, rhabdomyosarcoma, and others. We conclude that haploidentical transplantation of patients with relapsed/refractory solid tumors is a platform on which further immunotherapeutic strategies can be developed, such as antibodies directed against other targets than GD2, such as CD276, or bispecific T-cell engagers (BiTEs), chimeric antigen receptor (CAR) T-cells or CAR NK cells, or antibody/cytokine fusion proteins, and these approaches will be discussed. The main goal of immunotherapy, however, must be to establish a long-term memory immune response against the tumor, and haploidentical transplantation might facilitate such a response. Citation Format: Rupert Handgretinger. Immunotherapeutic approaches for pediatric solid tumors [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA09.
THU0268 NEURO-DEVELOPMENTAL OUTCOME IN CHILDREN BORN TO MOTHERS WITH SLE AND APS
Authors: M. Hassanien, E. Talaat, H. Abdellatif
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic Lupus erythematosus and antiphospholipid disease are very common autoimmune diseases in women at reproductive age. Objectives: Evaluate the neuro-developmental outcome in children born to mothers with SLE or APS and to assess and characterize memory impairment in children’s born to mother with systemic lupus erythematosus or APS using children’s memory scale and the relation between tetrahydrobiopterin concentration range of children with developmental and neurological disorders. Methods: Women attending rheumatology clinics University of Asyut, SLE patients were eligible if they met the American College of Rheumatology (ACR) criteria for SLE and APL prior to pregnancy, and had at least one live birth following SLE diagnosis. Maternal history Data collected using a structured format that included medical and obstetric history. A detailed history of medication exposures and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) during pregnancy was obtained. Offspring history Medical and developmental histories of the offspring including antenatal, delivery, prenatal and pediatric histories, as child’s cognitive, physical or social maturity compared with established age-appropriate norms. Speech or hearing delays, diagnosis of attention- deficit hyperactivity disorder (ADHD), or any special educational needs (eg, occupational or speech therapy, behavioral counseling) was recorded. Assessment and characterization of memory impairment using children’s memory scale by neurologists. Tetrahydrobiopterin was measured by ELISA compared to children born to control healthy subjects of the same age and sex. Results: Data on 38 mothers and 60 offspring were analysed: ADHD was reported for 15 of 60 (25%) offspring. Recent memory delay was detected in 93% (14/15) Speech delay 40% (6/15). Maternal APS history was significantly associated with increased use special educational need among offsprings, including after adjustment for lupus anticoagulant (LA) positivity (39.4% for delays age &gt;2 years; p&lt;0.05). Anticardiolipin and anti-BETA2GP1 were not detected to be associated with delays. Recent memory delay was associated with increased Tetrahydrobiopterin level (P=0.01). Conclusion: The prevalence of neurodevelopmental abnormalities in children born to mothers with SLE or APS seems to be higher than normal population and more educational attention is important in these children, and need long-term follow-up. Disclosure of Interests: None declared
Refractory esophagopleural fistula post-lobectomy successfully treated by endoscopic submucosal dissection and over-the-scope clip
Authors: Florian Béoletto, Florian Rostain, Adriane Lesne, Gaëtanne Roquet, Nada Nargues, Olivier Ragi, Mathieu Pioche
Journal: Endoscopy (2020)

Acquired esophagopleural fistulas are rare adverse events of pneumonectomy and occur in 0.2 to 1 % of cases [1].
Abstract #16: Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling
Authors: Hyun-Hee Lee, Sin-Aye Park, Eun-Hee Kim, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2009)

Piceatannol (3,4,3\#8217;,5\#8217;-tetrahydroxy-trans-stilbene), derived from the seeds of Euphorbia lagascae, has been reported to have anti-proliferative, anti-inflammatory, and anti-oxidant properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found that piceatannol treatment (30 \#956;M) significantly upregulated the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) and its mRNA transcript at 6 h and 3 h, respectively in human breast epithelial (MCF10A) cells. A redox-sensitive transcription factor NF-E2-related factor (Nrf2) plays a pivotal role in induced expression of many antioxidant and phase-2 detoxifying enzymes. Piceatannol induced translocation of Nrf2 into the nucleus and its transcriptional activities when treated to the MCF10A cells for 6 h. Up-regulation of HO-1 expression by piceatannol through direct binding of Nrf2 to antioxidant response element (ARE) was verified by the chromatin immunoprecipitation (ChIP) assay. siRNA knock down of Nrf2 gene abolished piceatannol-induced HO-1 expression. In addition, piceatannol-induced activation of Nrf2 was abrogated by the pharmacological inhibitor (LY294002) as well as the kinase dead form of Akt. HO-1 upregulation and Nrf2 activation induced by piceatannol were more prominent than those afforded by the same concentration of resveratrol (3,4\#8217;,5-trihydroxy-trans-stilbene) and oxyresveratrol (2,\#8217;,4,5\#8217;-tetrahydroxy-trans-stilbene), stilbene analogs structurally related to piceatannol. In an attempt to explain the cytoprotective or chemoprotective activity exerted by piceatannol, we examined its effect on the expression of HO-1 and the signaling pathways responsible for induction of this antioxidant enzyme. We hypothesize that an electrophilic quinone formed as a consequence of oxidation of piceatannol bearing the catechol moiety may bind covalently to Kelch-like ECH-associated protein 1 (Keap1), an inhibitory protein that sequesters Nrf2 in the cytoplasm. This will diminish the affinity of Keap1 for Nrf2. The thiol reducing agent dithiothreitol (100 \#956;M) attenuated piceatannol-induced Nrf2 activation and HO-1 expression. It is hence likely that piceatannol modifies specific cysteine residues of Keap1, which allows Nrf2 to translocate into the nucleus and bind to ARE, leading to enhancement of the expression of HO-1. The characteristic catechol moiety of piceatannol appears to be critical for the induction of Nrf2 activation and subsequent upregulation of HO-1.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 16.
Postexercise Ankle-Brachial Index Testing
Authors: Anurag Mehta, Laurence S. Sperling, Bryan J. Wells
Journal: JAMA (2020)

A 61-year-old woman with a history of hypertension presented for evaluation of exertional left calf discomfort. Her lower extremity systolic blood pressure and ankle-brachial index (ABI) measures declined after treadmill testing. What would you do next?
Pelvic Floor Therapy for Older Women With Urinary Incontinence—Can Group-Based Training Reduce the Population-Level Burden of This Condition?
Authors: Alison J. Huang
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Chronic Obstructive Pulmonary Disease
Authors: Wassim W. Labaki, Sharon R. Rosenberg
Journal: Annals of Internal Medicine (2020)

Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and progressive airflow obstruction. Tobacco smoking is the leading cause but not the only one. A postbronchodilator FEV1-FVC ratio less than 0.70 is required for a diagnosis of COPD. Inhaler therapy is the backbone of treatment and should be complemented by a multifaceted management strategy that includes counseling and pharmacotherapy for smoking cessation, pulmonary rehabilitation, treatment of comorbidities, administration of influenza and pneumococcal immunizations, and prescription of long-term oxygen therapy in hypoxemic patients.
Knowledge-primed neural networks enable biologically interpretable deep learning on single-cell sequencing data
Authors: Nikolaus Fortelny, Christoph Bock
Journal: Genome biology (2020)

Deep learning has emerged as a versatile approach for predicting complex biological phenomena. However, its utility for biological discovery has so far been limited, given that generic deep neural networks provide little insight into the biological mechanisms that underlie a successful prediction. Here we demonstrate deep learning on biological networks, where every node has a molecular equivalent, such as a protein or gene, and every edge has a mechanistic interpretation, such as a regulatory interaction along a signaling pathway.
In vitro and in vivo anti-tumor action of the S-adenosylmethionine decarboxylase (SAMDC) inhibitor SAM486A in human breast cancer cells: Effect on tumor polyamine (PA) and cell signaling
Authors: Xin Hu, Sharlene Washington, Michael F. Verderame, Laurence M. Demers, Andrea Manni
Journal: Cancer Research (2004)

5208  Current evidence indicates that increased cellular contents of PA (putrescine [Pu], spermidine [Sd] and spermine [Sm]) may contribute to breast cancer development and progression. Therefore, inhibition of PA synthesis represents a potential approach to breast cancer treatment and prevention. Both ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the PA pathway promoting the synthesis of Pu, and SAMDC involved in the synthesis of the more distal PA, Sd and Sm, are attractive therapeutic targets. In these experiments, we tested the biological and biochemical effects of the SAMDC inhibitor SAM486A (CGP 48664) in the hormone-independent MDA-MB 435 human breast cancer cell line. We observed that SAM486A inhibited the growth in liquid culture of MDA-MB 435 cells in a dose-dependent manner with an IC50 of 1uM. Its antiproliferative effect was associated with a consistent suppression of cellular Sm, a dose dependent increase in Pu (as a result of the compensatory increase in ODC) and a bell shaped dose-related increase in Sd. Combined inhibition of ODC with α-difluoromethylornithine (DFMO) and SAMDC with SAM486A, showed an enhanced antiproliferative activity compared to the individual treatments used at submaximal concentrations. While the effect of DFMO was totally rescued by exogenous Sd and Sm, the reversal of the SAM486A by these PA was considerably more modest. SAM486A treatment significantly reduced in a dose related fashion clonogenicity in soft agar and invasiveness in matrigel of MDA-MB 435 cells. Similarly to DFMO, SAM486A treatment increased ERK phosphorylation. This effect may be involved in its anti-tumor action since, in other experiments, we have observed that the anti-invasive effect of DFMO could be reversed by ERK inhibitor, PD 184352. SAM486A (but not DFMO) inhibited Serine 727 phosphorylation of STAT3. “In vivo” daily i.p. administration for 28 days of escalating doses of SAM486A (0, 1, 5, 10 mg/kg) to nude mice carrying orthotopically implanted MDA-MB 435 cells xenografts was well tolerated without any weight loss. The lowest dose tested (1mg/kg) exhibited the greatest anti-tumor action associated with significant suppression of cellular Sd and Sm. These results indicate that SAM486A has significant anti-tumor effects against human breast cancer cells “in vitro” and “in vivo”. Its combined use with DFMO offers promise for a superior anti-tumor action, since the two drugs may have complementary effects on PA synthesis and cellular signaling.
Abstract 10117: Basal Left Ventricle Longitudinal Strain Predicts Survival After Surgical Ventricular Repair
Authors: Olena Nemchyna, Natalia Solowjowa, Michael Dandel, Yuriy Hrytsyna, Julia Stein, Sajjad Soltani, Jan Knierim, Felix Schönrath, Volkmar Falk, Christoph Knosalla
Journal: Circulation (2019)

Introduction: Surgical ventricular repair (SVR) in pts with ischemic cardiomyopathy is aimed to enhance left ventricular (LV) performance and prevent progression of its pathological remodeling. The...
Closure of residual fistula after esophageal atresia repair in a 5-year-old using endoscopic submucosal dissection of surrounding mucosa
Authors: Grégoire Lavaud, Sophie Heissat, Auxane Chauveau, Noël Peretti, Alain Lachaux, Borathchakra Oung, Mathieu Pioche
Journal: Endoscopy (2020)

Esotracheal fistulas after esophageal atresia repair recur in 5 to 10 % of cases [1] [2] and lead to recurrent pneumonia or mediastinitis. Several surgical techniques are effective in closing an esotracheal fistula by thoracotomy or cervicotomy [3], but endoscopic success has never been published for this indication.
Periostin
Authors: Xiaowei Nie, Chenyou Shen, Jianxin Tan, Zhiyuan Wu, Wei Wang, Yuan Chen, Youai Dai, Xusheng Yang, Shugao Ye, Jingyu Chen, Jin-Song Bian
Journal: Circulation Research (2020)

POSTN (Periostin) is an ECM (extracellular matrix) protein involved in tissue remodeling in response to injury and a contributing factor in tumorigenesis, suggesting that POSTN plays a role in the pathogenesis of pulmonary hypertension (PH).We aimed to gain insight into the mechanistic contribution of POSTN in experimental mouse models of PH and correlate these findings with PH in humans.We used genetic epistasis approaches in human pulmonary artery endothelial cells (hPAECs), human pulmonary artery smooth muscle cells, and experimental mouse models of PH (Sugen 5416/hypoxia or chronic hypoxia) to discern the role of POSTN and its relationship to HIF (hypoxia-inducible factor)-1α signaling. We found that POSTN expression was correlated with the extent of PH in mouse models and in humans. Decreasing POSTN improved hemodynamic and cardiac responses in PH mice, blunted the release of growth factors and HIF-1α, and reversed the downregulated BMPR (bone morphogenetic protein receptor)-2 expression in hPAECs from patients with PH, whereas increasing POSTIN had the opposite effects and induced a hyperproliferative and promigratory phenotype in both hPAECs and human pulmonary artery smooth muscle cells. Overexpression of POSTN-induced activation of HIFs and increased the production of ET (endothelin)-1 and VEGF (vascular endothelial growth factor) in hPAECs. SiRNA-mediated knockdown of HIF-1α abolished the proangiogenic effect of POSTN. Blockade of TrkB (tyrosine kinase receptor B) attenuated the effect of POSTN on HIF-1α expression, while inhibition of HIF-1α reduced the expression of POSTN and TrkB. These results suggest that hPAECs produce POSTN via a HIF-1α-dependent mechanism.Our study reveals that POSTN expression is increased in human and animal models of PH and fosters PH development via a positive feedback loop between HIF-1α and POSTN during hypoxia. We propose that manipulating POSTIN expression may be an efficacious therapeutic target in the treatment of PH. Our results also suggest that POSTN may serve as a biomarker to estimate the severity of PH.
Limited role for bronchoalveolar lavage to exclude COVID-19 after negative upper respiratory tract swabs: a multicentre study
Authors: Pietro Geri, Francesco Salton, Lina Zuccatosta, Mario Tamburrini, Marco Biolo, Annalisa Busca, Mario Santagiuliana, Umberto Zuccon, Paola Confalonieri, Barbara Ruaro, Pierlanfranco D'Agaro, Stefano Gasparini, Marco Confalonieri
Journal: European Respiratory Journal (2020)

<b>Given the strong agreement between negative upper respiratory swabs and BAL, this study suggests that BAL has a limited role in the diagnosis of COVID-19 if thoracic imaging and upper respiratory swabs are concordantly negative</b>https://bit.ly/3gpBC75
Letter to the Editor: Clincal Implications and Thoughts on Heterogenous Treatment Strategies for Patients With Clinical Stage T1–3/N2 Lung Cancer
Authors: Donglai Chen, Chang Chen, Junmiao Wen, Yongbing Chen
Journal: Journal of the National Comprehensive Cancer Network (2020)

"Letter to the Editor: Clinical Implications and Thoughts on Heterogeneous Treatment Strategies for Patients With Clinical Stage T1–3/N2 Lung Cancer" published on Aug 2020 by National Comprehensive Cancer Network.
Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma
Authors: Jing Quan Lim, Dachuan Huang, Tiffany Tang, Daryl Tan, Yurike Laurensia, Rou-Jun Peng, Esther Kam Yin Wong, Daryl Ming Zhe Cheah, Burton Kuan Hui Chia, Jabed Iqbal, Nicholas Francis Grigoropoulos, Maarja-Liisa Nairismägi, Cedric Chuan Young Ng, Vikneswari Rajasegaran, Huangming Hong, Seok Jin Kim, Junhun Cho, Eric Tse, Benjamin Mow, Qi-Chun Cai, Li-Mei Poon, Qing-qing Cai, Jing Tan, Jason Yongsheng Chan, Johnathan Xiande Lim, Yeow Tee Goh, Colin Phipps, Olaf Rötzschke, Chee Leong Cheng, Jeslin Chian Hung Ha, Lay Poh Khoo, Yvonne Su Ming Loh, Rex Au-Yeung, Thomas Sau-Yan Chan, Yok-Lam Kwong, William Hwang, Won Seog Kim, Jin-Xin Bei, Tongyu Lin, Choon Kiat Ong, Soon Thye Lim
Journal: Leukemia (2020)
COVID-19—a very visible pandemic
Authors: Carina King, Lena Einhorn, Nele Brusselaers, Marcus Carlsson, Stefan Einhorn, Fredrik Elgh, Jonas Frisén, Åke Gustafsson, Stefan Hanson, Claudia Hanson, Thomas Hedner, Olle Isaksson, Anders Jansson, Åke Lundkvist, Jan Lötvall, Bo Lundback, Björn Olsen, Cecilia Söderberg-Nauclér, Anders Wahlin, Gunner Steineck, Anders Vahlne
Journal: The Lancet (2020)
Abstract 12754: Association of Aldh2 Gene Polymorphism With Cardiac Function Insufficiency After Myocardial Infarction in Chinese Han Population
Authors: Lijie Wang, Yu Haiyi, Wei Gao
Journal: Circulation (2019)

Introduction: A large number of people in East Asia carry single nucleotide mutations (SNPs) of aldehyde dehydrogenase 2 (Aldh2) gene that impair aldehyde dehydrogenase type 2. Aldh2 deficiency lea...
Hyaluronic Acid‐Based Bioink Composition Enabling 3D Bioprinting and Improving Quality of Deposited Cartilaginous Extracellular Matrix
Authors: Julia Hauptstein, Thomas Böck, Michael Bartolf‐Kopp, Leonard Forster, Philipp Stahlhut, Ali Nadernezhad, Gina Blahetek, Alma Zernecke‐Madsen, Rainer Detsch, Tomasz Jüngst, Jürgen Groll, Jörg Teßmar, Torsten Blunk
Journal: Advanced Healthcare Materials (2020)

In 3D bioprinting, bioinks with high concentrations of polymeric materials are frequently used to enable fabrication of 3D cell-hydrogel constructs with sufficient stability. However, this is often associated with restricted cell bioactivity and an inhomogeneous distribution of newly produced extracellular matrix (ECM). Therefore, this study investigates bioink compositions based on hyaluronic acid (HA), an attractive material for cartilage regeneration, which allow for reduction of polymer content. Thiolated HA and allyl-modified poly(glycidol) in varying concentrations are UV-crosslinked. To adapt bioinks to poly(ε-caprolactone) (PCL)-supported 3D bioprinting, the gels are further supplemented with 1 wt% unmodified high molecular weight HA (hmHA) and chondrogenic differentiation of incorporated human mesenchymal stromal cells is assessed. Strikingly, addition of hmHA to gels with a low polymer content (3 wt%) results in distinct increase of construct quality with a homogeneous ECM distribution throughout the constructs, independent of the printing process. Improved ECM distribution in those constructs is associated with increased construct stiffness after chondrogenic differentiation, as compared to higher concentrated constructs (10 wt%), which only show pericellular matrix deposition. The study contributes to effective bioink development, demonstrating dual function of a supplement enabling PCL-supported bioprinting and at the same time improving biological properties of the resulting constructs.