tbuckley/cabot-search huggingface dataset:
Amphiphilic Polyelectrolyte Graft Copolymers Enhance the Activity of Cyclic Dinucleotide STING Agonists
Authors: Dinh Chuong Nguyen, Daniel Shae, Hayden M. Pagendarm, Kyle W. Becker, Mohamed Wehbe, Kameron V. Kilchrist, Lucinda E. Pastora, Christian R. Palmer, Pedro Seber, Plamen P. Christov, Craig L. Duvall, John T. Wilson
Journal: Advanced Healthcare Materials (2020)

Cyclic dinucleotide (CDN) agonists of stimulator of interferon genes (STING) hold great therapeutic potential, but their activity is hindered by poor drug-like properties that restrict cytosolic bioavailability. Here, this challenge is addressed through the synthesis and evaluation of a novel series of PEGMA-co-DEAEMA-co-BMA copolymers with pH-responsive, membrane-destabilizing activity to enhance intracellular delivery of the CDN, cGAMP. Copolymers are synthesized with PEGMA of two different molecular weights (300 and 950 Da) and over a range of PEG mass fraction and polymer molecular weight, and relationships between copolymer structure, self-assembly, endosomal escape, and cGAMP activity are elucidated. A subset of polymers that self-assembled into 50-800 nm nanoparticles is identified, which can be loaded with cGAMP via a simple mixing strategy, resulting in significantly enhanced immunostimulatory activity. Increased cGAMP activity is found to be highly correlated with the capacity of carriers to enhance intracellular CDN uptake and to promote endosomal destabilization, findings that establish efficient cytosolic delivery as a criterion for CDN carriers. Additionally, it is demonstrated that a lead CDN carrier formulation can enhance STING activation in vivo in a model of intratumoral immunotherapy. Collectively, these investigations demonstrate the utility of PEGMA-co-DEAEMA-co-BMA copolymers as carriers for CDNs and potentially other cytosolically-acting drug cargo.
Flexible Adipose‐Vascular Tissue Assembly Using Combinational 3D Printing for Volume‐Stable Soft Tissue Reconstruction
Authors: Won‐Woo Cho, Byoung Soo Kim, Minjun Ahn, Yeon Hee Ryu, Dong‐Heon Ha, Jeong Sik Kong, Jong‐Won Rhie, Dong‐Woo Cho
Journal: Advanced Healthcare Materials (2020)

Abstract A new concept, assembling cell‐laden tissue modules, is for the first time proposed for soft tissue engineering. Adipose‐vascular tissue modules composed of a synthetic polymer‐based substructure and customized bioinks using planar 3D cell printing are engineered. Such tissue modules are systematically assembled into a synthetic polymer‐based module holder fabricated with rotational 3D printing, resulting in the development of a flexible and volumetric tissue assembly. Whereas most of the previous studies about the construction of adipose tissue are limited to hypoxia, poor vascularization, rapid resorption, and mismatch in mechanical properties, it is aimed to realize the construction of nonhypoxic, flexible, and volume‐stable tissue assembly in this study. The significance of engineered tissue assembly is proven through various in vitro and in vivo evaluations. In particular, stable volume and remarkable neovascularization/adipogenesis are observed in the implanted assembly over four weeks. Interestingly, the size of newly formed lipid droplets and the remodeled morphology in the assembly are comparable to those in native adipose tissue. As far as it is known, this work is a first report suggesting a cell printing‐based tissue assembly for functional reconstruction of soft tissue.
17129 Comparative analysis of clinical benefits provided by two facial daily care regimens with the antioxidants ascorbyl glucoside and tocopheryl glucoside for 8 weeks in Brazilian women
Authors: Ana Coutinho, Victor Georgescu, Christine Coutanceau, Daniel Redoules, Fabio Sanchez, Fernanda Chaves Beltrão
Journal: Journal of the American Academy of Dermatology (2020)
Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer
Authors: Anant Ramaswamy, Vikas Ostwal, Atul Sharma, Prabhat Bhargava, Sujay Srinivas, Mahesh Goel, Shraddha Patkar, Sarika Mandavkar, Poonam Jadhav, Manali Parulekar, Amitkumar Choudhari, Sudeep Gupta
Journal: JAMA Oncology (2020)

<h3>Importance</h3> There is therapeutic uncertainty regarding use of combination or single-agent chemotherapy in the treatment of patients with gallbladder cancer who experience disease progression after first-line chemotherapy. <h3>Objective</h3> To compare the efficacy of capecitabine plus irinotecan (CAPIRI) vs irinotecan (IRI) alone in patients with advanced gallbladder cancer (GBC) who have disease progression after gemcitabine-based first-line treatment. <h3>Design, Setting, and Participants</h3> The GB-SELECT trial was a multicenter, open-label, phase 2, randomized clinical trial of CAPIRI vs IRI alone for treatment of gallbladder cancer in patients who had disease progression after prior gemcitabine-based chemotherapy.The study was carried out in 2 tertiary care institutions in India. Patients aged between 18 and 70 years with histopathologic diagnosis of adenocarcinoma gallbladder, advanced or metastatic disease, previous treatment with gemcitabine-based chemotherapy, adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between August 2018 and January 2020. The data were analyzed for this report with cutoff on May 19, 2020. <h3>Interventions</h3> Patients were randomized 1:1 to receive capecitabine, 1700 mg/m<sup>2</sup>per day, on days 1 to 14 plus intravenous irinotecan, 200 mg/m<sup>2</sup>, on day 1 or intravenous irinotecan, 240 mg/m<sup>2</sup>, on day 1, in 21-day cycles until disease progression or unacceptable toxic effects. <h3>Main Outcomes and Measures</h3> The primary end point was overall survival (OS) at 6 months. The secondary end points were progression-free survival and quality of life. <h3>Results</h3> A total of 98 patients were randomized, 49 in each arm, with median (range) age of 51 (29-70) years, with 60 (61%) being women. In the CAPIRI vs IRI arms, the number of deaths at 6 months, 6-month OS, and median OS were 35, 34, 38.4% (95% CI, 24.2%-52.6%) and 5.16 (95% CI, 4.26-6.06) months vs 34, 29, 54.2% (95% CI, 39.4%-69.0%) and 6.28 (95% CI, 4.25-8.30) months, respectively, with a hazard ratio of 1.02 (95% CI, 0.64-1.49,<i>P</i> = .93). There were no chemotherapy-related deaths but more patients required dose modification in CAPIRI compared with the IRI arm (13 [27%] vs 4 [9%], respectively,<i>P</i> = .03). <h3>Conclusions and Relevance</h3> There was no significant difference in OS between treatment with capecitabine plus irinotecan or irinotecan alone among previously treated patients with gallbladder cancer. Single-agent irinotecan should be the preferred treatment option for such patients. <h3>Trial Registration</h3> CTRI/2017/10/010112
388P Biosimilar TAB008 compared with bevacizumab in advanced non-squamous, non-small cell, EGFR wildtype lung cancer patients
Authors: Z. Zhou, S. Lu, S. Qin, J. Chen, K. Gu, P. Sun, Y. Pan, G. Yu, K. Ma, J. Shi, Y. Sun, L. Yang, P. Chen, A. Liu, J. He, X. Li, L. Wang
Journal: Annals of Oncology (2020)
Glutamine-Directed Migration of Cancer-Activated Fibroblasts Facilitates Epithelial Tumor Invasion
Authors: Aida Mestre-Farrera, Marina Bruch-Oms, Raúl Peña, José Rodríguez-Morató, Lorena Alba-Castellón, Laura Comerma, Miguel Quintela-Fandino, Mireia Duñach, Josep Baulida, Óscar J. Pozo, Antonio García de Herreros
Journal: Cancer Research (2020)

Abstract Tumors are complex tissues composed of transformed epithelial cells as well as cancer-activated fibroblasts (CAF) that facilitate epithelial tumor cell invasion. We show here that CAFs and other mesenchymal cells rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to inhibition of glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low glutamine conditions. CAFs also invaded a Matrigel matrix following a glutamine concentration gradient and enhanced the invasion of tumor cells when both cells were cocultured. Accordingly, glutamine directed invasion of xenografted tumors in immunocompromised mice. Stimulation of glutamine-driven epithelial tumor invasion by fibroblasts required previous CAF activation, which involved the TGFβ/Snail1 signaling axis. CAFs moving toward Gln presented a polarized Akt2 distribution that was modulated by the Gln-dependent activity of TRAF6 and p62 in the migrating front, and depletion of these proteins prevented Akt2 polarization and Gln-driven CAF invasion. Our results demonstrate that glutamine deprivation promotes CAF migration and invasion, which in turn facilitates the movement of tumor epithelial cells toward nutrient-rich territories. These results provide a novel molecular mechanism for how metabolic stress enhances invasion and metastasis. Significance: Cancer-associated fibroblasts migrate and invade toward free glutamine and facilitate invasion of tumor epithelial cells, accounting for their movement away from the hostile conditions of the tumor towards nutrient-rich adjacent tissues.
Abstract PO-19: Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis
Authors: Chun Gong, Joanna A. Krupka, Jane Gao, Nicholas F. Grigoropoulos, Francesco Cucco, Sharon Barrans, De Los Mozos Igor, Zhou Peixun, Forde Sorca, Matthews Jamie, Burke Amos, Sze Siu Kwan, Beer Philip, Burton Cathy, Campbell Peter, Rand Vikki, Turner Suzanne, Ule Jernej, Roman Eve, Tooze Reuben, Oellerich Thomas, Du Ming, Samarajiwa Shamith, Daniel J. Hodson
Journal: Blood Cancer Discovery (2020)

Abstract DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also commonly found in MYC-translocated diffuse large B-cell lymphoma. We reveal functional cooperation between mutant DDX3X and MYC in ex vivo cultured human germinal center B cells. By integrating results of iCLIP, ribosome profiling, and proteomics, we show WT DDX3X promotes the translation of mRNAs encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations act to buffer the effect of abrupt MYC expression and moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells subsequently restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y-chromosome homologue that is normally expressed exclusively in testis. These findings show how sequential dysregulation of DDX3X and DDX3Y acts to titrate global protein synthesis to suit the stage-specific needs of developing lymphoma cells and identify DDX3Y as an attractive, male-specific therapeutic target absent from normal human B cells but required for the survival of male lymphomas. Citation Format: Chun Gong, Joanna A. Krupka, Jane Gao, Nicholas F. Grigoropoulos, Francesco Cucco, Sharon Barrans, De Los Mozos Igor, Zhou Peixun, Forde Sorca, Matthews Jamie, Burke Amos, Sze Siu Kwan, Beer Philip, Burton Cathy, Campbell Peter, Rand Vikki, Turner Suzanne, Ule Jernej, Roman Eve, Tooze Reuben, Oellerich Thomas, Du Ming, Samarajiwa Shamith, Daniel J. Hodson. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-19.
17888 The influence of p16 immunohistochemistry on diagnosis and management recommendation of melanocytic neoplasms by dermatopathologists: A single-institution prospective study
Authors: Jessica Terrell, Iryna Rybak, Yue Lyu, Thomas Konia, Maxwell Fung, Lihong Qi, Maija Kiuru
Journal: Journal of the American Academy of Dermatology (2020)
13813 Development and validation of a multigene signature for identification of cutaneous squamous cell carcinoma patients at high risk for regional or distant metastases
Authors: Ashley Wysong, Kyle R. Covington, Sarah J. Kurley, Clare Johnson, Robert W. Cook, Jason G. Newman, Chrysalyne D. Schmults, Sarah T. Arron
Journal: Journal of the American Academy of Dermatology (2020)
Adaptive T-cell immunity controls senescence-prone MyD88- or CARD11-mutant B-cell lymphomas
Authors: Maurice Reimann, Jens Schrezenmeier, Paulina Richter-Pechanska, Anna Dolnik, Timon Pablo Hick, Kolja Schleich, Xiurong Cai, Dorothy N. Y. Fan, Philipp Lohneis, Sven Maßwig, Sophy Denker, Antonia Busse, Gero Knittel, Ruth Flümann, Dorothee Childs, Liam Childs, Ana-Maria Gätjens-Sanchez, Lars Bullinger, Andreas Rosenwald, Hans Christian Reinhardt, Clemens A. Schmitt
Journal: Blood (2020)
Initiatives to Reduce Maternal Mortality and Severe Maternal Morbidity in the United States
Authors: Roy Ahn, Grace P. Gonzalez, Britta Anderson, Catherine J. Vladutiu, Erin R. Fowler, Leticia Manning
Journal: Annals of Internal Medicine (2020)

Maternal mortality and severe maternal morbidity are critical health issues in the United States, with unacceptably high rates and racial, ethnic, and geographic disparities. Various factors contribute to these adverse maternal health outcomes, ranging from patient-level to health system-level factors. Furthermore, a majority of pregnancy-related deaths are preventable. This review briefly describes the epidemiology of maternal mortality and severe maternal morbidity in the United States and discusses selected initiatives to reduce maternal mortality and severe maternal morbidity in the areas of data and surveillance; clinical workforce training and patient education; telehealth; comprehensive models and strategies; and clinical guidelines, protocols, and bundles. Related Health Resources and Services Administration initiatives are also described.
Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors
Authors: Andrew Dunbar, Kelly L. Bolton, Sean M. Devlin, Francisco Sanchez-Vega, Jianjiong Gao, Jodi V. Mones, Jonathan Wills, Daniel Kelly, Mirko Farina, Keith B. Cordner, Young Park, Sirish Kishore, Krishna Juluru, Neil M. Iyengar, Ross L. Levine, Ahmet Zehir, Wungki Park, Alok A. Khorana, Gerald A. Soff, Simon Mantha
Journal: Blood (2020)
Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial
Authors: Bardia Nourbakhsh, Nisha Revirajan, Bridget Morris, Christian Cordano, Jennifer Creasman, Michael Manguinao, Kristen Krysko, Alice Rutatangwa, Caroline Auvray, Salman Aljarallah, Chengshi Jin, Ellen Mowry, Charles McCulloch, Emmanuelle Waubant
Journal: The Lancet Neurology (2020)
Gastrointestinal Stromal Tumor Incidentally Detected on 18F-Fluciclovine PET/CT
Authors: Kesav Raghavan, Robert R. Flavell, Antonio C. Westphalen, Spencer C. Behr
Journal: Clinical Nuclear Medicine (2020)

We present a case of metastatic gastrointestinal stromal tumor incidentally detected on 18F-fluciclovine PET/CT. A 68-year-old man with history of intermediate-risk prostate cancer (Gleason score 4 + 3 = 7; pT2cN0M0) previously treated with retropubic radical prostatectomy, adjuvant whole pelvis radiation, and androgen deprivation therapy (leuprolide) presented with slowly rising serum prostate-specific antigen over 3 years, concerning for recurrent prostate cancer. To identify potential sites of recurrent disease, an 18F-fluciclovine PET/CT was obtained. Multiple tracer-avid mesenteric masses and enlarged lymph nodes were found throughout the abdomen and pelvis, later biopsy-proven to reflect metastatic gastrointestinal stromal tumor.
Prognosis in Hypertrophic Cardiomyopathy With Contrast-Enhanced Cardiac Magnetic Resonance: The Future Looks Bright⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Michael Salerno, Christopher M. Kramer
Journal: Journal of the American College of Cardiology (2010)
1O KEYNOTE-522 Asian subgroup: Phase III study of neoadjuvant pembrolizumab (pembro) vs placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo for early triple-negative breast cancer (TNBC)
Authors: R. Dent, J. Cortes, L. Pusztai, H.L. McArthur, S. Kuemmel, J. Bergh, C. Denkert, Y.H. Park, R. Hui, N. Harbeck, M. Takahashi, T. Foukakis, P.A. Fasching, F. Cardoso, L. Jia, E. Jensen, V. Karantza, G. Aktan, J. O'Shaughnessy, P. Schmid
Journal: Annals of Oncology (2020)
Myocardial remodelling after withdrawing therapy for heart failure in patients with recovered dilated cardiomyopathy: insights from <scp>TRED‐HF</scp>
Authors: Brian P. Halliday, Ruth Owen, John Gregson, Vassilios S. Vassiliou, Xiuyu Chen, Ricardo Wage, Amrit S. Lota, Zohya Khalique, Upasana Tayal, Daniel J. Hammersley, Richard E. Jones, A. John Baksi, Martin R. Cowie, John G.F. Cleland, Dudley J. Pennell, Sanjay K. Prasad
Journal: European Journal of Heart Failure (2020)

Aims To characterize adverse ventricular remodelling after withdrawing therapy in recovered dilated cardiomyopathy (DCM). Methods and results TRED‐HF was a randomized controlled trial with a follow‐on single‐arm cross‐over phase that examined the safety and feasibility of therapy withdrawal in patients with recovered DCM over 6 months. The primary endpoint was relapse of heart failure defined by (i) a reduction in left ventricular (LV) ejection fraction &gt;10% and to &lt;50%, (ii) &gt;10% increase in LV end‐diastolic volume and to above the normal range, (iii) a twofold rise in N‐terminal pro‐B‐type natriuretic peptide and to &gt;400 ng/L, or (iv) evidence of heart failure. LV mass, LV and right ventricular (RV) global longitudinal strain (GLS) and extracellular volume were measured using cardiovascular magnetic resonance at baseline and follow‐up (6 months or relapse) for 48 patients. LV cell and extracellular matrix masses were derived. The effect of withdrawing therapy, stratified by relapse and genotype, was investigated in the randomized and follow‐on phases. In the randomized comparison, withdrawing therapy led to an increase in mean LV mass [5.4 g/m 2 ; 95% confidence interval (CI) 1.3–9.5] and cell mass (4.2 g/m 2 ; 95% CI 0.5–8.0) and a reduction in LV (3.5; 95% CI 1.6–5.5) and RV (2.4; 95% CI 0.1–4.7) GLS . In a non‐randomized comparison of all patients ( n = 47) who had therapy withdrawn in either phase , there was an increase in LV mass (6.2 g/m 2 ; 95% CI 3.6–8.9; P = 0.0001), cell mass (4.0 g/m 2 ; 95% CI 1.8–6.2; P = 0.0007) and matrix mass (1.7 g/m 2 ; 95% CI 0.7–2.6; P = 0.001) and a reduction in LV GLS (2.7; 95% CI 1.5–4.0; P = 0.0001). Amongst those who had therapy withdrawn and did not relapse , similar changes were observed ( n = 28; LV mass: 5.1 g/m 2 , 95% CI 1.5–8.8, P = 0.007; cell mass: 3.7 g/m 2 , 95% CI 0.3–7.0, P = 0.03; matrix mass: 1.7 g/m 2 , 95% CI 0.4–3.0, P = 0.02; LV GLS: 1.7, 95% CI 0.1–3.2, P = 0.04). Patients with TTN variants ( n = 10) who had therapy withdrawn had a greater increase in LV matrix mass (mean effect of TTN : 2.6 g/m 2 ; 95% CI 0.4–4.8; P = 0.02). Conclusion In TRED‐HF, withdrawing therapy caused rapid remodelling, with early tissue and functional changes, even amongst patients who did not relapse.
Timing of Prenatal Care Initiation in the Health Resources and Services Administration Health Center Program in 2017
Authors: Carolyn Robbins, Samantha Martocci
Journal: Annals of Internal Medicine (2020)

Early prenatal care is vital for improving maternal health outcomes and health behaviors, but medically vulnerable and underserved populations are less likely to begin prenatal care in the first trimester. In 2017, the Health Center Program provided safety-net care to more than 27 million persons, including 573 026 prenatal patients, at approximately 12 000 sites across the United States and U.S. jurisdictions. As part of a mandatory reporting requirement, health centers tracked whether patients initiated prenatal care in their first trimester of pregnancy. To identify health center characteristics associated with the initiation of prenatal care in the first trimester, as well as actionable steps policymakers, providers, and health centers can take to promote early initiation of prenatal care. Secondary analysis of cross-sectional data from the 2017 Uniform Data System. The United States and 8 U.S. jurisdictions. Health center grantees with prenatal patients (n = 1281). Multinomial logistic regression (adjusted for state or jurisdiction clustering) was used to identify health center characteristics associated with achievement of the Healthy People 2020 baseline (77.1%) and target (84.8%) for women receiving prenatal care in the first trimester (Maternal, Infant, and Child Health Objective 10.1). Overall, 57.4% of health centers met the Healthy People 2020 baseline (mean, 78%; median, 81%), and 37.9% met the Healthy People 2020 target. Several characteristics were positively associated with meeting the baseline (larger proportion of prenatal patients aged 20 to 24 years) and target (more total patients, prenatal care by referral only, a larger proportion of prenatal patients aged 25 to 44 or ≥45 years, and a larger proportion of White or privately insured patients). Other characteristics were negatively associated with the baseline (location outside New England, location in a rural area, and a large proportion of prenatal patients aged <15 years) and target (more prenatal patients, location outside New England, provision of prenatal care to women living with HIV, and more uninsured patients or patients eligible for both Medicare and Medicaid). The data set is at the health center grantee level and does not contain information on timing or quality of follow-up prenatal care. Most health centers met the Healthy People 2020 baseline, but opportunities for improvement remain and the Healthy People 2020 target is still a challenge for many health centers. Policymakers, providers, and health centers can learn from high-achieving centers to promote early initiation of prenatal care among medically vulnerable and underserved populations. Health Resources and Services Administration.