tbuckley/cabot-search huggingface dataset:
Effective control of tumor growth through spatial and temporal control of theranostic sodium iodide symporter (<i>NIS</i>) gene expression using a heat-inducible gene promoter in engineered mesenchymal stem cells
Authors: Mariella Tutter, Christina Schug, Kathrin A. Schmohl, Sarah Urnauer, Nathalie Schwenk, Matteo Petrini, Wouter J. M. Lokerse, Christian Zach, Sibylle Ziegler, Peter Bartenstein, Wolfgang A. Weber, Ernst Wagner, Lars H. Lindner, Peter J. Nelson, Christine Spitzweg
Journal: Theranostics (2020)

Purpose: The tumor homing characteristics of mesenchymal stem cells (MSCs) make them attractive vehicles for the tumor-specific delivery of therapeutic agents, such as the sodium iodide symporter (NIS). NIS is a theranostic protein that allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression by radioiodine imaging as well as the therapeutic application of 131I. To gain local and temporal control of transgene expression, and thereby improve tumor selectivity, we engineered MSCs to express the NIS gene under control of a heat-inducible HSP70B promoter (HSP70B-NIS-MSCs). Experimental Design: NIS induction in heat-treated HSP70B-NIS-MSCs was verified by 125I uptake assay, RT-PCR, Western blot and immunofluorescence staining. HSP70B-NIS-MSCs were then injected i.v. into mice carrying subcutaneous hepatocellular carcinoma HuH7 xenografts, and hyperthermia (1 h at 41°C) was locally applied to the tumor. 0 - 72 h later radioiodine uptake was assessed by 123I-scintigraphy. The most effective uptake regime was then selected for 131I therapy. Results: The HSP70B promoter showed low basal activity in vitro and was significantly induced in response to heat. In vivo, the highest tumoral iodine accumulation was seen 12 h after application of hyperthermia. HSP70B-NIS-MSC-mediated 131I therapy combined with hyperthermia resulted in a significantly reduced tumor growth with prolonged survival as compared to control groups. Conclusions: The heat-inducible HSP70B promoter allows hyperthermia-induced spatial and temporal control of MSC-mediated theranostic NIS gene radiotherapy with efficient tumor-selective and temperature-dependent accumulation of radioiodine in heat-treated tumors.
Long‐term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE‐1)*
Authors: K. Papp, A. Menter, C. Leonardi, J. Soung, S. Weiss, R. Pillai, A. Jacobson
Journal: British Journal of Dermatology (2020)

Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks.To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment.At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re-treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events.Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed.These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.
COVID-19: community CPAP and NIV should be stopped unless medically necessary to support life
Authors: Joseph Barker, Oluwatobiloba Oyefeso, David Koeckerling, Nadeesha Lakmal Mudalige, Daniel Pan
Journal: Thorax (2020)

Dear Editor,

Data from the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) outbreak suggest high viral load at the time of transmission is associated with worse clinical outcomes.1 Non-invasive ventilation (NIV), including CPAP, is currently listed by the WHO as a high-risk aerosol-generating procedure putting healthcare workers at risk and necessitates the use of personal protective equipment.2 3

The current UK guidance does not account for high-dose viral transmission risk to family and carers in patients using community NIV and CPAP for treatment …
Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1
Authors: Jamie O. Brett, Marina Arjona, Mika Ikeda, Marco Quarta, Antoine de Morrée, Ingrid M. Egner, Luiz A. Perandini, Heather D. Ishak, Armon Goshayeshi, Daniel I. Benjamin, Pieter Both, Cristina Rodríguez-Mateo, Michael J. Betley, Tony Wyss-Coray, Thomas A. Rando
Journal: Nature Metabolism (2020)
Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial
Authors: Junjie Li, Keda Yu, Da Pang, Changqin Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Peifen Fu, Yuan Sheng, Guojun Zhang, Yali Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Xiang Qu, Jinhai Tang, Ouchen Wang, Zhimin Fan, Guoqin Jiang, Jin Zhang, Jiandong Wang, Hongwei Zhang, Shui Wang, Jianguo Zhang, Feng Jin, Nanyan Rao, Binlin Ma, Pingqing He, Binghe Xu, Zhigang Zhuang, Jianfeng Wang, Qiang Sun, Xiaofeng Guo, Miao Mo, Zhimin Shao
Journal: Journal of Clinical Oncology (2020)

Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated.This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS).Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms.Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.
Transvalvular Flow Rate Determines Prognostic Value of Aortic Valve Area in Aortic Stenosis
Authors: Mayooran Namasivayam, Wei He, Timothy W. Churchill, Romain Capoulade, Shiying Liu, Hang Lee, Jacqueline S. Danik, Michael H. Picard, Philippe Pibarot, Robert A. Levine, Judy Hung
Journal: Journal of the American College of Cardiology (2020)
Metastatic extent predicts survival as patients with metastatic castration-resistant prostate cancer are treated with <sup>177</sup>Lu-PSMA radioligand therapy
Authors: Finn Edler von Eyben, Harshad R. Kulkarni, Richard P. Baum
Journal: Theranostics (2020)

PSMA based radioligand is a new investigational drug for treatment of metastatic multidrug-resistant and castration-resistant prostate cancer.Prognostic factors point to above and below average overall survival (OS) after the treatment.Kessel et al. [Theranostics 2019;9:4841-8] reported for the first time that two sites of visceral metastases, lungs and liver, differed in impact on OS after treatment with 177 Lu PSMA 617.Treatment with established drugs showed the same trend.The difference in OS between the sites is independent of the type of treatment and can reflect changes in tumor biology during the progression of metastatic prostate cancer.
Gender and occupational allergy: Report from the task force of the EAACI Environmental and Occupational Allergy Interest Group
Authors: Gianna Moscato, Christian Apfelbacher, Knut Brockow, Chiara Eberle, Jon Genuneit, Charlotte G. Mortz, Cristina Quecchia, Santiago Quirce, Andrea Siracusa, Susan Mary Tarlo, Vera van Kampen, Jolanta Walusiak‐Skorupa, Monika Raulf
Journal: Allergy (2020)

Abstract Women's work has traditionally been considered less hazardous to health in comparison with men's work. The increased women's participation in the workforce has led to an increased attention to women's working conditions. Women and men are unequally represented in individual professions or sectors (horizontal segregation), with women also under‐represented in leadership positions (vertical segregation). The selection of specific occupations can result in differences between types and levels of occupational exposures among women and men and can affect prevalence of occupational allergy. Gender distribution of work‐related asthma appears to vary across countries without clear global difference. Occupational rhinitis tends to be higher in women, although is not clear if this is related to a sex/gender effect or to differences in work exposure. Women are more likely to have occupational contact dermatitis, mainly due to wet work. No clear effects of gender on rates of hypersensitivity pneumonitis have been shown. Besides variation in exposures, physical and physiological characteristics, different behaviours and health consciousness have an impact on the occupational health hazards of women and men. Occupational allergy health promotion strategies need to consider approaches for women and men adjusted by gender, and legislative actions similarly could be implemented in a more gender‐sensitive way .
A homozygous deletion in the SLC19A1 gene as a cause of folate-dependent recurrent megaloblastic anemia
Authors: Michael Svaton, Karolina Skvarova Kramarzova, Veronika Kanderova, Andrea Mancikova, Petr Smisek, Pavel Jesina, Jakub Krijt, Blanka Stiburkova, Robert Dobrovolny, Jitka Sokolova, Violeta Bakardjieva-Mihaylova, Elena Vodickova, Marketa Rackova, Jan Stuchly, Tomas Kalina, Jan Stary, Jan Trka, Eva Fronkova, Viktor Kozich
Journal: Blood (2020)
Genome sequence of Gossypium herbaceum and genome updates of Gossypium arboreum and Gossypium hirsutum provide insights into cotton A-genome evolution
Authors: Gai Huang, Zhiguo Wu, Richard G. Percy, Mingzhou Bai, Yang Li, James E. Frelichowski, Jiang Hu, Kun Wang, John Z. Yu, Yuxian Zhu
Journal: Nature Genetics (2020)

Abstract Upon assembling the first Gossypium herbaceum (A 1 ) genome and substantially improving the existing Gossypium arboreum (A 2 ) and Gossypium hirsutum ((AD) 1 ) genomes, we showed that all existing A-genomes may have originated from a common ancestor, referred to here as A 0 , which was more phylogenetically related to A 1 than A 2 . Further, allotetraploid formation was shown to have preceded the speciation of A 1 and A 2 . Both A-genomes evolved independently, with no ancestor–progeny relationship. Gaussian probability density function analysis indicates that several long-terminal-repeat bursts that occurred from 5.7 million years ago to less than 0.61 million years ago contributed compellingly to A-genome size expansion, speciation and evolution. Abundant species-specific structural variations in genic regions changed the expression of many important genes, which may have led to fiber cell improvement in (AD) 1 . Our findings resolve existing controversial concepts surrounding A-genome origins and provide valuable genomic resources for cotton genetic improvement.
Coronavirus Disease 2019 (COVID-19) and Mental Health for Children and Adolescents
Authors: Ezra Golberstein, Hefei Wen, Benjamin F. Miller
Journal: JAMA Pediatrics (2020)

Coronavirus Disease 2019 (COVID-19) and Mental Health for Children and AdolescentsStates and localities are taking unprecedented steps to respond to the public health threat posed by the coronavirus disease 2019 (COVID-19) pandemic.Among the measures intended to promote social distancing, many schools have been closed and classes shifted to homebased distance-learning models.The first school closures began in mid-March 2020 and some states have already closed schools for the rest of the academic year.Nearly all of the 55 million students in kindergarten through 12th grade in the US are affected by these closures.School closures substantially disrupt the lives of students and their families and may have consequences for child health.As such, we must consider the potential associations school closures have with children's well-being and what can be done to mitigate them.Children and adolescents are generally healthy and do not require much health care outside of regular checkups and immunizations.However, mental health care is very important for children and adolescents.Most mental health disorders begin in childhood, making it essential that mental health needs are identified early and treated during this sensitive time in child development. 1f untreated, mental health problems can lead to many negative health and social outcomes.The COVID-19 pandemic may worsen existing mental health problems and lead to more cases among children and adolescents because of the unique combination of the public health crisis, social isolation, and economic recession.Economic downturns are associated with increased mental health problems for youth that may be affected by the ways that economic downturns affect adult unemployment, adult mental health, and child maltreatment. 2ducators, administrators, and policy makers must minimize the disruptions that school closures will have on academic development.Schools offer many other critical services to students outside of education.For example, schools are a major source of nutrition for many students, and ensuring food security has been a common component of school closure plans.However, other services are equally essential to children's health and must be addressed.One potentially overlooked role played by schools is the delivery of health care, and especially of mental health services.Schools have long served as a de facto mental health system for many children and adolescents. 3Data from the nationally representative National Survey of Drug Use and Health (NSDUH) include information on mental health services for children age 12 to 17 years and illustrate the implications of school closures on access to mental health services.An analysis of the 2014 NSDUH by found that 13.2% of adolescents received some sort of mental health ser-
Hematopoiesis and Cardiovascular Disease
Authors: Wolfram C. Poller, Matthias Nahrendorf, Filip K. Swirski
Journal: Circulation Research (2020)

A central feature of atherosclerosis, the most prevalent chronic vascular disease and root cause of myocardial infarction and stroke, is leukocyte accumulation in the arterial wall. These crucial immune cells are produced in specialized niches in the bone marrow, where a complex cell network orchestrates their production and release. A growing body of clinical studies has documented a correlation between leukocyte numbers and cardiovascular disease risk. Understanding how leukocytes are produced and how they contribute to atherosclerosis and its complications is, therefore, critical to understanding and treating the disease. In this review, we focus on the key cells and products that regulate hematopoiesis under homeostatic conditions, during atherosclerosis and after myocardial infarction.
Coronaviruses hijack the complement system
Authors: C. Matthias Wilk
Journal: Nature reviews. Immunology (2020)

Hydroxychloroquine: small effects in mild diseaseThis preprint reports a double-blind, randomized clinical trial of 62 patients to assess the efficacy of hydroxychloroquine (HCQ) in mild COVID-19.Patients in the treatment arm received 400 mg HCQ per day for 5 days.Fever and cough resolved on average 1 day earlier with HCQ, although the distribution of symptomatic patients at day 0 was not even between groups.No patients receiving HCQ progressed to severe disease, whereas 4 of 31 patients in the control arm progressed.Few clinical data and no viral load measurements were reported, limiting the conclusions that can be drawn from this trial.This study suggests relative efficacy for patients with mild disease and warrants larger clinical trials, but the effects of HCQ on patients with more severe COVID-19 remain unknown.
Patient-Reported Fatigue Scores in Cancer Patients with Chemotherapy-Induced Anemia Treated with Erythropoietic-Stimulating Agents (ESAs).
Authors: Tanya Burton, David Hoaglin, Kay Larholt, Elizabeth Apgar, Chris Pashos, Brahim Bookhart, Mitra Corral, Catherine Tak Piech, R. scott McKenzie
Journal: Blood (2008)
Oral minoxidil improves background hair thickness in lichen planopilaris
Authors: Sergio Vañó-Galván, Lara Trindade de Carvalho, David Saceda-Corralo, Rita Rodrigues-Barata, Karolina L. Kerkemeyer, Rodney D. Sinclair, Ángela Hermosa-Gelbard, Óscar M. Moreno-Arrones, Juan Jimenez-Cauhe, Bevin Bhoyrul
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 14884: Obesity is a Major Driver of Obstruction and Heart Failure in Hypertrophic Cardiomyopathy: Results From the International Share Registry
Authors: Carlo Fumagalli, Niccolò Maurizi, Justin Vincent-Tompkins, Carolyn Y Ho, Sharlene M Day, Euan Ashley, Michelle Michels, Steven D Colan, Daniel Jacoby, Iacopo Olivotto
Journal: Circulation (2018)

Introduction: Obesity is a predictor of left ventricular mass and disease progression in hypertrophic cardiomyopathy (HCM). However, the extent to which body mass index (BMI) influences clinical pr...
Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103<sup>+</sup>conventional dendritic cells
Authors: Yifan Zhou, Natalie Slone, Taylor T Chrisikos, Oleksandr Kyrysyuk, Rachel L Babcock, Yusra B Medik, Haiyan S Li, Eugenie S Kleinerman, Stephanie S Watowich
Journal: Journal for ImmunoTherapy of Cancer (2020)

Type 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+ cDC1s in mice, CD141+ cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied.We generated murine CD103+ cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+ cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+ cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+ cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+ cDC1s.In vitro-generated CD103+ cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, and demonstrated antigen cross-presentation activity on stimulation with the toll-like receptor 3 agonist polyinosinic:polycytidylic acid (poly I:C). In vitro-generated CD103+ cDC1s also migrated to TdLNs following poly I:C treatment and intratumoral delivery. Vaccination with poly I:C-activated and tumor antigen-loaded CD103+ cDC1s enhanced tumor infiltration of tumor antigen-specific and interferon-γ+ CD8+ T cells, and suppressed melanoma and osteosarcoma growth. CD103+ cDC1s showed superior antitumor efficacy compared with MoDC vaccination, and led to complete regression of 100% of osteosarcoma tumors in combination with CTLA-4 antibody-mediated checkpoint blockade. In vitro-generated CD103+ cDC1s effectively protected mice from pulmonary melanoma and osteosarcoma metastases.Our data indicate an in vitro-generated CD103+ cDC1 vaccine elicits systemic and long-lasting tumor-specific T cell-mediated cytotoxicity, which restrains primary and metastatic tumor growth. The CD103+ cDC1 vaccine was superior to MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade.
Quantifying the prevalence and adaptiveness of behavioral rationalizations
Authors: Warren Tierney, Eric Luis Uhlmann
Journal: Behavioral and Brain Sciences (2020)

Abstract Critical aspects of the “rationality of rationalizations” thesis are open empirical questions. These include the frequency with which past behavior determines attitudes (as opposed to attitudes causing future behaviors), the extent to which post hoc justifications take on a life of their own and shape future actions, and whether rationalizers experience benefits in well-being, social influence, performance, or other desirable outcomes.
Comparison of outcomes after differentiated thyroid cancer surgery performed with and without energy devices: A population-based cohort study using a nationwide database in Japan
Authors: Takaaki Konishi, Michimasa Fujiogi, Takayoshi Niwa, Kojiro Morita, Hiroki Matsui, Kiyohide Fushimi, Masahiko Tanabe, Yasuyuki Seto, Hideo Yasunaga
Journal: International Journal of Surgery (2020)
A Phase I, Open Label, Multicenter Trial of Oral Azacitidine (CC-486) Plus R-CHOP in Patients with High-Risk, Previously Untreated Diffuse Large B-Cell Lymphoma, Grade 3B Follicular Lymphoma, or Transformed Lymphoma
Authors: Peter Martin, Nancy L. Bartlett, Ildefonso Ismael Rodriguez Rivera, Maria Revuelta, Julio C. Chavez, John L. Reagan, Sonali M. Smith, Ann S. LaCasce, Lei Zhang, Merry Zhai, Chengqing Wu, John P. Leonard, Leandro Cerchietti
Journal: Blood (2017)