tbuckley/cabot-search huggingface dataset:
Players in Drug-Resistant Leukemia Stem/Initiating Cells and Immunity in Patients with CML in Context of Oxygen Levels: Would Collecting/Processing Cells in Hypoxia Offer Additional Information? A Next Frontier of Investigation
Authors: Hal Broxmeyer
Journal: Blood Cancer Discovery (2020)

Abstract Summary: Chronic myelogenous leukemia (CML) is a stem cell disorder once considered an eventual death sentence upon progression to the terminal acute/blastic cell phase, a terrible clinical outcome that has improved with the introduction of tyrosine kinase inhibitors. A major continuing problem with treating CML is the persistence of drug-resistant leukemia stem/initiating cells (LS/IC). In this issue of Blood Cancer Discovery, Silvestri and colleagues describe an incredibly in-depth mechanistic study using genetic and pharmacologic modulation of the miRNA MiR300 with and without treatment with activators of the serine-threonine protein phosphatase 2A (PP2A) in human cells. In vitro studies and in vivo mouse models of patient-derived xenografts were used to address the need to target LS/ICs and restore immunity of impaired natural killer cells for attenuation of CML progression. See related article by Silvestri et al., p. 48.
Pregnancy Stress, Anxiety, and Depression Sequela on Neonatal Brain Development—Reply
Authors: Yao Wu, Catherine Limperopoulos
Journal: JAMA Pediatrics (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 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
Dual oxidase 1 limits the IFNγ-associated antitumor effect of macrophages
Authors: Lydia Meziani, Marine Gerbé de Thoré, Pauline Hamon, Sophie Bockel, Ruy Andrade Louzada, Céline Clemenson, Raphaël Corre, Wincgygn Liu, Corinne Dupuy, Michele Mondini, Eric Deutsch
Journal: Journal for ImmunoTherapy of Cancer (2020)

Macrophages play pivotal roles in tumor progression and the response to anticancer therapies, including radiotherapy (RT). Dual oxidase (DUOX) 1 is a transmembrane enzyme that plays a critical role in oxidant generation. Since we found DUOX1 expression in macrophages from human lung samples exposed to ionizing radiation, we aimed to assess the involvement of DUOX1 in macrophage activation and the role of these macrophages in tumor development. Using Duox1-/- mice, we demonstrated that the lack of DUOX1 in proinflammatory macrophages improved the antitumor effect of these cells. Furthermore, intratumoral injection of Duox1-/- proinflammatory macrophages significantly enhanced the antitumor effect of RT. Mechanistically, DUOX1 deficiency increased the production of proinflammatory cytokines (IFNγ, CXCL9, CCL3 and TNFα) by activated macrophages in vitro and the expression of major histocompatibility complex class II in the membranes of macrophages. We also demonstrated that DUOX1 was involved in the phagocytotic function of macrophages in vitro and in vivo. The antitumor effect of Duox1-/- macrophages was associated with a significant increase in IFNγ production by both lymphoid and myeloid immune cells. Our data indicate that DUOX1 is a new target for macrophage reprogramming and suggest that DUOX1 inhibition in macrophages combined with RT is a new therapeutic strategy for the management of cancers.
Covid-19: Health and care workers will be “highest priority” for vaccination, says JCVI
Authors: Jacqui Wise
Journal: BMJ (2020)

“Frontline” health and social care workers will be the “highest priority for vaccination” once a vaccine against covid-19 becomes available, the UK Joint Committee on Vaccination and Immunisation has said.

The next priority group for vaccination should be people at increased risk of serious disease and death from covid-19 infection according to age and risk factors such as underlying health conditions, says preliminary advice from the JCVI.1 It said work was continuing to identify which groups were most at risk and noted that “early signals have been identified of other potential risk factors including deprivation and ethnicity.”

The advice was developed in response to a request …
Efficacy and safety of topical terbinafine 10% solution (MOB-015) in the treatment of mild to moderate distal subungual onychomycosis: A randomized, multicenter, double-blind, vehicle-controlled phase 3 study
Authors: Aditya K. Gupta, Maria S. Surprenant, Steven E. Kempers, David M. Pariser, Kjell Rensfeldt, Amir Tavakkol
Journal: Journal of the American Academy of Dermatology (2020)
Experiences of liking versus ideas about liking
Authors: Alison Ledgerwood, Paul W. Eastwick, Bertram Gawronski
Journal: Behavioral and Brain Sciences (2020)

Abstract We leverage the notion that abstraction enables prediction to generate novel insights and hypotheses for the literatures on attitudes and mate preferences. We suggest that ideas about liking (e.g., evaluations of categories or overall traits) are more abstract than experiences of liking (e.g., evaluations of particular exemplars), and that ideas about liking may facilitate mental travel beyond the here-and-now.
Abstract B16: Noninvasive liquid biopsies for guideline-compliant diagnostic assessment in ovarian cancers
Authors: Dadasaheb B. Akolkar, Darshana Patil, Revati Patil, Pradip Devhare, Pradip Fulmali, Pooja Fulmali, Shoeb Patel, Navin Srivastava, Vineet Datta, Cynthe Sime, Ajay Srinivasan, Rajan Datar
Journal: Clinical Cancer Research (2020)

Abstract Diagnosis of ovarian adenocarcinomas is based on histopathologic analysis of tumor tissue obtained by invasive biopsies. However, invasive biopsies are associated with procedural expenses, sequelae, and risk of complications. Though immunocytochemistry (ICC) profiling of circulating tumor cells (CTCs, defined as EpCAM+, panCK+, CD45-) has been previously considered for diagnosis in some cancers, the attempts have been unsuccessful. We used a novel approach for enrichment of sufficient viable CTCs that permit meaningful ICC profiling for diagnosis of ovarian cancers in suspected cases. We obtained 15 mL of venous blood draw from 248 patients with confirmed diagnosis of ovarian cancer. PMBCs were isolated by centrifugation. CTCs were enriched from PBMC using an epigenetically acting enrichment process that is lethal towards normal (nonmalignant) cells but confers survival privilege on apoptosis-resistant CTCs. Harvested CTCs were confirmed by immunostaining for EpCAM and pan-CK. Deep ICC profiling of these CTCs was performed with organ-specific markers CA125 and WT1 as well as P63 as a nonspecific marker. Viable CTCs could be obtained from 225 samples (90.7%) out of 248. Among the 100 samples characterized by deep ICC profiling, 70 samples (70%) were positive for CA125 and WT1. None of the samples was positive for P63. Our results show that ICC-based characterization of CTCs can provide necessary diagnostic information noninvasively to substitute conventional procedures dependent on tissue extraction. Citation Format: Dadasaheb B. Akolkar, Darshana Patil, Revati Patil, Pradip Devhare, Pradip Fulmali, Pooja Fulmali, Shoeb Patel, Navin Srivastava, Vineet Datta, Cynthe Sime, Ajay Srinivasan, Rajan Datar. Noninvasive liquid biopsies for guideline-compliant diagnostic assessment in ovarian cancers [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B16.
A modern materialist approach to abstraction, concreteness, and explanation in cognition
Authors: Richard Shillcock
Journal: Behavioral and Brain Sciences (2020)

Abstract Although endorsing the authors’ concentration on the issue of abstraction, I critique (a) the philosophical nature of their abstract–concrete dimension, (b) their view of the brain–world barrier, and (c) their implicit positivist one-way hierarchy that has abstraction as the goal.
Abstract IA12: Response in plasma cfDNA as an early marker of treatment effect in advanced cancer
Authors: Geoffrey R. Oxnard
Journal: Clinical Cancer Research (2020)

Abstract Plasma cfDNA genotyping has been adopted widely as a tool for genotyping of advanced cancer at diagnosis and after treatment resistance. In addition, cfDNA genomics is a highly quantitative biomarker that could be used dynamically to evaluate the effective of a therapy. Our data point to the potential clinical meaning of changes in plasma mutation levels and support specific best practices regarding the clinical integration of this approach. In addition, these data allow us to envision a number of creative clinical applications for cfDNA-based response assessment. Finally, we must evaluate whether existing cfDNA genotyping technologies are well suited to this application, and whether new techniques must be considered in order to meet the practical requirements of a real-time clinical monitoring test. Citation Format: Geoffrey R. Oxnard. Response in plasma cfDNA as an early marker of treatment effect in advanced cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA12.
Creation and Validation of Classification Criteria for Discoid Lupus Erythematosus
Authors: Scott A. Elman, Cara Joyce, Kara Braudis, Benjamin F. Chong, Anthony P. Fernandez, Fukumi Furukawa, Minoru Hasegawa, Hee Joo Kim, Sara J. Li, Christine G. Lian, Jacek C. Szepietowski, Victoria P. Werth, Joseph F. Merola
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Classification criteria are the standardized definitions that are used to enroll uniform cohorts for research studies. They emphasize high specificity and are distinct from diagnostic criteria. No universally recognized classification criteria currently exist for discoid lupus erythematosus (DLE), which has led to problematic heterogeneity in observational and interventional clinical studies across the field. <h3>Objective</h3> To create and validate classification criteria for DLE using 12 previously defined candidate criteria items. <h3>Design, Setting, and Participants</h3> For this diagnostic study, candidate criteria items were prospectively applied by dermatologists and dermatopathologists at clinical visits of patients with DLE or a condition that could be confused for DLE, termed a<i>DLE mimicker</i>, at academic dermatology practices across the United States, Poland, Japan, and South Korea. Data were collected from December 1, 2017, to February 1, 2019, and analyzed from March 1 to September 19, 2019. <h3>Main Outcomes and Measures</h3> Clinical features among these 2 groups were calculated and compared with χ<sup>2</sup>or Fisher exact tests. Candidate models were identified using best subsets logistic regression analysis. Improvement tests, fit statistics, and discrimination were considered to choose a final model. <h3>Results</h3> Nine sites contributed 215 patients, 15 of whom had missing or incomplete data. The final model for DLE classification criteria includes only clinical variables: atrophic scarring (3 points), location in the conchal bowl (2 points), preference for the head and neck (2 points), dyspigmentation (1 point), follicular hyperkeratosis and/or plugging (1 point), and erythematous to violaceous in color (1 point), with an area under the receiving operating characteristic curve of 0.91 (95% CI, 0.87-0.95). A score of at least 5 points yields a sensitivity of 84.1% and a specificity of 75.9% in the classification of DLE, with increasing scores yielding higher specificity. <h3>Conclusions and Relevance</h3> These findings provide the initial validation of classification criteria for DLE for use in observational and clinical trials.
Mortality, Admissions, and Patient Census at SNFs in 3 US Cities During the COVID-19 Pandemic
Authors: Michael L. Barnett, Lissy Hu, Thomas Martin, David C. Grabowski
Journal: JAMA (2020)

This study uses Medicare's Nursing Home Compare and a university long-term care database to compare census, admissions, discharges, and mortality at skilled nursing facilities (SNFs) in 3 metropolitan areas during March-May 2020 vs March-May 2019.
Platelet gene expression and function in patients with COVID-19
Authors: Bhanu Kanth Manne, Frederik Denorme, Elizabeth A. Middleton, Irina Portier, Jesse W. Rowley, Chris Stubben, Aaron C. Petrey, Neal D. Tolley, Li Guo, Mark Cody, Andrew S. Weyrich, Christian C. Yost, Matthew T. Rondina, Robert A. Campbell
Journal: Blood (2020)
In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19
Authors: Xiao-Jing Zhang, Juan-Juan Qin, Xu Cheng, Lijun Shen, Yan-Ci Zhao, Yufeng Yuan, Fang Lei, Ming-Ming Chen, Huilin Yang, Liangjie Bai, Xiaohui Song, Lijin Lin, Meng Xia, Feng Zhou, Jianghua Zhou, Zhi-Gang She, Lihua Zhu, Xinliang Ma, Qingbo Xu, Ping Ye, Guohua Chen, Liming Liu, Weiming Mao, Youqin Yan, Bing Xiao, Zhigang Lu, Gang Peng, Mingyu Liu, Jun Yang, Luyu Yang, Changjiang Zhang, Haofeng Lu, Xigang Xia, Daihong Wang, Xiaofeng Liao, Xiang Wei, Bing-Hong Zhang, Xin Zhang, Juan Yang, Guang-Nian Zhao, Peng Zhang, Peter P. Liu, Rohit Loomba, Yan-Xiao Ji, Jiahong Xia, Yibin Wang, Jingjing Cai, Jiao Guo, Hongliang Li
Journal: Cell Metabolism (2020)
Abstraction: An alternative neurocognitive account of recognition, prediction, and decision making
Authors: Valerie F. Reyna, David A. Broniatowski
Journal: Behavioral and Brain Sciences (2020)

Gilead et al. offer a thoughtful and much-needed treatment of abstraction. However, it fails to build on an extensive literature on abstraction, representational diversity, neurocognition, and psychopathology that provides important constraints and alternative evidence-based conceptions. We draw on conceptions in software engineering, socio-technical systems engineering, and a neurocognitive theory with abstract representations of gist at its core, fuzzy-trace theory.
Patient-reported satisfaction and quality of life after trans male gender affirming surgery
Authors: Colton H. L. McNichols, Devin O'Brien-Coon, Beverly Fischer
Journal: International Journal of Transgender Health (2020)

Background: Trans male gender affirming surgery is becoming more available resulting in an increase in patients undergoing these procedures. There are few reports evaluating the outcomes of these procedures in the transgender population. This study was performed to provide patient-centric insight on self-image and other concerns that arise during surgical transition. Methods: A 22-question survey was sent to 680 trans male patients. The survey was broken down into the following sections: demographics, timing and type of surgical procedures, self-image, sex/dating life, social life, employment, co-existing psychiatric morbidity, and common issues faced during the surgical transition. Results: A total of 246 patients responded (36% response rate). Most patients (54%) waited 1-2 years after starting their transition before having a surgical procedure, and 10% waited longer than 6 years. In regard to self-image, sex/dating life, and social life there was a significant improvement (p < 0.001) after undergoing gender affirming surgery. Patients reported significantly less difficulty with employment after having gender affirming surgery (p < 0.001). If present, the following psychiatric morbidities were self-reported to have a statistically significant improvement after surgery: depression, anxiety, substance abuse, suicidal ideation, panic disorder, social phobia, and obsessive-compulsive disorder (P < 0.003). Conclusion: It is important to provide patients, surgeons, and insurance companies with expected outcomes of gender affirming surgery along with the potential risks and benefits. Post-surgical trans male patients reported a significant improvement in overall quality of life. Initial hesitations to having surgery such as regret and potential complications were found to be non-issues. Additional research should be done to include more patients with phalloplasties, trans females, and nonbinary identifying patients.
Potentiation of the cytotoxicity of pegylated liposomal doxorubicin in cultured tumor cells by chloroquine
Authors: Hilary Shmeeda, Lidia Mak, Dina Tzemach, Alberto Gabizon
Journal: Cancer Research (2007)

2272  A potential problem of liposome-based chemotherapy is the sequestration of liposome-delivered drugs into vesicular (endosomes, lysosomes) acidic compartments following endocytosis of liposomes by tumor cells. Chloroquine (CQ) is a lysosomotropic agent long known to block the acidification of intracellular vesicular compartments. Following endocytosis of doxorubicin (DXR)-containing liposomes and trafficking to endosomes and lysosomes, the drug may be released from liposomes undergoing breakdown but still remain sequestered in intracellular acidic vesicles. We hypothesized that CQ will enhance the transfer of liposomal DXR from acidic vesicles to the cytosol and enhance its efficacy. In this study we examined the effects of CQ (25-100 μM) on the in vitro cytotoxicity of folate targeted (FT) and non-targeted pegylated liposomal DXR (PLD) on a variety of human and mouse tumor cell lines. When CQ was combined with free doxorubicin, no significant enhancement of cytotoxicity was found. In contrast, CQ increased the cytotoxicity of PLD in a variety of cells, as well as that of FT-PLD in cells upregulated for the folate receptor (KB-FR). under continuous 72-hour drug exposure. In short exposure (3 hours) experiments, relative enhancement of FT-PLD cytotoxicity was much more significant than that of PLD. This is consistent with the greater and faster uptake of targeted liposomes by tumor cells, and suggests that CQ acts on the intracellular depot of liposomal drug. CQ was effective when added together with the liposomal drug preparation or after a 3-hour exposure to liposomal drug, but was ineffective when added prior to liposomal drug exposure, a finding consistent with the known ability of CQ to interfere with cell uptake of liposomes. These results demonstrate that CQ can potentiate the in vitro cytotoxic effect of liposomal DXR, and more so that of targeted liposomal DXR, and suggest that CQ can be an attractive agent to enhance the in vivo activity of these formulations.
Bile duct reconstruction with single-operator cholangioscopy and percutaneous radiological rendezvous procedure
Authors: Mohammad Kharbat, Deniz Durmush, Suhrid P. Lodh, Philip I. Craig
Journal: Endoscopy (2020)

Intrahepatic bile leaks secondary to disconnected hepatic segments following liver resection can be difficult to treat [1]. There are only isolated reports of successful endoscopic management [2] [3]. We present the case of a 41-year-old woman with colorectal cancer and hepatic secondaries who received a segment IVb liver resection and multisegment microwave ablation. Surgery was complicated by biliary sepsis and a large biliary leak. Baseline cross-sectional imaging and endoscopic retrograde cholangiopancreatography (ERCP) established the presence of a surgically clipped left hepatic duct and disconnected left lobe leaking into an intrahepatic cavity ([Fig. 1]). Left-sided percutaneous transhepatic biliary drainage (PTBD) was performed and then, under direct cholangioscopic guidance (SpyGlass DS direct visualization system; Boston Scientific, Marlborough, Massachusetts, USA), the occluded left hepatic duct was dilated and the cavity accessed ([Video 1]).
The Clinical impact of PTPN11 mutations in adults with acute myeloid leukemia
Authors: Mansour Alfayez, Ghayas C. Issa, Keyur P. Patel, Feng Wang, Xuemei Wang, Nicholas J. Short, Jorge E. Cortes, Tapan Kadia, Farhad Ravandi, Sherry Pierce, Rita Assi, Guillermo Garcia-Manero, Courtney D. DiNardo, Naval Daver, Naveen Pemmaraju, Hagop Kantarjian, Gautam Borthakur
Journal: Leukemia (2020)
Comprehensive Dual- and Triple-Feature Intersectional Single-Vector Delivery of Diverse Functional Payloads to Cells of Behaving Mammals
Authors: Lief E. Fenno, Charu Ramakrishnan, Yoon Seok Kim, Kathryn E. Evans, Maisie Lo, Sam Vesuna, Masatoshi Inoue, Kathy Y.M. Cheung, Elle Yuen, Nandini Pichamoorthy, Alice S.O. Hong, Karl Deisseroth
Journal: Neuron (2020)
Above and beyond “Above and beyond the concrete”
Authors: Michael Gilead, Yaacov Trope, Nira Liberman
Journal: Behavioral and Brain Sciences (2020)

The commentaries address our view of abstraction, our ontology of abstract entities, and our account of predictive cognition as relying on relatively concrete simulation or relatively abstract theory-based inference. These responses revisit classic questions concerning mental representation and abstraction in the context of current models of predictive cognition. The counter arguments to our article echo: constructivist theories of knowledge, "neat" approaches in artificial intelligence and decision theory, neo-empiricist models of concepts, and externalist views of cognition. We offer several empirical predictions that address points of contention and that highlight the generative potential of our model.
Whole-genome sequence association analysis of blood proteins in a longitudinal wellness cohort
Authors: Wen Zhong, Anders Gummesson, Abdellah Tebani, Max J. Karlsson, Mun-Gwan Hong, Jochen M. Schwenk, Fredrik Edfors, Göran Bergström, Linn Fagerberg, Mathias Uhlén
Journal: Genome Medicine (2020)

The human plasma proteome is important for many biological processes and targets for diagnostics and therapy. It is therefore of great interest to understand the interplay of genetic and environmental factors to determine the specific protein levels in individuals and to gain a deeper insight of the importance of genetic architecture related to the individual variability of plasma levels of proteins during adult life.We have combined whole-genome sequencing, multiplex plasma protein profiling, and extensive clinical phenotyping in a longitudinal 2-year wellness study of 101 healthy individuals with repeated sampling. Analyses of genetic and non-genetic associations related to the variability of blood levels of proteins in these individuals were performed.The analyses showed that each individual has a unique protein profile, and we report on the intra-individual as well as inter-individual variation for 794 plasma proteins. A genome-wide association study (GWAS) using 7.3 million genetic variants identified by whole-genome sequencing revealed 144 independent variants across 107 proteins that showed strong association (P < 6 × 10-11) between genetics and the inter-individual variability on protein levels. Many proteins not reported before were identified (67 out of 107) with individual plasma level affected by genetics. Our longitudinal analysis further demonstrates that these levels are stable during the 2-year study period. The variability of protein profiles as a consequence of environmental factors was also analyzed with focus on the effects of weight loss and infections.We show that the adult blood levels of many proteins are determined at birth by genetics, which is important for efforts aimed to understand the relationship between plasma proteome profiles and human biology and disease.