tbuckley/cabot-search huggingface dataset:
Abstract B38: Impact of nongenetic intratumor heterogeneity on phenotypic characteristics and ongoing evolutionary dynamics in lung tumors
Authors: Anchal Sharma, Elise Merritt, Xiaoju Hu, Angelique Cruz, Jyoti Malhotra, Greogory Riedlinger, Subhajyoti De
Journal: Cancer Research (2020)

Abstract Impacts of genetic and nongenetic intratumor heterogeneity (ITH) on tumor phenotypes and evolvability remain debated. We analyzed ITH in lung squamous cell carcinoma at the levels of genome, transcriptome, tumor-immune interactions, and histopathologic characteristics by multiregion bulk and single-cell sequencing. Genomic heterogeneity alone was a weak indicator of intratumor nongenetic heterogeneity at immune and transcriptomic levels that impacted multiple cancer-related pathways, including those related to proliferation and inflammation, which in turn contributed to intratumor regional differences in histopathology and subtype classification. Tumor subclones had substantial differences in proliferation score, suggestive of non-neutral clonal dynamics. Proliferation and other cancer-related pathways also showed intratumor regional differences, sometimes even within the same subclones. Neoepitope burden negatively correlated with immune infiltration, indicating immune-mediated purifying selection on somatic mutations. Taken together, our observations suggest that nongenetic heterogeneity is a major determinant of heterogeneity in histopathologic characteristics and impacts evolutionary dynamics in lung cancer. Note: This abstract was not presented at the conference. Citation Format: Anchal Sharma, Elise Merritt, Xiaoju Hu, Angelique Cruz, Jyoti Malhotra, Greogory Riedlinger, Subhajyoti De. Impact of nongenetic intratumor heterogeneity on phenotypic characteristics and ongoing evolutionary dynamics in lung tumors [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B38.
Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva
Authors: Sumio Iwasaki, Shinichi Fujisawa, Sho Nakakubo, Keisuke Kamada, Yu Yamashita, Tatsuya Fukumoto, Kaori Sato, Satoshi Oguri, Keisuke Taki, Hajime Senjo, Junichi Sugita, Kasumi Hayasaka, Satoshi Konno, Mutsumi Nishida, Takanori Teshima
Journal: Journal of Infection (2020)
Diet and Acne—Challenges of Translating Nutritional Epidemiologic Research Into Clinical Practice
Authors: John S. Barbieri
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Offline: COVID-19 and the ethics of memory
Authors: Richard Horton
Journal: The Lancet (2020)

Lockdowns are lifting. Lives are returning. And livelihoods are being gradually reclaimed. Very tentatively, societies are beginning to put the pandemic behind them. There are understandable fears of flare-ups. In the UK, several scientists who advise government are warning that ending strict home curfews is premature. There are still about 2000 new cases of infection being diagnosed daily in the UK (the figure in Italy is around 500) and the test, trace, and isolate system remains incomplete. According to WHO, total confirmed cases of COVID-19 are now approaching 6 million globally, with almost 400 000 deaths.
Prospective Staging Evaluation of Patients with Cutaneous T-Cell Lymphomas
Authors: PAUL A. BUNN
Journal: Annals of Internal Medicine (1980)

A prospective pretreatment staging evaluation was done on 49 consecutive patients with mycosis fungoides or the Sézary syndrome to study patterns of disease spread and prognostic factors. Routine staging procedures included complete blood count, blood chemistries, chest roentgenogram, lymphangiogram, radionuclide scans, bone marrow aspiration and biopsy, liver biopsy, and lymph node biopsy. Special evaluations included cytogenetic analysis, electron microscopy, and T-cell cytology. Extracutaneous lymphoma was documented by light microscopy in 51% of patients and by the three special procedures in 88%. Extracutaneous lymphoma was most frequent in blood and lymph nodes; 18% of patients had visceral involvement. Patients with generalized erythroderma had a higher frequency of extracutaneous disease than did patients with cutaneous plaques and tumors by both light microscopy and special studies. Survival was directly related to the type of skin involvement and the presence or absence of extracutaneous disease. Systemic dissemination of cutaneous T-cell lymphoma is frequent, generally asymptomatic, and develops early via the circulation. These findings may explain why cutaneous therapies are associated with a high frequency of relapse.
Chalcone hybrids as potential anticancer agents: Current development, mechanism of action, and structure‐activity relationship
Authors: Feng Gao, Gang Huang, Jiaqi Xiao
Journal: Medicinal Research Reviews (2020)

Abstract The continuous emergency of drug‐resistant cancers and the low specificity of anticancer agents have been the major challenges in the control and treatment of cancer, making an urgent need to develop novel anticancer agents with high efficacy. Chalcones, precursors of flavonoids and isoflavonoids, exhibit structural heterogeneity and can act on various drug targets. Chalcones which demonstrated potential in vitro and in vivo activity against both drug‐susceptible and drug‐resistant cancers, are useful templates for the development of novel anticancer agents. Hybridization of chalcone moiety with other anticancer pharmacophores could provide the hybrids which have the potential to overcome drug resistance and improve the specificity, so it represents a promising strategy to develop novel anticancer agents. This review emphasizes the development, the mechanisms of action as well as structure‐activity relationships of chalcone hybrids with potential therapeutic application for many cancers in recent 10 years.
Current measures are not sufficient: an interview‐based qualitative assessment of quality of life in cutaneous T‐cell lymphoma*
Authors: T.S. Bhat, C.M. Herbosa, A.R. Rosenberg, O. Sogade, D.B. Jeffe, N. Mehta‐Shah, Y.R. Semenov, A.C. Musiek
Journal: British Journal of Dermatology (2020)

Cutaneous T-cell lymphoma (CTCL) negatively impacts quality of life (QoL), but existing QoL questionnaires may not comprehensively reflect patients' experience.To identify the aspects of QoL that are most meaningful to patients with CTCL and to evaluate existing QoL instruments in this context.Semistructured interviews were conducted between May and June 2019 using purposive sampling of patients with CTCL. Data were analysed by an inductive thematic approach using Dedoose Version 8.0.35.One-on-one interviews lasting a median of 43 min were completed by 18 patients [median age 62 years (interquartile range 52-70); 39% advanced-stage (IIB-IV)]. Itch was the most common clinical symptom reported (16 of 18 patients), followed by pain (12 of 18), skin breaks (11 of 18) and skin flaking (10 of 18). Eleven patients reported that their symptoms interfered with sleep, which impacted daily functioning. Patients also noted a lack of understanding of the disease in the community and felt uncertain (12 of 18), depressed (11 of 18), suicidal (four of 18) and hopeless (nine of 18). Nearly all patients (17 of 18) reported a sense of 'otherness' (not feeling 'normal' or 'like themselves'), and most patients (16 of 18) specifically mentioned concern about their physical appearance. Patients also noted substantial treatment burden. Salient patient concerns, including individual clinical symptoms, concern about appearance and problems with sleep, were not adequately or consistently represented in generic, skin-specific or CTCL-specific QoL measures.Incorporating the concerns and priorities that distinguish patients with CTCL from other patient populations will be of paramount importance in developing a comprehensive CTCL-specific measure of QoL that adequately captures patients' experience.
Single-Session Bronchial Thermoplasty Guided by <sup>129</sup>Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial
Authors: Chase S. Hall, James D. Quirk, Charles W. Goss, Daphne Lew, Jim Kozlowski, Robert P. Thomen, Jason C. Woods, Nicholas J. Tustison, John P. Mugler, Lora Gallagher, Tammy Koch, Ken B. Schechtman, Iulian C. Ruset, F. William Hersman, Mario Castro
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Adverse events have limited the use of bronchial thermoplasty (BT) in severe asthma.
Abstract A46: A novel patient-derived approach for preclinical evaluation of predictive imaging biomarkers in early lung cancer
Authors: Eva J. Koziolek, Desiree Martin, Jie Liu, Jorge R. Barrio, W. Dean Wallace, David B. Shackelford, Jane Yanagawa, Steven Dubinett, Claudio Scafoglio
Journal: Cancer Research (2020)

Abstract Background: Lung cancer is the number one cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent type. Lung screening with computed tomography has allowed detection of early nodules that need diagnostic definition. We have identified the sodium-dependent glucose transporter 2 (SGLT2) as a novel diagnostic and therapeutic target that may aid the identification and the treatment of early LUAD. However, a limitation of these studies is the lack of experimental models of early cancer. Patient-derived xenografts (PDXs) are a reliable tool of translational oncology. However, the establishment of PDXs from early-stage, low-grade LUAD is characterized by low efficiency and extremely long experimental times. To study the predictive value of SGLT2 activity in early LUAD, we have established an alternative model based on a double culture system: 1) implantation of tumor tissue on the chorioallantoic membrane (CAM) of the chicken egg (in ovo system), which can be imaged only 1 week after the patient surgery; 2) growth of tumor spheroids in 3D in vitro culture, to test response to treatments. Methods: Each PDX of LUAD is divided in two specimens: one for in ovo growth in the CAM assay and one for the 3D culture as tumor spheroids. The CAM xenografts are imaged with two different tracers to characterize glucose uptake: [18F] fluorodeoxyglucose (FDG), to measure GLUT activity, and 4-[18F] fluorodeoxyglucose (Me4FDG), to assess sodium-dependent glucose transport (SGLT). The PD-tumor spheroids are cultured in 96-well plates and used for treatment with SGLT2 inhibitors as well as other drugs. Results: PET imaging of LUADs with FDG and Me4FDG revealed the presence of both glucose transporters, GLUT1 and SGLT2. Treatment of the tumor spheroids with SGLT2 inhibitors reduced cell viability and caused integrity loss in a dose-dependent manner. Conclusion: The CAM xenograft model is a useful model for implanting PD tumor fragments and studying glucose metabolism in ovo by PET imaging with very short experimental times. Tumor fragments connect to the chicken embryo vasculature within 3-5 days, so that PD material can be analyzed soon after surgery. The Me4FDG uptake in the CAM system predicts the treatment response of tumor spheroids cultured in vitro from the same PD samples. Citation Format: Eva J. Koziolek, Desiree Martin, Jie Liu, Jorge R. Barrio, W. Dean Wallace, David B. Shackelford, Jane Yanagawa, Steven Dubinett, Claudio Scafoglio. A novel patient-derived approach for preclinical evaluation of predictive imaging biomarkers in early lung cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A46.
Sputum neutrophil elastase associates with microbiota and <i>Pseudomonas aeruginosa</i> in bronchiectasis
Authors: Martina Oriano, Andrea Gramegna, Leonardo Terranova, Giovanni Sotgiu, Imran Sulaiman, Luca Ruggiero, Laura Saderi, Benjamin Wu, James D. Chalmers, Leopoldo N. Segal, Paola Marchisio, Francesco Blasi, Stefano Aliberti
Journal: European Respiratory Journal (2020)

Introduction Neutrophilic inflammation is a major driver of bronchiectasis pathophysiology, and neutrophil elastase activity is the most promising biomarker evaluated in sputum to date. How active neutrophil elastase correlates with the lung microbiome in bronchiectasis is still unexplored. We aimed to understand whether active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics. Methods An observational, cross-sectional study was conducted at the bronchiectasis programme of the Policlinico Hospital in Milan, Italy, where adults with bronchiectasis were enrolled between March 2017 and March 2019. Active neutrophil elastase was measured on sputum collected during stable state, microbiota analysed through 16S rRNA gene sequencing, molecular assessment of respiratory pathogens carried out through real-time PCR and clinical data collected. Results Among 185 patients enrolled, decreasing α-diversity, evaluated through the Shannon entropy (ρ −0.37, p&lt;0.00001) and Pielou's evenness (ρ −0.36, p&lt;0.00001) and richness (ρ −0.33, p&lt;0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon entropy as detected between patients with neutrophil elastase ≥20 µg·mL −1 (median 3.82, interquartile range 2.20–4.96) versus neutrophil elastase &lt;20 µg·mL −1 (4.88, 3.68–5.80; p&lt;0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with Pseudomonas in the high-elastase group and with Streptococcus in the low-elastase group. Further confirmation of the association of Pseudomonas aeruginosa with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR. Conclusions High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection.
Predicting the Pathologic Complete Response After Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer
Authors: Marco Bandini, Jeffrey S Ross, Daniele Raggi, Andrea Gallina, Maurizio Colecchia, Roberta Lucianò, Patrizia Giannatempo, Elena Farè, Filippo Pederzoli, Marco Bianchi, Renzo Colombo, Giorgio Gandaglia, Nicola Fossati, Laura Marandino, Umberto Capitanio, Federico Deho’, Siraj M Ali, Russell Madison, Jon H Chung, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Andrea Necchi
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background In the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers. Methods In an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)–combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples. Multivariable logistic regression analyses evaluated baseline clinical T stage and tumor biomarkers in association with pT0N0 response. Corresponding coefficients were used to develop a calculator of pT0N0 response based on the tumor mutational burden (TMB), CPS, and the clinical T stage. Decision-curve analysis was also performed. All statistical tests were 2-sided. Results From February 2017 to June 2019, 112 patients with biomarker data were enrolled (105 with complete TMB and CPS data). Increasing TMB and CPS values featured a linear association with logistic pT0N0 probabilities (P = .02 and P = .004, respectively). For low TMB values (≤11 mut/Mb, median value, n = 53), pT0N0 probability was not associated with increasing CPS. Conversely, for high TMB values (&amp;gt;11 mut/Mb, n = 52), pT0N0 was statistically significantly associated with higher CPS (P = .004). The C index of the pT0N0 probability calculator was 0.77. On decision-curve analysis, the net benefit of the model was higher than the “treat-all” option within the clinically meaningful threshold probabilities of 40%-50%. Conclusions The study presents a composite biomarker-based pT0N0 probability calculator that reveals the complex interplay between TMB and CPS, added to the clinical T stage.
NF‐E2–Related Factor 2 Regulates Interferon Receptor Expression and Alters Macrophage Polarization in Lupus
Authors: Shuhong Han, Haoyang Zhuang, Pui Y. Lee, Mingjia Li, Lijun Yang, Peter A. Nigrovic, Westley H. Reeves
Journal: Arthritis & Rheumatology (2020)

Objective Pristane‐induced lupus is associated with nonresolving inflammation and deficiency of proresolving macrophages. Proresolving nonclassic macrophages ( NCM s) are less responsive to type I interferon ( IFN ) than classic macrophages ( CM s; which are proinflammatory), reflecting their relative expression levels of the type I IFN receptor ( IFNAR ). This study was undertaken to investigate the regulation of IFNAR expression in macrophages. Methods We carried out gene expression profiling of purified CM s and NCM s from mice treated with pristane (which develop lupus) or mineral oil (non‐lupus controls). Macrophage differentiation and IFNAR expression were examined in mice treated with NF ‐E2–related factor 2 (Nrf2) activators and inhibitors and in Nrf2‐deficient mice. Nrf2 activity was also assessed in blood cells from patients with systemic lupus erythematosus ( SLE ). Significant differences were determined by Student's t ‐test. Results RNA sequencing revealed increased expression of genes regulated by the transcription factor Nrf2 in NCM s from mineral oil–treated versus pristane‐treated mice and in NCM s versus CM s. The Nrf2 activator CDDO ‐imidazole ( CDDO ‐Im) decreased CM s ( P &lt; 0.0001) and promoted the development of proresolving NCM s ( P = 0.06), whereas the Nrf2 inhibitor brusatol increased CM s ( P &lt; 0.05) and decreased NCM s ( P &lt; 0.001). CDDO ‐Im decreased Ifnar1 ( P &lt; 0.001) and IFN ‐stimulated gene ( ISG ) expression in macrophages and alleviated oxidative stress ( P &lt; 0.05), whereas brusatol had the opposite effect ( P &lt; 0.01). Moreover, Ifnar1 and ISG expression levels were higher in Nrf2‐knockout mice than controls ( P &lt; 0.05). As seen in mice with lupus, SLE patients showed evidence of low Nrf2 activity. Conclusion Our findings indicate that Nrf2 activation favors the resolution of chronic inflammation in lupus. Since autoantibody production and lupus nephritis depend on IFNAR signaling, the ability of Nrf2 activators to repolarize macrophages and reduce the INF signature suggests that these agents may warrant consideration for treating lupus.
A bubble bursting-mediated oral drug delivery system that enables concurrent delivery of lipophilic and hydrophilic chemotherapeutics for treating pancreatic tumors in rats
Authors: Kuan-Hung Chen, Yang-Bao Miao, Chun-Yu Shang, Tring-Yo Huang, Yu-Tzu Yu, Chun-Nan Yeh, Hsiang-Lin Song, Chiung-Tong Chen, Fwu-Long Mi, Kun-Ju Lin, Hsing-Wen Sung
Journal: Biomaterials (2020)
THU0463 EFFICACY AND SAFETY OF NERIDRONATE IN BONE EDEMA SYNDROME
Authors: A. M. Lurati, A. Laria, P. Faggioli, L. Castelnovo, A. Tamburello, A. Mazzone
Journal: Annals of the Rheumatic Diseases (2020)

Background: Bone Marrow Edema Syndrome (BMES) is a severely disabling pain syndrome without a definite treatment and refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). Magnetic resonance imaging is used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment. Objectives: Aim of this monocentric trial was to test the efficacy and the safety of the amino-bisphosphonate neridronate in patients with BMES administered in two different regimens. Methods: 192 patients with BMES secondary to osteoarthritis localized to knee, hip, wrist or foot were randomly assigned to I.V. infusion of 100 mg neridronate given four times over 10 days (Group A, 72 subjects) or alternatively to I.V. infusions of 100 mg every 21 days over 3 months (Group B, 120 subjects). At baseline and after 180 days we performed an MRI. We assessed a 0-100 mm pain VAS in each patient, too. Outcomes were to evaluate the MRI changes and the VAS changes. A control group (35 patients) was enrolled too, treated conservatively with NSAIDs and articular rest. Results: we observed a significant improvement in MRI with the resolution of bone marrow lesions present at the baseline (p&lt;0.01), without a significant difference between Group A and Group B. Visual analogue scale (VAS) score decreased significantly during the study in both groups (p&lt;0.05) without a significant difference between the two treatment groups (p&gt;0.1). Both groups showed a significant clinical and radiologic improvement compared with control group (p&lt;0.001). Conclusion: In patients with BMES, the infusions of neridronate 100 mg every 21 days over 3 months or alternately every 3 days over 10 days are associated with clinically relevant and persistent benefits without significant differences between the two treatment-schedules. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice BMES. Disclosure of Interests: : None declared