tbuckley/cabot-search huggingface dataset:
Sensing Inflammation Biomarkers with Electrolyte‐Gated Organic Electronic Transistors
Authors: Bernhard Burtscher, Pamela Allison Manco Urbina, Chiara Diacci, Simone Borghi, Marcello Pinti, Andrea Cossarizza, Carlo Salvarani, Magnus Berggren, Fabio Biscarini, Daniel T. Simon, Carlo A. Bortolotti
Journal: Advanced Healthcare Materials (2021)

Abstract An overview of cytokine biosensing is provided, with a focus on the opportunities provided by organic electronic platforms for monitoring these inflammation biomarkers which manifest at ultralow concentration levels in physiopathological conditions. Specifically, two of the field's state‐of‐the‐art technologies—organic electrochemical transistors (OECTs) and electrolyte gated organic field effect transistors (EGOFETs)—and their use in sensing cytokines and other proteins associated with inflammation are a particular focus. The overview will include an introduction to current clinical and “gold standard” quantification techniques and their limitations in terms of cost, time, and required infrastructure. A critical review of recent progress with OECT‐ and EGOFET‐based protein biosensors is presented, alongside a discussion onthe future of these technologies in the years and decades ahead. This is especially timely as the world grapples with limited healthcare diagnostics during the Coronavirus disease (COVID‐19)pandemic where one of the worst‐case scenarios for patients is the “cytokine storm.” Clearly, low‐cost point‐of‐care technologies provided by OECTs and EGOFETs can ease the global burden on healthcare systems and support professionals by providing unprecedented wealth of data that can help to monitor disease progression in real time.
Reports of anaphylaxis after coronavirus disease 2019 vaccination, South Korea, 26 February to 30 April 2021
Authors: Eunju Lee, Yeon-kyeong Lee, Tae Eun Kim, Insob Hwang, Yeon Haw Jung, Hye Ryeon Lee, Jeongsuk Song, Youngjoon Park, Enhi Cho, Yeon-Kyeng Lee
Journal: Eurosurveillance (2021)

The South Korea mass vaccination programme administered 3.8 million doses of COVID-19 vaccinations between 26 February and 30 April 2021. After 173 suspected anaphylaxis reports to the nationwide monitoring system for adverse events following immunisation, 44 anaphylaxis cases were confirmed using Brighton Collaboration case definitions. The rates per million doses were 18.2 cases and 6.2 cases for Vaxzevria and Comirnaty, respectively. Median time of onset was 14 min after vaccination and most cases had recovered at the time of review.
Effect of Diet Quality and Genetic Predisposition on Hemoglobin A1c and Type 2 Diabetes Risk: Gene-Diet Interaction Analysis of 357,419 Individuals
Authors: Pan Zhuang, Xiaohui Liu, Yin Li, Xuzhi Wan, Yuqi Wu, Fei Wu, Yu Zhang, Jingjing Jiao
Journal: Diabetes Care (2021)

OBJECTIVE To assess the interactions between diet quality and genetic predisposition to incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Between 2006 and 2010, 357,419 participants with genetic and complete dietary data from the UK Biobank were enrolled and prospectively followed up to 2017. The genetic risk score (GRS) was calculated on the basis of 424 variants associated with T2D risk, and a higher GRS indicates a higher genetic predisposition to T2D. The adherence to a healthy diet was assessed by a diet quality score comprising 10 important dietary components, with a higher score representing a higher overall diet quality. RESULTS There were 5,663 incident T2D cases documented during an average of 8.1 years of follow-up. A significant negative interaction was observed between the GRS and the diet quality score. After adjusting for major risk factors, per SD increment in the GRS and the diet quality score was associated with a 54% higher and a 9% lower risk of T2D, respectively. A simultaneous increment of 1 SD in both the diet quality score and GRS was additionally associated with a 3% lower T2D risk due to the antagonistic interaction. In categorical analyses, a sharp reduction of 23% in T2D risk associated with a 1-SD increment in the diet quality score was detected among participants in the extremely high GRS group (GRS &amp;gt;95%). We also observed a strong negative interaction between the GRS and the diet quality score on the blood HbA1c level at baseline (P &amp;lt; 0.001). CONCLUSIONS The adherence to a healthy diet was associated with more reductions in blood HbA1c levels and subsequent T2D risk among individuals with a higher genetic risk. Our findings support tailoring dietary recommendations to an individual’s genetic makeup for T2D prevention.
Chemotherapeutic agents as radiation sensitizers.
Authors: Theodore S. Lawrence
Journal: Cancer Research (2004)

It is not an exaggeration to state that most of the advances in curing cancer in the last decade have come from successful combinations of conventional chemotherapeutic agents with radiation therapy. Further improvements in therapy will depend on understanding the mechanisms by which chemotherapy improves the effectiveness of radiation in model systems and in patients. In this talk, I will discuss the mechanisms of radiosensitization of the fluoropyrimidines, gemcitabine, and the platinums. The fluoropyrimidines (5-fluorouracil and fluorodeoxyuridine) and gemcitabine increase the effectiveness of radiation chiefly when given before and during radiation. Increased radiation sensitivity occurs in cells that progress inappropriately into early phase S in the presence of drug. In the case of gemcitabine, investigations have focused on the roles of specific DNA repair pathways, such as homologous recombination and mismatch repair, as well as the affect of drug on the apoptotic threshold. The dysregulation of cell cycle check points in cancer cells may provide the molecular basis for selective sensitization of tumors compared to normal tissues. Cisplatin has multiple effects on cells, such as adduct formation and DNA damage repair inhibition, but the mechanism for selectivity against cancer cells compared to normal cells is not yet determined. The identification of the enzymatic targets for these drugs offers the potential to develop predictive assays for response and to develop methods of imaging the progress of therapy. Supported by RO1 CA78554
Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus
Authors: Silva Kasela, Zharko Daniloski, Sailalitha Bollepalli, Tristan X. Jordan, Benjamin R. tenOever, Neville E. Sanjana, Tuuli Lappalainen
Journal: Genome biology (2021)

Abstract To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.
Longitudinal analyses of CLL in mice identify leukemia-related clonal changes including a Myc gain predicting poor outcome in patients
Authors: Selcen Öztürk, Yashna Paul, Saira Afzal, Irene Gil-Farina, Anna Jauch, Peter-Martin Bruch, Verena Kalter, Bola Hanna, Lavinia Arseni, Philipp M. Roessner, Manfred Schmidt, Stephan Stilgenbauer, Sascha Dietrich, Peter Lichter, Marc Zapatka, Martina Seiffert
Journal: Leukemia (2021)

Abstract Chronic lymphocytic leukemia (CLL) is a B-cell malignancy mainly occurring at an advanced age with no single major genetic driver. Transgenic expression of TCL1 in B cells leads after a long latency to a CLL-like disease in aged Eµ- TCL1 mice suggesting that TCL1 overexpression is not sufficient for full leukemic transformation. In search for secondary genetic events and to elucidate the clonal evolution of CLL, we performed whole exome and B-cell receptor sequencing of longitudinal leukemia samples of Eµ- TCL1 mice. We observed a B-cell receptor stereotypy, as described in patients, confirming that CLL is an antigen-driven disease. Deep sequencing showed that leukemia in Eµ- TCL1 mice is mostly monoclonal. Rare oligoclonality was associated with inability of tumors to develop disease upon adoptive transfer in mice. In addition, we identified clonal changes and a sequential acquisition of mutations with known relevance in CLL, which highlights the genetic similarities and therefore, suitability of the Eµ- TCL1 mouse model for progressive CLL. Among them, a recurrent gain of chromosome 15, where Myc is located, was identified in almost all tumors in Eµ- TCL1 mice. Interestingly, amplification of 8q24, the chromosomal region containing MYC in humans, was associated with worse outcome of patients with CLL.
25995 5-year efficacy of tildrakizumab 100 and 200 mg by PASI 50/75/90/100 and PGA in reSURFACE 1
Authors: Andrew Blauvelt, Rodney Sinclair, Akihiko Asahina, Atsuyuki Igarashi, Alan M. Mendelsohn, Stephen J. Rozzo, Kimberly Eads, Scott Guenthner, Lyn Guenther
Journal: Journal of the American Academy of Dermatology (2021)
閉塞性肥大型心筋症様の血行動態を呈した「たこつぼ心筋症」の1例
Authors: 舌間夢, 田中信英, 佐藤真司, 仲吉孝晴, 杉原充, 清水知彦, 井上寛子, 池田次郎, 森井誠士, 麻生明見, 森隆宏, 木村好邦, 横山晋二, 森超夫, 中村俊博, 冷牟田浩司
Journal: Circulation (2008)
Anti-proliferative activity of the mTOR inhibitor deforolimus (AP23573; MK-8669) in combination with cytotoxic and targeted agents in sarcoma and endometrial cancer models
Authors: Rachel Squillace, David Miller, Tim Clackson, Victor Rivera
Journal: Cancer Research (2008)

4006  Deforolimus is a potent, non-prodrug analog of rapamycin that inhibits mTOR, a downstream effector of the PI3K/Akt and nutrient sensing pathways. Inhibition of mTOR signaling creates a starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and angiogenesis. As a single agent, deforolimus has shown broad potential as a cancer therapy and has already demonstrated activity in patients with metastatic sarcoma and endometrial cancer, two indications for which few therapeutic options are available. The favorable safety profile of deforolimus and the frequent dysregulation of the mTOR signaling pathway in cancers suggest the potential for deforolimus to be effectively combined with other chemotherapeutic and targeted agents. The goal of this study was to evaluate the combined activity of deforolimus with agents that are typically used to treat sarcoma and endometrial cancers and with agents for which there is a mechanistic rationale for combined use. Sarcoma and endometrial cancer cell lines were treated in vitro with combinations of drugs for 3 days. Data were analyzed by the Median Effect method to determine whether the combination had antagonistic, additive or synergistic activity. In 4 sarcoma cell lines tested, the combination of deforolimus and doxorubicin was found to have additive (VAESBJ, Sk-LMS-1 and Saos-2) or modest synergistic (U2OS) activity. In all 3 endometrial cell lines tested (RL95.2, AN3CA, HEC-1B), the combination of deforolimus with either doxorubicin, carboplatin or paclitaxel showed additive activity, as did the triple combination of carboplatin, paclitaxel and deforolimus. Since a hallmark of cancer cells is increased levels of glycolysis and mTOR plays an important role in regulating nutrient metabolism the activity of deforolimus was examined in combination with the metabolic inhibitor, 2-deoxyglucose. With this combination, additive growth inhibition was observed for all sarcoma and endometrial lines tested. Finally, the activity of deforolimus was examined in combination with 17-desmethoxy-17-N,N-dimethylaminoethylamino-geldanamycin (17-DMAG), a specific inhibitor of the Hsp90 chaperone protein. Hsp90 is required for the expression of a myriad of client oncoproteins including Akt. Interestingly, the combination of deforolimus and 17-DMAG was synergistic in 2 of 4 sarcoma and 1 of 3 endometrial lines, with additive effects observed in the other lines. Pre- and post-treatment levels of key signaling proteins are being examined in an effort to identify molecular correlates of synergistic activity. These results provide preclinical support for the testing of deforolimus in combination with agents typically used to treat sarcoma and endometrial cancer patients and suggest additional combinations worthy of further exploration preclinically.
Clonal Hematopoiesis: From Mechanisms to Clinical Intervention
Authors: Thomas Köhnke, Ravindra Majeti
Journal: Cancer Discovery (2021)

Our knowledge of how clonal hematopoiesis relates to diverse health conditions has grown vastly over the past years, touching upon many specialties beyond cancer medicine. Given that clonal hematopoiesis can act as a precursor to overt disease in many settings, the promise of early intervention has garnered much attention. In this review, we discuss the state of clonal hematopoiesis research and outline the challenges in developing clinical trials of early interventions. We anticipate that incidental findings of clonal hematopoiesis will become more common in the near future, but evidence-based efforts of how to manage these findings is currently lacking. Our knowledge regarding the relevance of clonal hematopoiesis has increased drastically over the past years. However, evidence of how to manage these findings is currently lacking. In this review, we summarize the current state of clonal hematopoiesis research and outline the challenges of developing clinical trials in this field. We anticipate that incidental findings of clonal hematopoiesis will become more common in the near future and argue that there is urgency to start designing and conducting prospective trials.
Effect of Exercise, Escitalopram, or Placebo on Anxiety in Patients With Coronary Heart Disease
Authors: James A. Blumenthal, Patrick J. Smith, Wei Jiang, Alan Hinderliter, Lana L. Watkins, Benson M. Hoffman, William E. Kraus, Lawrence Liao, Jonathan Davidson, Andrew Sherwood
Journal: JAMA Psychiatry (2021)

Anxiety is common among patients with coronary heart disease (CHD) and is associated with worse health outcomes; however, effective treatment for anxiety in patients with CHD is uncertain.To determine whether exercise and escitalopram are better than placebo in reducing symptoms of anxiety as measured by the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) and in improving CHD risk biomarkers.This randomized clinical trial was conducted between January 2016 and May 2020 in a tertiary care teaching hospital in the US and included 128 outpatients with stable CHD and a diagnosed anxiety disorder or a HADS-A score of 8 or higher who were older than 40 years, sedentary, and not currently receiving mental health treatment.Twelve weeks of aerobic exercise 3 times per week at an intensity of 70% to 85% heart rate reserve, escitalopram (up to 20 mg per day), or placebo pill equivalent.The primary outcome was HADS-A score. CHD biomarkers included heart rate variability, baroreflex sensitivity, and flow-mediated dilation, along with 24-hour urinary catecholamines.The study included 128 participants. The mean (SD) age was 64.6 (9.6) years, and 37 participants (29%) were women. Participants randomized to the exercise group and escitalopram group reported greater reductions in HADS-A (exercise, -4.0; 95% CI, -4.7 to -3.2; escitalopram, -5.7; 95% CI, -6.4 to -5.0) compared with those randomized to placebo (-3.5; 95% CI, -4.5 to -2.4; P = .03); participants randomized to escitalopram reported less anxiety compared with those randomized to exercise (-1.67; 95% CI, -2.68 to -0.66; P = .002). Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; 95% CI, -0.2 to 0.3; escitalopram z score = -0.24; 95% CI, -0.4 to 0; placebo z score = 0.36; 95% CI, 0 to 0.7), with greater reductions in the exercise group and escitalopram group compared with the placebo group (F1,127 = 4.93; P = .01) and greater reductions in the escitalopram group compared with the exercise group (F1,127 = 4.37; P = .04). All groups achieved comparable but small changes in CHD biomarkers, with no differences between treatment groups.Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD. However, the beneficial effects of exercise on anxiety symptoms were less consistent. Exercise and escitalopram did not improve CHD biomarkers of risk, which should prompt further investigation of these interventions on clinical outcomes in patients with anxiety and CHD.ClinicalTrials.gov Identifier: NCT02516332.
Traitement des fractures et luxations des membres.
Journal: JAMA (1925)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
26718 Comparison of long-term treatment patterns between ixekizumab and secukinumab users among biologic-experienced psoriasis patients
Authors: Andrew Blauvelt, Nianwen Shi, Russel Burge, Terri L. Ridenour, Najwa Somani, Baojin Zhu, Bilal Atiya, Carolyn R. Lew, Scott A. Kern, Nicole M. Zimmerman, Mwangi J. Murage
Journal: Journal of the American Academy of Dermatology (2021)
Out-of-Pocket Costs of Diagnostic Breast Imaging Services After Screening Mammography Among Commercially Insured Women From 2010 to 2017
Authors: Kathryn P. Lowry, Sarah Bell, A. Mark Fendrick, Ruth C. Carlos
Journal: JAMA Network Open (2021)

This cross-sectional study evaluates the out-of-pocket costs of diagnostic breast imaging services incurred by commercially insured women who underwent additional imaging evaluation and procedures after screening mammography.
Utilizing a Biology-Driven Approach to Map the Exposome in Health and Disease: An Essential Investment to Drive the Next Generation of Environmental Discovery
Authors: Ming Kei Chung, Stephen M. Rappaport, Craig E. Wheelock, Vy Kim Nguyen, Thomas P. van der Meer, Gary W. Miller, Roel Vermeulen, Chirag J. Patel
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Recent developments in technologies have offered opportunities to measure the exposome with unprecedented accuracy and scale.However, because most investigations have targeted only a few exposures at a time, it is hypothesized that the majority of the environmental determinants of chronic diseases remain unknown.OBJECTIVES: We describe a functional exposome concept and explain how it can leverage existing bioassays and high-resolution mass spectrometry for exploratory study.We discuss how such an approach can address well-known barriers to interpret exposures and present a vision of nextgeneration exposomics.DISCUSSION: The exposome is vast.Instead of trying to capture all exposures, we can reduce the complexity by measuring the functional exposomethe totality of the biologically active exposures relevant to disease development-through coupling biochemical receptor-binding assays with affinity purification-mass spectrometry.We claim the idea of capturing exposures with functional biomolecules opens new opportunities to solve critical problems in exposomics, including low-dose detection, unknown annotations, and complex mixtures of exposures.Although novel, biology-based measurement can make use of the existing data processing and bioinformatics pipelines.The functional exposome concept also complements conventional targeted and untargeted approaches for understanding exposure-disease relationships.CONCLUSIONS: Although measurement technology has advanced, critical technological, analytical, and inferential barriers impede the detection of many environmental exposures relevant to chronic-disease etiology.Through biology-driven exposomics, it is possible to simultaneously scale up discovery of these causal environmental factors.
27237 Effect of abrocitinib vs dupilumab and placebo on patient-reported outcomes (PROs) in moderate-to-severe atopic dermatitis (AD) in JADE COMPARE
Authors: Gil Yosipovitch, Jacob P. Thyssen, Carle Paul, Shawn G. Kwatra, Chia-Yu Chu, Ricardo Rojo, Hernan Valdez, Claire Feeney, Fan Zhang, Daniela E. Myers, Marco DiBonaventura
Journal: Journal of the American Academy of Dermatology (2021)
DS26: COVID‐19 and reduced detection of malignant melanoma in secondary dermatology services
Journal: British Journal of Dermatology (2021)

time (DTT; target 31 days) and the urgent referral to first definitive treatment time (TWWt; target 62 days).The secondary outcome measures included SCC severity (macroscopic diameter, tumour thickness, perineural or lymphovascular invasion, tumour stage) and MM severity (Breslow thickness, tumour stage).In total, 77 cases were analysed from 2019 and 78 from 2020; differences were explored using the N -1 v 2 -test.The number of referrals meeting the target TWWa (75% vs. 44%; P < 0Á001), DTT (56% vs. 40%; P < 0Á05) and TWWt (63% vs. 35%; P = 0Á02) was higher in all categories in our 2019 cohort.We also saw a tendency for tumours associated with a worse prognosis during the pandemic, e.g. a mean MM Breslow thickness of 1Á98 mm vs. 1Á36 mm.Our results reflect the detrimental impact of the pandemic on our ability to deliver timely cancer care.Our data were limited by the small number of patients and provide a preliminary insight into the impact of the COVID-19 pandemic on skin cancer services.The impact on tumour severity, recurrence rates, quality of life and mental health of our patients requires further analysis in order to plan for future health crises.
Recovery of Deleted Deep Sequencing Data Sheds More Light on the Early Wuhan SARS-CoV-2 Epidemic
Authors: Jesse D Bloom
Journal: Molecular Biology and Evolution (2021)

The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH's Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2's bat coronavirus relatives.