tbuckley/cabot-search huggingface dataset:
Use of Flow Cytometry to Evaluate the Immunophenotypic Profile of Patients with Chronic Lymphocytic Leukemia from Rio Grande Do Norte State, Brazil
Authors: Aldair Paiva, Gabriela Va Alves, Lorena Kf Silva, Daniela Gb Albuquerque, Francisco F Nascimento, Rodrigo Villar Freitas, Dany Gkc Silva, Marcelo Rocha Barbosa, Geraldo Barroso Cavalcanti
Journal: Blood (2017)
Ultra-deep next-generation sequencing of plasma cell-free DNA in patients with advanced lung cancers: results from the Actionable Genome Consortium
Authors: B.T. Li, F. Janku, B. Jung, C. Hou, K. Madwani, R. Alden, P. Razavi, J.S. Reis-Filho, R. Shen, J.M. Isbell, A.W. Blocker, N. Eattock, S. Gnerre, R.V. Satya, H. Xu, C. Zhao, M.P. Hall, Y. Hu, A.J. Sehnert, D. Brown, M. Ladanyi, C.M. Rudin, N. Hunkapiller, N. Feeney, G.B. Mills, C.P. Paweletz, P.A. Janne, D.B. Solit, G.J. Riely, A. Aravanis, G.R. Oxnard
Journal: Annals of Oncology (2019)

BackgroundNoninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients while also elucidating disease heterogeneity. We sought to develop an ultra-deep plasma next-generation sequencing (NGS) assay for patients with non-small-cell lung cancers (NSCLC) that could detect targetable oncogenic drivers and resistance mutations in patients where tissue biopsy failed to identify an actionable alteration.Patients and methodsPlasma was prospectively collected from patients with advanced, progressive NSCLC. We carried out ultra-deep NGS using cfDNA extracted from plasma and matched white blood cells using a hybrid capture panel covering 37 lung cancer-related genes sequenced to 50000× raw target coverage filtering somatic mutations attributable to clonal hematopoiesis. Clinical sensitivity and specificity for plasma detection of known oncogenic drivers were calculated and compared with tissue genotyping results. Orthogonal ddPCR validation was carried out in a subset of cases.ResultsIn 127 assessable patients, plasma NGS detected driver mutations with variant allele fractions ranging from 0.14% to 52%. Plasma ddPCR for EGFR or KRAS mutations revealed findings nearly identical to those of plasma NGS in 21 of 22 patients, with high concordance of variant allele fraction (r = 0.98). Blinded to tissue genotype, plasma NGS sensitivity for de novo plasma detection of known oncogenic drivers was 75% (68/91). Specificity of plasma NGS in those who were driver-negative by tissue NGS was 100% (19/19). In 17 patients with tumor tissue deemed insufficient for genotyping, plasma NGS identified four KRAS mutations. In 23 EGFR mutant cases with acquired resistance to targeted therapy, plasma NGS detected potential resistance mechanisms, including EGFR T790M and C797S mutations and ERBB2 amplification.ConclusionsUltra-deep plasma NGS with clonal hematopoiesis filtering resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsy was inadequate for genotyping.
Whistleblowers: promises of protection are repeatedly broken, meeting hears
Authors: Clare Dyer
Journal: BMJ (2019)

There has never been a more dangerous time for frontline NHS staff to consider speaking up in defence of patients, a consultant surgeon who lost his job after reporting concerns about an avoidable death has told a meeting on whistleblowing at the Royal Society of Medicine.

All three levels of supposed protection—the NHS itself, regulators, and the law—are failing whistleblowers, Peter Duffy said.

Duffy, who reported his worries to the Care Quality Commission in 2015, won his case for unfair constructive dismissal at an employment tribunal last July. He was awarded £102 000 (€120 000; $135 000), which related to a dispute over pay, not his disclosures.

He told the meeting, opened by the RSM’s president, Simon Wessely, that he had been forced to resign from University Hospitals of …
Rationale and design of the DIGIT‐HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double‐blind, placebo‐controlled study
Authors: Udo Bavendiek, Dominik Berliner, Lukas Aguirre Dávila, Johannes Schwab, Lars Maier, Sebastian A. Philipp, Andreas Rieth, Ralf Westenfeld, Christopher Piorkowski, Kristina Weber, Anja Hänselmann, Maximiliane Oldhafer, Sven Schallhorn, Heiko von der Leyen, Christoph Schröder, Christian Veltmann, Stefan Störk, Michael Böhm, Armin Koch, Johann Bauersachs
Journal: European Journal of Heart Failure (2019)

Despite recent advances in the treatment of chronic heart failure (HF), mortality and hospitalizations still remain high. Additional therapies to improve mortality and morbidity are urgently needed. The efficacy of cardiac glycosides - although regularly used for HF treatment - remains unclear. DIGIT-HF was designed to demonstrate that digitoxin on top of standard of care treatment improves mortality and morbidity in patients with HF and a reduced ejection fraction (HFrEF).
Foraging extends beyond food: Hoarding of mental energy and information seeking in response to uncertainty
Authors: Jessica L. Alquist, Roy F. Baumeister
Journal: Behavioral and Brain Sciences (2019)

When an environment is uncertain, humans and other animals benefit from preparing for and attempting to predict potential outcomes. People respond to uncertainty both by conserving mental energy on tasks unrelated to the source of the uncertainty and by increasing their attentiveness to information related to the uncertainty. This mental hoarding and foraging allow people to prepare in uncertain situations.
Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics
Authors: Xiaojun Feng, Antoni Sureda, Samineh Jafari, Zahra Memariani, Devesh Tewari, Giuseppe Annunziata, Luigi Barrea, Sherif T.S. Hassan, Karel Šmejkal, Milan Malaník, Alice Sychrová, Davide Barreca, Lovro Ziberna, Mohamad Fawzi Mahomoodally, Gokhan Zengin, Suowen Xu, Seyed Mohammad Nabavi, Ai-Zong Shen
Journal: Theranostics (2019)

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.
Citrullination in Cancer
Authors: Arseniy E. Yuzhalin
Journal: Cancer Research (2019)

Abstract Posttranslational modifications of proteins have been implicated in pathogenesis of numerous diseases. Arginine deimination (also known as citrullination) has a principal role in progression of rheumatoid arthritis through generation of autoantibodies and exacerbation of the inflammatory response. Recently, multiple research groups provided solid evidence of citrullination being in control of cancer progression; however, there is no comprehensive overview of these findings. This article summarizes and critically reviews the influence of citrullination on different aspects of tumor biology, including (i) regulation of apoptosis and differentiation, (ii) promoting EMT and metastasis, and (iii) potential use of citrullinated antigens for immunotherapy. In addition, (iv) the role of citrullination as a cancer biomarker and (v) implication of neutrophil extracellular traps in tumorigenesis are discussed. In summary, current findings testify to the significance of arginine deimination in tumor biology and thus more basic and translational studies are needed to further explore this topic.
The Need to Better Define the Who, What, and Where of Resuscitative Endovascular Balloon Occlusion of the Aorta
Authors: Gilbert R. Upchurch, R. Stephen Smith
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
Focusing on CAMHS ignores prevention through public health funding
Authors: Lukasz Kowalewski, Eleanor Hind, Beata Kowalewska
Journal: BMJ (2019)

The BMJ highlights the lack of mental health services available to general practitioners faced with a young person with mental health difficulties.1 The clinical reality of this is supported by the declining numbers of mental health professionals.2 Despite repeated promises by this government, additional funding does not seem to be reaching frontline services.3

Focusing too heavily on provision …
In-Hospital Cardiac Arrest
Authors: Lars W. Andersen, Mathias J. Holmberg, Katherine M. Berg, Michael W. Donnino, Asger Granfeldt
Journal: JAMA (2019)

<h3>Importance</h3> In-hospital cardiac arrest is common and associated with a high mortality rate. Despite this, in-hospital cardiac arrest has received little attention compared with other high-risk cardiovascular conditions, such as stroke, myocardial infarction, and out-of-hospital cardiac arrest. <h3>Observations</h3> In-hospital cardiac arrest occurs in over 290 000 adults each year in the United States. Cohort data from the United States indicate that the mean age of patients with in-hospital cardiac arrest is 66 years, 58% are men, and the presenting rhythm is most often (81%) nonshockable (ie, asystole or pulseless electrical activity). The cause of the cardiac arrest is most often cardiac (50%-60%), followed by respiratory insufficiency (15%-40%). Efforts to prevent in-hospital cardiac arrest require both a system for identifying deteriorating patients and an appropriate interventional response (eg, rapid response teams). The key elements of treatment during cardiac arrest include chest compressions, ventilation, early defibrillation, when applicable, and immediate attention to potentially reversible causes, such as hyperkalemia or hypoxia. There is limited evidence to support more advanced treatments. Post–cardiac arrest care is focused on identification and treatment of the underlying cause, hemodynamic and respiratory support, and potentially employing neuroprotective strategies (eg, targeted temperature management). Although multiple individual factors are associated with outcomes (eg, age, initial rhythm, duration of the cardiac arrest), a multifaceted approach considering both potential for neurological recovery and ongoing multiorgan failure is warranted for prognostication and clinical decision-making in the post–cardiac arrest period. Withdrawal of care in the absence of definite prognostic signs both during and after cardiac arrest should be avoided. Hospitals are encouraged to participate in national quality-improvement initiatives. <h3>Conclusions and Relevance</h3> An estimated 290 000 in-hospital cardiac arrests occur each year in the United States. However, there is limited evidence to support clinical decision making. An increased awareness with regard to optimizing clinical care and new research might improve outcomes.
Renal denervation achieves sustained blood pressure reduction, finds trial
Authors: Susan Mayor
Journal: BMJ (2019)

Endovascular ultrasound renal denervation, a one-off procedure targeting the nerves in the renal arteries, maintains lower blood pressure (BP) in patients with moderate hypertension at six months compared with patients given a sham procedure, a randomised trial has shown.1

“If long term safety and efficacy is proven in larger trials that are currently underway, we hope that renal denervation therapy could soon be offered as an alternative to many lifelong drugs for hypertension,” said the principal investigator in the UK, Melvin Lobo from Queen Mary University of London …
Does the “incentive hope” hypothesis explain food-wasting behavior among humans? Yes and no
Authors: Michał Misiak, Piotr Sorokowski, Maciej Karwowski
Journal: Behavioral and Brain Sciences (2019)

In this commentary, we discuss how the “incentive hope” hypothesis explains differences in food-wasting behaviors among humans. We stress that the role of relevant ecological characteristics should be taken into consideration together with the incentive hope hypothesis: population mobility, animal domestication, and food-wasting visibility.
Retraction: p53 Regulates Cellular Resistance to Complement Lysis through Enhanced Expression of CD59
Journal: Cancer Research (2013)

The article titled “p53 Regulates Cellular Resistance to Complement Lysis through Enhanced Expression of CD59,” which was published in the February 15, 2006, issue of Cancer Research (1), is being retracted at the request of the authors following the release of the conclusions of an internal investigation panel established by Cardiff University to examine allegations of research misconduct in the preparation of the manuscript. The panel found evidence of splicing or pasting affecting Figs. 1B and 4A, without indication that this had been done. The panel feels that although these image manipulations cannot be characterized as “fabrication” because there is no reason to doubt the validity of the underlying science in the article, they represent unacceptable practice when submitting a manuscript for publication. Dr. R.M. Donev accepted full responsibility for these actions. The panel concluded that none of the other coauthors of this manuscript knew, or had reason to suspect, that the data presented in the manuscript had been manipulated by Dr. R.M. Donev.Four of the five authors agreed to this Retraction. Attempts to contact the first author, Rossen M. Donev, were unsuccessful.
Identification of miR-29c and its Target FBXO31 as a Key Regulatory Mechanism in Esophageal Cancer Chemoresistance: Functional Validation and Clinical Significance
Authors: Bin Li, Pan Hong, Can-Can Zheng, Wei Dai, Wen-You Chen, Qing-Sheng Yang, Liang Han, Sai Wah Tsao, Kin Tak Chan, Nikki Pui Yue Lee, Simon Law, Li Yan Xu, En Min Li, Kwok Wah Chan, Yan Ru Qin, Xin Yuan Guan, Maria Li Lung, Qing-Yu He, Wen Wen Xu, Annie LM Cheung
Journal: Theranostics (2019)

Rationale: Dysregulated microRNA (miRNA) expressions in cancer can contribute to chemoresistance.This study aims to identify miRNAs that are associated with fluorouracil (5-FU) chemoresistance in esophageal squamous cell carcinoma (ESCC).The potential of miR-29c as a novel diagnostic, prognostic and treatment-predictive marker in ESCC, and its mechanisms and therapeutic implication in overcoming 5-FU chemoresistance were explored.Methods: The miRNA profiles of an ESCC cell model with acquired chemoresistance to 5-FU were analyzed using a Taqman miRNA microarray to identify novel miRNAs associated with 5-FU chemoresistance.Quantitative real-time PCR was used to determine miR-29c expression in tissue and serum samples of patients.Bioinformatics, gain-and loss-of-function experiments, and luciferase reporter assay were performed to validate F-box only protein 31 (FBXO31) as a direct target of miR-29c, and to identify potential transcription factor binding events that control miR-29c expression.The potential of systemic miR-29c oligonucleotide-based therapy in overcoming 5-FU chemoresistance was evaluated in tumor xenograft model.Results: MiR-29c, under the regulatory control of STAT5A, was frequently downregulated in tumor and serum samples of patients with ESCC, and the expression level was correlated with overall survival.Functional studies showed that miR-29c could override 5-FU chemoresistance in vitro and in vivo by directly interacting with the 3'UTR of FBXO31, leading to repression of FBXO31 expression and downstream activation of p38 MAPK.Systemically administered miR-29c dramatically improved response of 5-FU chemoresistant ESCC xenografts in vivo.Conclusions: MiR-29c modulates chemoresistance by interacting with FBXO31, and is a promising non-invasive biomarker and therapeutic target in ESCC.
EPR19-066: Trends in Primary Squamous Cell Penile Cancer: A SEER Study
Authors: Scott Cooper, Mohammed Zaher, Gregory Diorio
Journal: Journal of the National Comprehensive Cancer Network (2019)

Objective: Although rare worldwide, primary squamous cell penile cancer (PSPC) is associated with significant psychological stress and cancer-specific mortality. We aim to analyze trends in PSPC in the United States from 2000–2015 using U.S. Surveillance, Epidemiology, and End Results registry (SEER). Clinical identification of risk factors for adverse outcomes will allow for patient-specific counseling on prognosis and intervention. Methods: Population-based data from SEER 18 was used to assess PSPC. SEER Stat was used to calculate incidence, mortality, and survival statistics of PSPC, as well as demographic, geographic, socioeconomic, and clinical variables from 2000 to 2015. Trends were assessed over 5-year spans (2000–2005, 2006–2010, and 2011–2015) using annual percent change. Kaplan-Meier logistic regression analysis was used to calculate 5-year, cancer-specific survival. Results: From 2000–2015, 5,144 men in the U.S. were diagnosed with PSPC at a rate of 0.38 per 100,000, which remained unchanged throughout the entire study period. Asians and Pacific Islanders had the lowest incidence (0.02, 95% CI=0.2, 0.2; P &lt;.05) of all racial groups. Hispanics had a higher incidence (0.58, 95% CI=0.54, 0.62; P &lt;.05) than non-Hispanics. Incidence was highest in the South (0.46, 95% CI=0.43, 0.48; P &lt;.05); however, cancer-specific mortality was similar across regions. No difference in mortality was observed between urban and rural dwelling. Those lacking a high school education and living in areas with more than 10% poverty had a greater incidence of PSPC than others ( P &lt;.05). Overall, 5-year cancer-specific survival was 57%, which remained consistent across each studied time interval ( P &lt;.05). Compared to previous years, those diagnosed between 2011 and 2015 lacked surgical intervention, were of advanced age (&gt;74–85 years), stage (T1, T2, T3), and with greater lymph node burden (&gt;4) ( P &lt;.05). Increased mortality was associated with unmarried men, &gt;20% poverty rate, advanced age, advanced T stage, and lack of surgical treatment ( P &lt;.05). Conclusion: Disparity in PSPC continues to exist. Incidence of penile cancer has increased with advanced age and stage. Unmarried, impoverished men with advanced stage and lack of surgical treatment have increased cancer-specific mortality. Efforts should be directed to those most at risk with hopes to identify disease at an earlier stage to provide surgical treatment with curative intent.
Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy
Authors: Marie-Eve Beaulieu, Toni Jauset, Daniel Massó-Vallés, Sandra Martínez-Martín, Peter Rahl, Loïka Maltais, Mariano F. Zacarias-Fluck, Sílvia Casacuberta-Serra, Erika Serrano del Pozo, Christopher Fiore, Laia Foradada, Virginia Castillo Cano, Meritxell Sánchez-Hervás, Matthew Guenther, Eduardo Romero Sanz, Marta Oteo, Cynthia Tremblay, Génesis Martín, Danny Letourneau, Martin Montagne, Miguel Ángel Morcillo Alonso, Jonathan R. Whitfield, Pierre Lavigne, Laura Soucek
Journal: Science Translational Medicine (2019)

We demonstrate the pharmacologic potential of the purified cell-penetrating Omomyc mini-protein to directly inhibit MYC function in vitro and in vivo.
Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance
Authors: Kun Chen, Xiaoting Luan, Qisha Liu, Jianwei Wang, Xinxia Chang, Antoine M. Snijders, Jian-Hua Mao, Julie Secombe, Zhou Dan, Jian-Huan Chen, Zibin Wang, Xiao Dong, Chen Qiu, Xiaoai Chang, Dong Zhang, Susan E. Celniker, Xingyin Liu
Journal: Cell Host & Microbe (2019)
QIM19-118: Oral Anti-Cancer Therapy Initiation: A Standardized Approach for Patient Care and Education
Authors: Megan Corbett, Cynthia Arcieri, Emma Dann, Jeff Durney, Frances Fuller, Frances Leonard, Susan O’Connor, Inez Robinson, Jill Sweeney, Kristie Weeks, Jamie White, Jane Worrell
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The availability and popularity of oral anti-cancer therapy has recently increased. In this shift of delivery, control over downstream steps in the process moves to patients, families, and the extended care team. Unique challenges have been identified including effective patient education, adherence, and monitoring. The purpose of this quality improvement project was to standardize the approach to initiating oral anti-cancer patient care. Methods: A quality improvement team developed and implemented a standard approach for before, during, and after initiation of oral anti-cancer therapy. Key components included ensuring completion of informed consent, electronic orders within an evidence-based treatment plan, and adherence monitoring with a specific emphasis on patient education. Education prior to initiating therapy was standardized through both an education folder and one-on-one teaching sessions with an oncology nurse. A voluntary, anonymous 4-question paper survey (deemed clinical quality improvement by the IRB) solicited feedback from patients to assess both the educational materials and teaching session. Questions included perceived acceptability of the content and whether materials guided conversation, provoked questions, and complimented the teaching. An opportunity for comments was provided. Results: A 3-month collection period yielded overwhelmingly positive results. 100% of patients (n=18) felt the education materials provided were “just right” and provoked discussion with the care team. 94% of patients felt the educational materials and teaching session were complimentary. Conclusions: As oral anti-cancer therapy becomes more common, it is vital to form a collaborative partnership with the patient, family, and the extended care team to ensure overall success. Standardized educational content supports the transfer of expert knowledge to ensure adherence, management, and patient safety, ultimately improving patient outcomes. A standard approach that includes informed consent, orders within a treatment plan, adherence monitoring, and patient education prior to initiating oral anti-cancer therapy is one way to ensure quality, comprehensive patient care.
Monocyte-Derived CD11c+ Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria
Authors: Samarchith P. Kurup, Scott M. Anthony, Lisa S. Hancox, Rahul Vijay, Lecia L. Pewe, Steven J. Moioffer, Ramakrishna Sompallae, Chris J. Janse, Shahid M. Khan, John T. Harty
Journal: Cell Host & Microbe (2019)