tbuckley/cabot-search huggingface dataset:
Survival in Patients With Sentinel Node–Positive Melanoma With Extranodal Extension
Authors: Andrea Maurichi, Francesco Barretta, Roberto Patuzzo, Rosalba Miceli, Gianfranco Gallino, Ilaria Mattavelli, Consuelo Barbieri, Andrea Leva, Martina Angi, Francesco Baldo Lanza, Giuseppe Spadola, Mara Cossa, Francesco Nesa, Umberto Cortinovis, Laura Sala, Lorenza Di Guardo, Carolina Cimminiello, Michele Del Vecchio, Barbara Valeri, Mario Santinami
Journal: Journal of the National Comprehensive Cancer Network (2021)

Prognostic parameters in sentinel node (SN)-positive melanoma are important indicators to identify patients at high risk of recurrence who should be candidates for adjuvant therapy. We aimed to evaluate the presence of melanoma cells beyond the SN capsule-extranodal extension (ENE)-as a prognostic factor in patients with positive SNs.Data from 1,047 patients with melanoma and positive SNs treated from 2001 to 2020 at the Istituto Nazionale dei Tumori in Milano, Italy, were retrospectively investigated. Kaplan-Meier survival and crude cumulative incidence of recurrence curves were estimated. A multivariable logistic model was used to investigate the association between ENE and selected predictive factors. Cox models estimated the effect of the selected predictors on survival endpoints.Median follow-up was 69 months. The 5-year overall survival rate was 62.5% and 71.7% for patients with positive SNs with and without ENE, respectively. The 5-year disease-free survival rate was 54.0% and 64.0% for patients with positive SNs with and without ENE, respectively. The multivariable logistic model showed that age, size of the main metastatic focus in the SN, and numbers of metastatic non-SNs were associated with ENE (all P<.0001). The multivariable Cox regression models showed the estimated prognostic effects of ENE associated with age, ulceration, size of the main metastatic focus in the SN, and number of metastatic non-SNs (all P<.0001) on disease-free survival and overall survival.ENE was a significant prognostic factor in patients with positive-SN melanoma. This parameter may be useful in clinical practice as a selection criterion for adjuvant treatment in patients with stage IIIA disease with a tumor burden <1 mm in the SN. We recommend its inclusion as an independent prognostic determinant in future updates of melanoma guidelines.
Variants on the <scp><i>UBE2L3</i></scp>/<scp><i>YDJC</i></scp> Autoimmune Disease Risk Haplotype Increase <scp><i>UBE2L3</i></scp> Expression by Modulating <scp>CCCTC‐Binding</scp> Factor and YY1 Binding
Authors: Jaanam Gopalakrishnan, Kandice L. Tessneer, Yao Fu, Satish Pasula, Richard C. Pelikan, Jennifer A. Kelly, Graham B. Wiley, Patrick M. Gaffney
Journal: Arthritis & Rheumatology (2021)

Objective Genetic variants spanning UBE2L3 are associated with increased expression of the UBE2L3 ‐encoded E2 ubiquitin‐conjugating enzyme H7 (UbcH7), which facilitates activation of proinflammatory NF‐κB signaling and susceptibility to autoimmune diseases. We undertook this study to delineate how genetic variants carried on the UBE2L3/YDJC autoimmune risk haplotype function to drive hypermorphic UBE2L3 expression. Methods We used bioinformatic analyses, electrophoretic mobility shift assays, and luciferase reporter assays to identify and functionally characterize allele‐specific effects of risk variants positioned in chromatin accessible regions of immune cells. Chromatin conformation capture with quantitative polymerase chain reaction (3C‐qPCR), chromatin immunoprecipitation (ChIP)–qPCR, and small interfering RNA (siRNA) knockdown assays were performed on patient‐derived Epstein‐Barr virus–transformed B cells homozygous for the UBE2L3 / YDJC nonrisk or risk haplotype to determine if the risk haplotype increases UBE2L3 expression by altering the regulatory chromatin architecture in the region. Results Of the 7 prioritized variants, 5 demonstrated allele‐specific increases in nuclear protein binding affinity and regulatory activity. High‐throughput sequencing of chromosome conformation capture coupled with ChIP (HiChIP) and 3C‐qPCR uncovered a long‐range interaction between the UBE2L3 promoter (rs140490, rs140491, rs11089620) and the downstream YDJC promoter (rs3747093) that was strengthened in the presence of the UBE2L3 / YDJC risk haplotype, and correlated with the loss of CCCTC‐binding factor (CTCF) and gain of YY1 binding at the risk alleles. Depleting YY1 by siRNA disrupted the long‐range interaction between the 2 promoters and reduced UBE2L3 expression. Conclusion The UBE2L3 / YDJC autoimmune risk haplotype increases UBE2L3 expression through strengthening a YY1‐mediated interaction between the UBE2L3 and YDJC promoters.
Abstract 14781: Tie2-expressing Monocytes: An Angiogenic Target In Tissue Ischaemia
Authors: Ashish S Patel, Alberto Smith, Prakash Saha, Katherine Mattock, Julia Humphries, Matthew Waltham, Richard Siow, Aleksandar Ivetic, Stuart Egginton, Bijan Modarai
Journal: Circulation (2011)

Introduction Angiogenic cell therapy using unselected populations of mononuclear cells has been of limited benefit in the revascularisation of critically ischaemic tissue. Monocytes expressing the ...
Adverse event burden in older patients with CLL receiving bendamustine plus rituximab or ibrutinib regimens: Alliance A041202
Authors: Amy S. Ruppert, Allison M. Booth, Wei Ding, Nancy L. Bartlett, Danielle M. Brander, Steven Coutre, Jennifer R. Brown, Sreenivasa Nattam, Richard A. Larson, Harry Erba, Mark Litzow, Carolyn Owen, Charles S. Kuzma, Jeremy S. Abramson, Richard F. Little, Scott E. Smith, Richard M. Stone, John C. Byrd, Sumithra J. Mandrekar, Jennifer A. Woyach
Journal: Leukemia (2021)
Management of viral haemorrhagic fevers in Switzerland
Authors: S Hugonnet, Hugo Sax, D Pittet
Journal: Eurosurveillance (2002)

Over the past years, there have been very few imported cases of VHF in Switzerland: one confirmed and four suspected cases of Ebola fever in Basel in 1994, two suspected cases of Ebola and Lassa fevers in Lausanne in 2000, and in the same year, six suspected cases of Lassa fever in Geneva. Given the considerable diversity in the management of patients with suspected or confirmed VHF, national guidelines are needed, as well as the establishment of a national reference centre.
Abstract 8425: Fetal Cardiac Ventricular Volume and Mass Derived from Spatio-Temporal Image Correlation
Authors: Boris Tutschek, Jochen Ritgen, Minjuan Zhang, Xiaokui Li, David J Sahn
Journal: Circulation (2011)

Background: Fetal cardiac assessment is usually performed qualitatively. Functional and longitudinal studies of abnormal fetuses would benefit from reproducible quantitative cardiac measurements. We used spatio-temporal image correlation (STIC) to measure left and right ventricular (LV, RV) volumes and masses in normal and structurally abnormal fetal hearts. Methods: 44 normal fetuses and 7 with structural heart disease (dextrocardia, DORV, d-TGA, HLHS, pulmonary stenosis PS, VSD) at gestational ages between 16 and 38 completed weeks were included. STIC volumes were acquired and analyzed in end-diastole and end-systole according to an established and validated method. Results: Measurements were possible in all fetuses. Ventricular volumes and masses increased with gestation. In fetal DORV, HLHS and PS, RV volumes were increased, in DORV and PS, RV mass was increased. In normal hearts, RV mass was 20% higher than LV mass throughout gestation, but the ejection fraction was slightly higher in the LV. Conclusions: Using STIC the human fetal heart can be studied quantitatively, taking into account the complex geometry especially related to the right ventricle.
Multiple Facial Ulcers Following a Stroke
Authors: Beke Esther Linnemann, Alexander Neumann, Iakov Shimanovich
Journal: JAMA Neurology (2021)

A 66-year-old man presents with multiple progressive ulcers and hypoesthesia on the right side of his face, new-onset hemiplegia and hemianopsia on the left side of his face, and ischemic posterior circulation stroke. What is your diagnosis?
Cost-effectiveness of Dapagliflozin for the Treatment of Heart Failure With Reduced Ejection Fraction
Authors: Nicolas Isaza, Paola Calvachi, Inbar Raber, Chia-Liang Liu, Brandon K. Bellows, Inmaculada Hernandez, Changyu Shen, Michael C. Gavin, A. Reshad Garan, Dhruv S. Kazi
Journal: JAMA Network Open (2021)

Heart failure with reduced ejection fraction produces substantial morbidity, mortality, and health care costs. Dapagliflozin is the first sodium-glucose cotransporter 2 inhibitor approved for the treatment of heart failure with reduced ejection fraction.To examine the cost-effectiveness of adding dapagliflozin to guideline-directed medical therapy for heart failure with reduced ejection fraction in patients with or without diabetes.This economic evaluation developed and used a Markov cohort model that compared dapagliflozin and guideline-directed medical therapy with guideline-directed medical therapy alone in a hypothetical cohort of US adults with similar clinical characteristics as participants of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial. Dapagliflozin was assumed to cost $4192 annually. Nonparametric modeling was used to estimate long-term survival. Deterministic and probabilistic sensitivity analyses examined the impact of parameter uncertainty. Data were analyzed between September 2019 and January 2021.Lifetime incremental cost-effectiveness ratio in 2020 US dollars per quality-adjusted life-year (QALY) gained.The simulated cohort had a starting age of 66 years, and 41.8% had diabetes at baseline. Median (interquartile range) survival in the guideline-directed medical therapy arm was 6.8 (3.5-11.3) years. Dapagliflozin was projected to add 0.63 (95% uncertainty interval [UI], 0.25-1.15) QALYs at an incremental lifetime cost of $42 800 (95% UI, $37 100-$50 300), for an incremental cost-effectiveness ratio of $68 300 per QALY gained (95% UI, $54 600-$117 600 per QALY gained; cost-effective in 94% of probabilistic simulations at a threshold of $100 000 per QALY gained). Findings were similar in individuals with or without diabetes but were sensitive to drug cost.In this study, adding dapagliflozin to guideline-directed medical therapy was projected to improve long-term clinical outcomes in patients with heart failure with reduced ejection fraction and be cost-effective at current US prices. Scalable strategies for improving uptake of dapagliflozin may improve long-term outcomes in patients with heart failure with reduced ejection fraction.
Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study
Authors: Susan D Hillis, H Juliette T Unwin, Yu Chen, Lucie Cluver, Lorraine Sherr, Philip S Goldman, Oliver Ratmann, Christl A Donnelly, Samir Bhatt, Andrés Villaveces, Alexander Butchart, Gretchen Bachman, Laura Rawlings, Phil Green, Charles A Nelson, Seth Flaxman
Journal: The Lancet (2021)

BackgroundThe COVID-19 pandemic priorities have focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalisation. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation.MethodsWe used mortality and fertility data to model minimum estimates and rates of COVID-19-associated deaths of primary or secondary caregivers for children younger than 18 years in 21 countries. We considered parents and custodial grandparents as primary caregivers, and co-residing grandparents or older kin (aged 60–84 years) as secondary caregivers. To avoid overcounting, we adjusted for possible clustering of deaths using an estimated secondary attack rate and age-specific infection–fatality ratios for SARS-CoV-2. We used these estimates to model global extrapolations for the number of children who have experienced COVID-19-associated deaths of primary and secondary caregivers.FindingsGlobally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000–1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000–1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0). Numbers of children orphaned exceeded numbers of deaths among those aged 15–50 years. Between two and five times more children had deceased fathers than deceased mothers.InterpretationOrphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children.FundingUK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, Medical Research Council), UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.
Colon Cancer Clinical Practice Guidelines in Oncology
Journal: Journal of the National Comprehensive Cancer Network (2003)

Colorectal cancer is the third most frequently diagnosed cancer in men and women in the United States, and in 2002, an estimated 107,300 new cases of colon cancer will have occurred. Despite these statistics, mortality from colon cancer has decreased over the past 30 years, possibly because of earlier diagnosis through screening and better treatment modalities. The NCCN clinical practice guidelines for managing colon cancer discuss these advances and provide a comprehensive management algorithm. For the most recent version of the guidelines, please visit NCCN.org
Sexual Antagonism, Temporally Fluctuating Selection, and Variable Dominance Affect a Regulatory Polymorphism in <i>Drosophila melanogaster</i>
Authors: Amanda Glaser-Schmitt, Meike J Wittmann, Timothy J S Ramnarine, John Parsch
Journal: Molecular Biology and Evolution (2021)

Abstract Understanding how genetic variation is maintained within species is a major goal of evolutionary genetics that can shed light on the preservation of biodiversity. Here, we examined the maintenance of a regulatory single-nucleotide polymorphism (SNP) of the X-linked Drosophila melanogaster gene fezzik. The derived variant at this site is at intermediate frequency in many worldwide populations but absent in populations from the ancestral species range in sub-Saharan Africa. We collected and genotyped wild-caught individuals from a single European population biannually over a period of 5 years, which revealed an overall difference in allele frequency between the sexes and a consistent change in allele frequency across seasons in females but not in males. Modeling based on the observed allele and genotype frequencies suggested that both sexually antagonistic and temporally fluctuating selection may help maintain variation at this site. The derived variant is predicted to be female-beneficial and mostly recessive; however, there was uncertainty surrounding our dominance estimates and long-term modeling projections suggest that it is more likely to be dominant. By examining gene expression phenotypes, we found that phenotypic dominance was variable and dependent upon developmental stage and genetic background, suggesting that dominance may be variable at this locus. We further determined that fezzik expression and genotype are associated with starvation resistance in a sex-dependent manner, suggesting a potential phenotypic target of selection. By characterizing the mechanisms of selection acting on this SNP, our results improve our understanding of how selection maintains genetic and phenotypic variation in natural populations.
Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion
Authors: Trevor Simard, Richard G. Jung, Kyle Lehenbauer, Kerstin Piayda, Radoslaw Pracoń, Gregory G. Jackson, Eduardo Flores-Umanzor, Laurent Faroux, Kasper Korsholm, Julian K.R. Chun, Shaojie Chen, Moniek Maarse, Kristi Montrella, Zakeih Chaker, Jocelyn N. Spoon, Luigi E. Pastormerlo, Felix Meincke, Abhishek C. Sawant, Carmen M. Moldovan, Mohammed Qintar, Mehmet K. Aktas, Luca Branca, Andrea Radinovic, Pradhum Ram, Rayan S. El-Zein, Thomas Flautt, Wern Yew Ding, Bassel Sayegh, Tomás Benito-González, Oh-Hyun Lee, Solomon O. Badejoko, Christina Paitazoglou, Nabeela Karim, Ahmed M. Zaghloul, Himanshu Agrawal, Rachel M. Kaplan, Oluseun Alli, Aamir Ahmed, Hussam S. Suradi, Bradley P. Knight, Venkata M. Alla, Sidakpal S. Panaich, Tom Wong, Martin W. Bergmann, Rashaad Chothia, Jung-Sun Kim, Armando Pérez de Prado, Raveen Bazaz, Dhiraj Gupta, Miguel Valderrabano, Carlos E. Sanchez, Mikhael F. El Chami, Patrizio Mazzone, Marianna Adamo, Fred Ling, Dee Dee Wang, William O’Neill, Wojtek Wojakowski, Ashish Pershad, Sergio Berti, Daniel Spoon, Akram Kawsara, George Jabbour, Lucas V.A. Boersma, Boris Schmidt, Jens Erik Nielsen-Kudsk, Josep Rodés-Cabau, Xavier Freixa, Christopher R. Ellis, Laurent Fauchier, Marcin Demkow, Horst Sievert, Michael L. Main, Benjamin Hibbert, David R. Holmes, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2021)
Metachronous な再発を繰り返した頭蓋内yolk sac tumor の一例
Authors: 祐士 木部, 寿 波多野, 意秀 稲尾, 圭志 伊藤, 健人 羽生, 健太郎 和田, 繁 藤谷, 健一 服部
Journal: Neuro-Oncology (2020)
Guidance for Implementing COVID-19 Prevention Strategies in the Context of Varying Community Transmission Levels and Vaccination Coverage
Authors: Athalia Christie, John T. Brooks, Lauri A. Hicks, Erin K. Sauber-Schatz, Jonathan S. Yoder, Margaret A. Honein
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 vaccination remains the most effective means to achieve control of the pandemic.In the United States, COVID-19 cases and deaths have markedly declined since their peak in early January 2021, due in part to increased vaccination coverage (1).However, during June 19-July 23, 2021, COVID-19 cases increased approximately 300% nationally, followed by increases in hospitalizations and deaths, driven by the highly transmissible B.1.617.2 (Delta) variant* of SARS-CoV-2, the virus that causes COVID-19.Available data indicate that the vaccines authorized in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) offer high levels of protection against severe illness and death from infection with the Delta variant and other currently circulating variants of the virus (2).Despite widespread availability, vaccine uptake has slowed nationally with wide variation in coverage by state (range = 33.9%-67.2%)and by county (range = 8.8%-89.0%).† Unvaccinated persons, as well as persons with certain immunocompromising conditions (3), remain at substantial risk for infection, severe illness, and death, especially in areas where the level of SARS-CoV-2 community transmission is high.The Delta variant is more than two times as transmissible as the original strains circulating at the start of the pandemic and is causing large, rapid increases in infections, which could compromise the capacity of some local and regional health care systems to provide medical care for the communities they serve.Until vaccination coverage is high and community transmission is low, public health practitioners, as well as schools, businesses, and institutions (organizations) need to regularly assess the need for prevention strategies to avoid stressing health care capacity and imperiling adequate care for both COVID-19 and other non-COVID-19 conditions.CDC recommends five critical factors be considered to inform local decisionmaking: 1) level of SARS-CoV-2 community transmission; 2) health system capacity; 3) COVID-19 vaccination coverage; 4) capacity for early detection of increases in COVID-19 cases; * Point-in-time information is available from CDC COVID Data Tracker.https:// covid.cdc.gov/covid-
<i>QuickStats:</i> Age-Adjusted Death Rates* for Motor Vehicle Traffic Injury<sup />— United States, 2016
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

V82.1,V83-V86[.0-.3],V87[.0-.8],V89.2).In 2016, the death rate in the United States for motor vehicle traffic injury was 11.7 per 100,000 standard population.The three states with the highest age-adjusted death rates were Mississippi (25.4), Alabama (23.3), and South Carolina (20.9).New York (5.3), Rhode Island (5.0), and the District of Columbia (4.5) had the lowest rates.
P33-1 Clinical feasibility of approved multigene panels in a Japanese local cancer accredited hospital
Authors: Nahomi Tokudome, Hiroki Ueda, Yuta Hamano, Yasuhiro Koh, Yuichi Ozawa, Kenji Matsuda, Sawako Minami, Miwako Miyasaka, Reiko Ashida, Shinichi Murata, Nobuyuki Yamamoto
Journal: Annals of Oncology (2021)
Daniel H. Mintz (1930–2020): An Extraordinary Physician-Scientist and a Pioneer in Islet Transplantation
Authors: Rodolfo Alejandro, Alessia Fornoni, Luigi Meneghini, Alberto Pugliese, Ronald B. Goldberg
Journal: Diabetes Care (2021)

Daniel H. Mintz Fig. 1 was born in Far Rockaway, New York, in 1930 to European Jewish parents, Jacob and Fanny, and grew up on Long Island, New York, where his parents immigrated in the early 1900s. In his youth he excelled both in sports (basketball) and academically; he was accepted as a premed student at St. Bonaventure College, where he completed his Bachelor’s degree cum laude. He entered New York Medical College, which had no quotas for Jewish students (unlike many other schools at that time), and completed his medical training in 1956. (Fig. 2) While serving his internship at Henry Ford Hospital in Detroit, Michigan, he met his future wife, Dawn, a hospital nurse. In 1961, Dan entered residency at Georgetown University School of Medicine and joined the faculty, initiating his research career under the mentorship of Dr. Larry Kyle, Chairman of Medicine, studying parathyroid and bone disorders (1).



Daniel Mintz in 2006.





Daniel Mintz as a young student, and with his parents and sister at his medical graduation ceremony, New York Medical College, 1956.



Dan’s first love was clinical medicine, so it is no surprise that he was appointed Chief of Medicine at the then District of Columbia General Hospital in 1964. He once recounted the story that kept him in academic medicine after planning to start a private practice in Leesburg, Northern Virginia. Dr. Kyle called him into his office and told him in no uncertain terms that he was making a mistake and should remain in academia. As Dan recalled years later, “In those days you did what your boss told you to do!” This career-changing decision was a testament to Dan’s primary reason for entering medicine—to be a healer of the sick. His capacity for responding to people in need strongly influenced his …
Low-Toxicity/High-Efficacy HLA Haploidentical Transplantation for Elderly/Unfit Patients with Acute Leukemia
Authors: Andrea Velardi, Alessandra Carotti, Franca Falzetti, Adelmo Terenzi, Loredana Ruggeri, Antonio Pierini, Sara Piccinelli, Sara Tricarico, Amico Lucia, Genni Casarola, Valentina Lancillotta, Simonetta Saldi, Mauro Di Ianni, Cynthia Aristei, Massimo Fabrizio Martelli
Journal: Blood (2017)
High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid
Authors: Ja-Seong Bae, Seung-Hyun Jung, Mitsuyoshi Hirokawa, Andrey Bychkov, Akira Miyauchi, Sohee Lee, Yeun-Jun Chung, Chan Kwon Jung
Journal: Endocrine Pathology (2021)