tbuckley/cabot-search huggingface dataset:
Cancer Cells Retrace a Stepwise Differentiation Program during Malignant Progression
Authors: Sadegh Saghafinia, Krisztian Homicsko, Annunziata Di Domenico, Stephan Wullschleger, Aurel Perren, Ilaria Marinoni, Giovanni Ciriello, Iacovos P. Michael, Douglas Hanahan
Journal: Cancer Discovery (2021)

Pancreatic neuroendocrine tumors (PanNET) comprise two molecular subtypes, relatively benign islet tumors (IT) and invasive, metastasis-like primary (MLP) tumors. Until now, the origin of aggressive MLP tumors has been obscure. Herein, using multi-omics approaches, we revealed that MLP tumors arise from IT via dedifferentiation following a reverse trajectory along the developmental pathway of islet β cells, which results in the acquisition of a progenitor-like molecular phenotype. Functionally, the miR-181cd cluster induces the IT-to-MLP transition by suppressing expression of the Meis2 transcription factor, leading to upregulation of a developmental transcription factor, Hmgb3. Notably, the IT-to-MLP transition constitutes a distinct step of tumorigenesis and is separable from the classic proliferation-associated hallmark, temporally preceding accelerated proliferation of cancer cells. Furthermore, patients with PanNET with elevated HMGB3 expression and an MLP transcriptional signature are associated with higher-grade tumors and worse survival. Overall, our results unveil a new mechanism that modulates cancer cell plasticity to enable malignant progression. SIGNIFICANCE: Dedifferentiation has long been observed as a histopathologic characteristic of many cancers, albeit inseparable from concurrent increases in cell proliferation. Herein, we demonstrate that dedifferentiation is a mechanistically and temporally separable step in the multistage tumorigenesis of pancreatic islet cells, retracing the developmental lineage of islet β cells.This article is highlighted in the In This Issue feature, p. 2355.
Assessment of Length and Readability of Informed Consent Documents for COVID-19 Vaccine Trials
Authors: Ezekiel J. Emanuel, Connor W. Boyle
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Informed consent is a fundamental element of research ethics. The COVID-19 vaccine trials are high profile trials that have enrolled more than 100 000 participants. Consent documents must be succinct and understandable to ensure informed voluntary participation. <h3>Objective</h3> To assess how well informed consent documents of the COVID-19 vaccine trials achieve the ideal of being succinct and understandable, and to create a shorter, more readable document. <h3>Design, Setting, and Participants</h3> This quality improvement study collected and analyzed the informed consent documents used in 4 COVID-19 vaccine phase III randomized clinical trials to quantitatively assess readability and length and, based on this analysis, created a measurably more accessible informed consent document. Analysis was conducted from October 2020 to January 2021. <h3>Main Outcomes and Measures</h3> The main outcomes were number of words (measured as word count), time-to-read (measured at reading speeds of 175-300 words per minute), language complexity (measured using Flesch-Kincaid Grade Level assessment), and readability (measured using Flesch Reading Ease Score). Secondary outcomes included clarity of how the placebo group could access the vaccine if it is proven safe and effective. The study also examined the length and readability of an improved consent document. <h3>Results</h3> The 4 informed consent documents were a mean (range) of 8333 (7821 to 9340) words long, with a mean (range) 35 (32.6 to 38.9) minutes to read at 240 words per minute. All documents exceeded grade 9 language complexity and scored lower than 60 in the formal reading ease metric, which constitutes difficult. Only 1 document specified that participants in the placebo group might receive vaccine. It was possible to write a document in fewer than 3000 words with a grade 7 to 8 reading level and a formal readability score that was not difficult. <h3>Conclusions and Relevance</h3> These findings suggest that existing COVID-19 vaccine informed consent documents were too long, difficult to read, and exceeded grade 9 in language complexity. It was possible to create a shorter, more readable informed consent document for these trials.
DON’T FEAR THE RIGHT: RIGHT-SIDED HEART FAILURE DUE TO CORONARY DISSECTION, SALVAGED USING RIGHT SIDED PERCUTANEOUS MICROAXIAL HEMODYNAMIC SUPPORT, GUIDELINER AND WHISPER WIRE
Authors: Frans Beerkens, Victor Razuk, Nikola Kocovic, Ali Omar, Tafadzwa Mtisi, Michael Allen, Gregory Serrao, Sahil Khera, David Power
Journal: Journal of the American College of Cardiology (2021)
Refocusing the Immune Response to Selected Epitopes on a Zika Virus Protein Antigen by Nanopatterning
Authors: Ana Castro, Juan Manuel Carreño, James Duehr, Florian Krammer, Ravi S. Kane
Journal: Advanced Healthcare Materials (2021)

Abstract Infections with Zika virus (ZIKV) are linked to the development of severe central nervous system disorders, but the need for a ZIKV vaccine remains unmet. Although the design of vaccines that elicit antibodies targeting domain III (DIII) of the ZIKV envelope (E) protein as an antigen is an attractive strategy, poorly neutralizing or cross‐reactive antibodies that target the E protein may lead to antibody‐dependent enhancement of disease. It is therefore decided to use the previously reported nanopatterning technique, which combines the site‐specific incorporation of non‐canonical amino acids with site‐specific functionalization of the protein with polyethylene glycol (PEG), to shield selected epitopes on DIII. Two different nanopatterned DIII variants are designed and characterized and demonstrate that epitope shielding with PEG completely inhibits the binding of epitope‐specific antibodies in vitro. Furthermore, immunization with multivalent nanopatterned DIII antigens results in the refocusing of the antibody response toward the exposed epitopes on the protein surface and away from potentially enhancing epitopes. This ability to redirect the antibody response toward targeted regions of the DIII protein should be useful for the design of effective and safe ZIKV vaccines.
The Risks of Polycystic Ovary Syndrome and Diabetes Vary by Ethnic Subgroup Among Young Asian Women
Authors: Lynn Guo, Nancy P. Gordon, Malini Chandra, Olumayowa Dayo, Joan C. Lo
Journal: Diabetes Care (2021)

Previous studies demonstrated that aggregation of Asians into one group masks the variation in type 2 diabetes prevalence across U.S. Asian subgroups. However, fewer studies have assessed Asian ethnic differences in the risk of other conditions associated with insulin resistance and glucose dysregulation. Furthermore, despite the known association of polycystic ovary syndrome (PCOS) and insulin resistance (1), the risks of PCOS and diabetes, accounting for differences in adiposity, have not been investigated in the same U.S. Asian subgroup. To better understand the variation in diabetes and PCOS risk in Asians, we examined these clinical conditions among Chinese, Filipina, and South Asian women identified from a large U.S. population cohort.

Using data from Kaiser Permanente Northern California, we conducted a cross-sectional, retrospective study of 19,258 Chinese, 23,213 Filipina, and 19,108 South Asian women aged 21–44 years who had ≥1 clinical encounter in 2016 with measured (nongestational) weight and height data for calculation of BMI. Self-identified race/ethnicity was derived from electronic health record and survey data, including primary language in a subset, and assignment by ethnic surname was used for Asian women without specified ethnicity (25.2% Chinese, 16.8% Filipina, and 33.9% South Asian). Obesity was classified based on the lower intervention threshold (BMI ≥27.5 kg/m2) recommended for Asians by the American Diabetes Association (2). Smoking status was identified using electronic health …
MALNUTRITION-INFLAMMATION-ATHEROSCLEROSIS (MIA) SYNDROME IS A MAJOR FACTOR TO AFFECT PROGNOSIS OF ELDERLY PATIENTS WITH CHRONIC LIMB-THREATENING ISCHEMIA AFTER ENDOVASCULAR THERAPY
Authors: Takeshi Sonoda, Daisuke Kanda, Ryo Arikawa, Kazuhiro Anzaki, Akihiro Tokushige, Yoshiyuki Ikeda, Mitsuru Ohishi
Journal: Journal of the American College of Cardiology (2021)
MACHINE-LEARNING CHARACTERIZATION OF SUBTLE HEMODYNAMIC INSTABILITY DIFFERENTIATES COVID-19 VERSUS SEASONAL INFLUENZA IN HOSPITALIZED PATIENTS
Authors: Naveena Yanamala, Nanda H. Krishna, Quincy Hathaway, Aditya Radhakrishnan, Srinidhi Sunkara, Heenaben Patel, Peter Farjo, Brijesh Patel, Partho Sengupta
Journal: Journal of the American College of Cardiology (2021)
Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021
Authors: Agam K. Rao, Jeremy Sobel, Kevin Chatham-Stephens, Carolina Luquez
Journal: MMWR Recommendations and Reports (2021)

Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.
ROLE OF RENIN-ANGIOTENSIN MODULATION AND BETA-BLOCKADE IN AORTIC DILATATION IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION
Authors: Maleeha Zahid, Muhammad Saad, Vibha Hayagreev, Neelanjana Pandey, Syed Arsalan Zaidi, Nolberto Hernandez, Heena Sheth, Alaa Omar, Jeirym Miranda, Daniel Alvaro-Garcia, Kang Anthony, Timothy J. Vittorio, Jonathan Bella
Journal: Journal of the American College of Cardiology (2021)
Rigosertib Oral in Transfusion Dependent Lower Risk Myelodysplastic Syndromes (LR-MDS): Optimization of Dose and Rate of Transfusion Independence (TI) or Transfusion Reduction (TR) in a Single-Arm Phase 2 Study
Authors: Azra Raza, Aref Al-Kali, Raoul Tibes, Gary Spitzer, Manila Gaddh, Benjamin Tycko, Sangmin Lee, Naomi Galili, Abdullah Mahmood Ali, John G. Mears, Siddhartha Mukherjee, Ryan Shelton, Steven M. Fruchtman, Michael E. Petrone, Patrick S. Zbyszewski, Mark Lawrence Heaney
Journal: Blood (2017)
OFx: A method of 4D image construction from free-breathing non-gated MRI slice acquisitions of the thorax via optical flux
Authors: You Hao, Jayaram K. Udupa, Yubing Tong, Caiyun Wu, Hua Li, Joseph M. McDonough, Carina Lott, Catherine Qiu, Nirupa Galagedera, Jason B. Anari, Drew A. Torigian, Patrick J. Cahill
Journal: Medical Image Analysis (2021)
Embryo CHH hypermethylation is mediated by RdDM and is autonomously directed in Brassica rapa
Authors: Tania Chakraborty, Timmy Kendall, Jeffrey W. Grover, Rebecca A. Mosher
Journal: Genome biology (2021)

RNA-directed DNA methylation (RdDM) initiates cytosine methylation in all contexts and maintains asymmetric CHH methylation. Mature plant embryos show one of the highest levels of CHH methylation, and it has been suggested that RdDM is responsible for this hypermethylation. Because loss of RdDM in Brassica rapa causes seed abortion, embryo methylation might play a role in seed development. RdDM is required in the maternal sporophyte, suggesting that small RNAs from the maternal sporophyte might translocate to the developing embryo, triggering DNA methylation that prevents seed abortion. This raises the question of whether embryo hypermethylation is autonomously regulated by the embryo itself or influenced by the maternal sporophyte.
LONG-TERM OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH PRIOR CORONARY ARTERY BYPASS GRAFTING
Authors: Stephen Broughton, Ahmet Sezer, Suresh Mulukutla, Arman Kilic, Catalin Toma, Dustin Kliner, Danny Chu, Ibrahim Sultan
Journal: Journal of the American College of Cardiology (2021)
scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing
Authors: Gavin W. Wilson, Mathieu Derouet, Gail E. Darling, Jonathan C. Yeung
Journal: Genome biology (2021)

Abstract Identifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furthermore, molecular duplicates generated in these experiments have not been utilized to optimally detect variant co-expression. Herein, we introduce scSNV designed from the ground up to “collapse” molecular duplicates and accurately identify variants and their co-expression. We demonstrate that scSNV is fast, with a reduced false-positive variant call rate, and enables the co-detection of genetic variants and A&gt;G RNA edits across twenty-two samples.
Abstract 18780: The Impact of Anemia Severity on Angiographic and Clinical Outcomes following Percutaneous Coronary Intervention with Drug-eluting Stents in Asian Population
Authors: Ji Young Park, Seung Woon Rha, Jae Woong Choi, Sung Kee Ryu, Byoung Geol Choi, Se Yeon Choi, Sung Il Im, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2012)

Background: The significance of anemia in patients (pts) undergoing percutaneous coronary intervention (PCI) remains controversial. The aim of this study was to evaluate the impact of the severity of anemia on the angiographic and clinical outcomes following PCI with drug eluting stent (DES). Methods: A total of 881 consecutive pts underwent PCI with DESs were enrolled. Anemia was defined using World Health Organization criteria with hematocrit (Hct): mild anemia (female: 29%≤Hct&lt;36%, male:29%≤Hct&lt;39%, A1, n=485), moderate to severe anemia (Hct&lt;29%, A2, n=50), and no anemia (female: Hct≥36%, male: Hct≥39%, A0, n=507). Six-month angiographic and 1 year clinical outcomes were compared among the three groups. Results: At baseline, the rate of female gender, old age, the incidence of ST elevation myocardial infarction (STEMI), hypertension, diabetes mellitus, chronic renal disease, and congestive heart failure were highest in the Group A2. The incidence of left main and multivessel PCI was highest in the Group A2. At 6 months, the angiographic outcomes were worst in the Group A2. At 12 months, the cumulative incidence of total deaths, any myocardial infarction, and all major adverse cardiac events (MACEs) up to 2 years were highest in the Group A2 (Table). Multivariate analysis showed that anemia was an independent predictor of mortality at 2 years (Adjusted OR 3.78, CI 2.19-6.52, p&lt;0.001). Conclusions: In conclusion, the severity of anemia on admission in pts undergoing PCI with DESs was associated with higher mortality and MACEs up to 2 years, suggesting special care should be exercised when a pt has moderate to severe anemia on admission.
The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective
Authors: Nancy S. Bolous, Yichen Chen, Huiqi Wang, Andrew M. Davidoff, Meenakshi Devidas, Timothy W. Jacobs, Michael M. Meagher, Amit C. Nathwani, Ellis J. Neufeld, Bryan A. Piras, Carlos Rodriguez-Galindo, Ulrike M. Reiss, Nickhill Bhakta
Journal: Blood (2021)

Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. Although multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX (FIX)-Padua gene therapy for patients with severe hemophilia B in the United States vs on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. A microsimulation Markov model was constructed, and transition probabilities between health states and utilities were informed by using published data. Costs were aggregated by using a microcosting approach. A time horizon from 18 years old until death, from the perspective of a third-party payer in the United States, was conducted. Gene therapy was more cost-effective than both alternatives considering a $150 000/quality-adjusted life-year threshold. The price for gene therapy was assumed to be $2 000 000 in the base case scenario; however, one of the 1-way sensitivity analyses was conducted by using observed manufacturing, administration, and 5-year follow-up costs of $87 198 for AAV-mediated gene therapy vector as derived from the manufacturing facility and clinical practice at St Jude Children's Research Hospital. One-way sensitivity analyses revealed 10 of 102 scenarios in which gene therapy was not cost-effective compared with alternative treatments. Notably, gene therapy remained cost-effective in a hypothetical scenario in which we estimated that the discounted factor concentrate price was 20% of the wholesale acquisition cost in the United States. Probabilistic sensitivity analysis estimated gene therapy to be cost-effective at 92% of simulations considering a $150 000/quality-adjusted life-year threshold. In conclusion, based on detailed simulation inputs and assumptions, gene therapy was more cost-effective than on-demand treatment and prophylaxis for patients with severe hemophilia B.
ONE YEAR CLINICAL OUTCOMES IN PATIENTS WITH CORONARY BIFURCATION LESIONS: RESULTS FROM THE RESOLUTE ONYX BIFURCATION STUDY
Authors: Matthew Price, Loukas Boutis, Ajay Kirtane, Stanley Chetcuti, Petra Poliacikova, Joseph Dens, Michael Attubato, Yale Wang, Patrick Hu, Douglas Spriggs, Joshua Krasnow, Yiannis Chatzizisis, Adel Aminian, Ronald Caputo, Alpesh Shah, Michelle Dauler, Sherif Ibrahim, Te-Hsin Lung, Oscar Sanchez, Roxana Mehran
Journal: Journal of the American College of Cardiology (2021)
PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
Authors: Dongyuan Song, Jingyi Jessica Li
Journal: Genome biology (2021)

To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and power.
IS APPROPRIATE USE OF ORAL ANTICOAGULANTS IMPROVING AMONG ATRIAL FIBRILLATION PATIENTS? RESULTS FROM THE BENCHMARKING AN ORAL ANTICOAGULANT TREATMENT RATE IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION (BOAT-AF) STUDY AND COMPARISON TO 387,975 PARTICIPANTS IN THE PINNACLE REGISTRY®
Authors: Joseph Kim, Jane Lee, Julie Sutherland, Clifford Ehrlich, Ravinder Bachireddy, C. Michael Valentine, Nasser Smiley, Steven Hearne, April Trebnick, Sara Jaffer, Sudarshana Datta, Emily Tucker, Fran Thorpe, Yang Song, Gheorghe Doros, Matthew Cavender, Matthew Reynolds, Christopher Cannon
Journal: Journal of the American College of Cardiology (2021)
Immunology Lessons from the SARS-CoV-2 Pandemic
Authors: Wayne M. Yokoyama, Kristin A. Hogquist, John J. O'Shea
Journal: Annual Review of Immunology (2021)

Immunology Lessons from the SARS-CoV-2 Pandemic, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/immunol/39/1/annurev-iy-39-030121-100001-1.gif
Paradox of Resident Case Numbers
Authors: Chad M. Cryer, Kenric M. Murayama
Journal: JAMA Surgery (2021)

Amanda C. Purdy, MD; Christian de Virgilio, MD; Amy H. Kaji, MD, PhD; Edgar Shields Frey, MD; Steven Lee-Kong, MD; Kenji Inaba, MD; Jeffrey M. Gauvin, MD; Angela L. Neville, MD; Timothy R. Donahue, MD; Brian R. Smith, MD; Edgardo S. Salcedo, MD; Kristine E. Calhoun, MD; V. Prasad Poola, MD; Jukes P. Namm, MD; David A. Spain, MD; Karen J. Dickinson, MD; Tiffany Tanner, MD; Mary Wolfe, MD; Farin Amersi, MD
DETERMINANTS OF HOSPITAL LENGTH OF STAY IN PATIENTS WITH HEART FAILURE WITH STABLE MID-RANGE EJECTION FRACTION
Authors: Mohamad Khaled Soufi, Rishabh R. Jain, Joseph R. McFarland, Simon Pinsky, Alexander Dang, Milin N. Rana, Wissam Khalife
Journal: Journal of the American College of Cardiology (2021)
WHEN ETIOLOGIES CONVERGE- NON-COMPACTION AND ISCHEMIC CARDIOMYOPATHY IN A PATIENT WITH HEART FAILURE
Authors: Erica G. Otero-Cardenas, Jorge Juan Ballester Maldonado, Hector Nunez Medina, Jonathan Cordero-Jimé nez, Ariel Gonzalez, Hilton Franqui-Rivera
Journal: Journal of the American College of Cardiology (2021)
In the ED, LUS and CT did not differ for sensitivity or specificity for diagnosing COVID-19 pneumonia
Authors: Jonathan Kirschner, Benton Hunter
Journal: Annals of Internal Medicine (2021)

Lieveld AW, Kok B, Schuit FH, et al. Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT)-a multicentre, prospective, observational study. ERJ Open Res. 2020;6:00539-2020. 33442553.