tbuckley/cabot-search huggingface dataset:
SAT0285 VISUALISATION OF THE ACTIVE CALCIFICATION PROCESS WITH 18-F SODIUM FLUORIDE PET/CT IN LIMITED CUTANEOUS SYSTEMIC SCLEROSIS WITH CALCINOSIS CUTIS IS FEASIBLE: A PILOT STUDY
Authors: I. M. Atzeni, E. M. Hogervorst, G. M. Swart, K. De Leeuw, M. Bijl, R. Bos, J. Westra, G. Diercks, H. Van Goor, M. C. Bolling, R. Slart, D. J. Mulder
Journal: Annals of the Rheumatic Diseases (2020)

Background: Calcinosis cutis is a major daily challenge to patients with longstanding systemic sclerosis (SSc), negatively affecting their quality of life. Unfortunately, treatment options are very limited due to lack of understanding of the pathogenetic process. Currently, calcinosis cutis is only detected at its irreversible end-stage. Early detection of calcinosis cutis could putatively allow early disease-modifying interventions and monitor treatment effects. Objectives: The aim of the current study is to assess the feasibility of visualising “active” micro-calcifications with 18-F Sodium Fluoride (NaF) PET scanning, compared to low-dose CT in patients with clinically overt calcinosis cutis. Methods: This was a cross-sectional, observational, pilot study. All patients met 2013 ACR/EULAR criteria for SSc. Patients underwent a whole body NaF PET/low-dose CT scan, scanned 90 minutes post-injection. (Sub)cutaneous calcifications were described and assessed on NaF PET, which was compared to CT images by two independent investigators. Results: A total of 10 female patients with limited cutaneous SSc [median age 56 years (IQR 52-66), median disease duration 17 years (8-19), PAH 10%, ILD 20%] were included, and compared to 10 controls [70 years (65-73)]. NaF uptake showed normal distribution throughout the skeletal bones, arterial tree, and visceral organs, which was comparable between patients and controls. Additionally, NaF uptake was visible in the skin of all SSc patients, but in none of the controls. Cutaneous NaF uptake largely correlated with clinical calcifications. Most common sites of cutaneous NaF uptake were fingers (6 patients) and knees (7 patients). Only 5% of the NaF positive lesions were not accompanied by visible calcifications on CT. Furthermore, of all calcified lesions seen on CT, 51% showed uptake on NaF PET. Small lesions (&lt;1 cm), were generally only visible on CT, due to lower resolution of NaF PET. Conclusion: Imaging of “active” calcinosis cutis in limited cutaneous systemic sclerosis is feasible using NaF PET scanning. Most clinically overt calcifications and half of those seen on CT were positive for NaF uptake. Whether these “active” calcifications behave differently in terms of faster progression, clinical complaints, and infection risk, and whether these are potentially suitable for disease modifying interventions is subject to future study. Disclosure of Interests: None declared
How Can Journals Respond to Threats of Libel Litigation?
Authors: Nav Persaud, Thom Ringer, Trudo Lemmens
Journal: PLoS Medicine (2014)

Trudo Lemmens and colleagues discuss how the mere suggestion of litigation can bias the medical literature by affecting editorial decisions. They argue that journals and authors should publicly post threats of litigation, or cease and desist letters, for which there are some international legal precedents. Please see later in the article for the Editors' Summary
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development
Authors: Guillermo E. Parada, Roberto Munita, Ilias Georgakopoulos-Soares, Hugo J. R. Fernandes, Veronika R. Kedlian, Emmanouil Metzakopian, Maria Estela Andres, Eric A. Miska, Martin Hemberg
Journal: Genome biology (2021)

Abstract Background Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent results demonstrating the impact of microexons on behaviour and cognition. However, microexons are often overlooked due to the difficulty of detecting them using standard RNA-seq aligners. Results Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We process 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mice. We detect 2984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons based on their inclusion patterns segregates brain tissues by developmental time, and further analysis suggests a key function for microexons in axon growth and synapse formation. Finally, we analyse single-cell RNA-seq data from the mouse visual cortex, and for the first time, we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell type-specific. Conclusions MicroExonator facilitates the investigation of microexons in transcriptome studies, particularly when analysing large volumes of data. As a proof of principle, we use MicroExonator to analyse a large collection of both mouse bulk and single-cell RNA-seq datasets. The analyses enabled the discovery of previously uncharacterized microexons, and our study provides a comprehensive microexon inclusion catalogue during mouse development.
Unraveling the Complex Hybrid Ancestry and Domestication History of Cultivated Strawberry
Authors: Michael A Hardigan, Anne Lorant, Dominique D A Pincot, Mitchell J Feldmann, Randi A Famula, Charlotte B Acharya, Seonghee Lee, Sujeet Verma, Vance M Whitaker, Nahla Bassil, Jason Zurn, Glenn S Cole, Kevin Bird, Patrick P Edger, Steven J Knapp
Journal: Molecular Biology and Evolution (2021)

Abstract Cultivated strawberry (Fragaria × ananassa) is one of our youngest domesticates, originating in early eighteenth-century Europe from spontaneous hybrids between wild allo-octoploid species (Fragaria chiloensis and Fragaria virginiana). The improvement of horticultural traits by 300 years of breeding has enabled the global expansion of strawberry production. Here, we describe the genomic history of strawberry domestication from the earliest hybrids to modern cultivars. We observed a significant increase in heterozygosity among interspecific hybrids and a decrease in heterozygosity among domesticated descendants of those hybrids. Selective sweeps were found across the genome in early and modern phases of domestication—59–76% of the selectively swept genes originated in the three less dominant ancestral subgenomes. Contrary to the tenet that genetic diversity is limited in cultivated strawberry, we found that the octoploid species harbor massive allelic diversity and that F. × ananassa harbors as much allelic diversity as either wild founder. We identified 41.8 M subgenome-specific DNA variants among resequenced wild and domesticated individuals. Strikingly, 98% of common alleles and 73% of total alleles were shared between wild and domesticated populations. Moreover, genome-wide estimates of nucleotide diversity were virtually identical in F. chiloensis,F. virginiana, and F. × ananassa (π = 0.0059–0.0060). We found, however, that nucleotide diversity and heterozygosity were significantly lower in modern F. × ananassa populations that have experienced significant genetic gains and have produced numerous agriculturally important cultivars.
Patients with cancer appear morevulnerable to SARS-COV-2: A multi-center study during the COVID-19 outbreak
Authors: M. Y. Dai, D. B. Liu, M. Liu, F. X. Zhou, G. L. Li, Z. Chen, Z. A. Zhang, M. Wu, Q. C. Zheng, Y. Xiong, H. H. Xiong, C. Wang, C. C. Chen, F. Xiong, Y. Zhang, Y. Q. Peng, S. P. Ge, B. Zhen, T. T. Yu, L. Wang, H. Wang, Y. Liu, Y. S. Chen, J. Hua Mei, X. J. Gao, Z. Y. Li, L. J. Gan, C. He, Z. Li, Y. Y. Shi, Y. W. Qi, J. Yang, D. G. Tenen, L. Chai, L. A. Mucci, M. Santillana, H. Cai
Journal: Cancer Research (2020)

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020  Given thatpatients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 are needed  We performed a multi-center study including 105 cancer patientsand 536 age-matched non-cancer patients confirmed with COVID-19  Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes  Patients with hematological cancer, lung cancer, or with metastaticcancer (stage IV) had the highest frequency of severe events  Non-metastatic cancer patients experienced similarfrequencies of severe conditions to those observed in patients with zout cancer  Patients who received surgery hadhigher risks of having severe events, while patients with only radiotherapy did not demonstrate significantdifferences in severe events when compared to patients without cancer  These findings indicate that cancer patientsappear more vulnerable to SARS-COV-2 outbreak  Since this is the first large cohort study on this topic, our reportwill provide the much-needed information that will benefit global cancer patients  As such, we believe it is extremelyimportant that our study be disseminated widely to alert clinicians and patients
PD-1 blockade exacerbates <i>Mycobacterium tuberculosis</i> infection in rhesus macaques
Authors: Keith D. Kauffman, Shunsuke Sakai, Nickiana E. Lora, Sivaranjani Namasivayam, Paul J. Baker, Olena Kamenyeva, Taylor W. Foreman, Christine E. Nelson, Deivide Oliveira-de-Souza, Caian L. Vinhaes, Ziv Yaniv, Cecilia S. Lindestam Arleham, Alessandro Sette, Gordon J. Freeman, Rashida Moore, Alan Sher, Katrin D. Mayer-Barber, Bruno B. Andrade, Juraj Kabat, Laura E. Via, Daniel L. Barber
Journal: Science Immunology (2021)

Blockade of the PD-1 coinhibitory pathway compromises immune control of Mycobacterium tuberculosis infection in rhesus macaques.
Chimpanzee Adenovirus Vector Ebola Vaccine — Preliminary Report
Authors: Julie E Ledgerwood, Nancy J Sullivan, Barney S Graham
Journal: New England Journal of Medicine (2015)

Background The unprecedented 2014 epidemic of Ebola virus disease (EVD) has prompted an international response to accelerate the availability of a preventive vaccine. A replicationdefective recombinant chimpanzee adenovirus type 3–vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. Methods We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10 10 particle units or 2×10 11 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 weeks after vaccination. Results In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10 11 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10 11 particle-unit dose than in the group that received the 2×10 10 particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P = 0.001). Glycoproteinspecific T-cell responses were more frequent among those who received the 2x10 11 particle-unit dose than among those who received the 2×10 10 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P = 0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P = 0.07). Conclusions Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×10 11 particle-unit dose, glycoprotein Zaire–specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates. Clinical trials assessing cAd3-EBO are ongoing. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866.)
Endoplasmic reticulum protein TXNDC5 promotes renal fibrosis by enforcing TGF-β signaling in kidney fibroblasts
Authors: Yen-Ting Chen, Pei-Yu Jhao, Chen-Ting Hung, Yueh-Feng Wu, Sung-Jan Lin, Wen-Chih Chiang, Shuei-Liong Lin, Kai-Chien Yang
Journal: Journal of Clinical Investigation (2021)

Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney disease (CKD), often results in diffuse kidney scarring and predisposes to end-stage renal disease. Currently, there is no effective therapy against renal fibrosis. Recently, our laboratory identified an ER-resident protein, thioredoxin domain containing 5 (TXNDC5), as a critical mediator of cardiac fibrosis. Transcriptome analyses of renal biopsy specimens from patients with CKD revealed marked TXNDC5 upregulation in fibrotic kidneys, suggesting a potential role of TXNDC5 in renal fibrosis. Employing multiple fluorescence reporter mouse lines, we showed that TXNDC5 was specifically upregulated in collagen-secreting fibroblasts in fibrotic mouse kidneys. In addition, we showed that TXNDC5 was required for TGF-β1–induced fibrogenic responses in human kidney fibroblasts (HKFs), whereas TXNDC5 overexpression was sufficient to promote HKF activation, proliferation, and collagen production. Mechanistically, we showed that TXNDC5, transcriptionally controlled by the ATF6-dependent ER stress pathway, mediated its profibrogenic effects by enforcing TGF-β signaling activity through posttranslational stabilization and upregulation of type I TGF-β receptor in kidney fibroblasts. Using a tamoxifen-inducible, fibroblast-specific Txndc5 knockout mouse line, we demonstrated that deletion of Txndc5 in kidney fibroblasts mitigated the progression of established kidney fibrosis, suggesting the therapeutic potential of TXNDC5 targeting for renal fibrosis and CKD.
Low prevalence of SARS-COV-2 infection among asymptomatic patients with chronic liver disease in Osaka, Japan
Authors: M. Enomoto, Y. Kido, Y. Nakagama, A. Kaneko, N. Odagiri, K. Yoshida, K. Kotani, H. Motoyama, R. Kozuka, E. Kawamura, A. Hagihara, H. Fujii, S. Uchida, A. Tamori, N. Kawada
Journal: Hepatology (2020)

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become an emerging pandemic threat worldwide The prevalence of SARS-CoV-2 infection is relatively low in Japan;3,269 confirmed cases and 984 deaths were reported as of July 16, 2020 However, prevalence of subclinical SARS-CoV-2 infection remains to be determined In addition, whether it affects the clinical course of chronic liver diseases is still unknown Materials and Methods: A total of 1,462 serum samples were collected from patients without respiratory symptoms who visited outpatient clinic of Department of Hepatology in our hospital: 600 were taken before the SARS-CoV-2 endemic (Jun-Aug 2018 and Dec 2018-Feb 2019) as controls, and 862 were taken after SARSCoV- 2 was identified (Jan-Jun 2020)  Of the 862 patients (63 ± 15 years old, 388 women and 474 men), 137 (15 9%) had HBsAg and 447 (51 9%) had anti-HCV;138 (16 0%) had HCC IgM and IgG antibodies against SARS-CoV-2 were detected in serum by using the SARS-CoV-2 IgM & IgG Quantum Dot Immunoassay (Mokobio Biotechnology R & D Center Inc ) Results: The positive rates of IgM and IgG anti-SARS-CoV-2 throughout the study period are shown in Table Even before the SARS-CoV-2 endemic, IgG anti-SARS-CoV-2 values were positive in 11/600 (1 8%) patients (median 0 16, range 0 10- 1 51), but IgM anti-SARS-CoV-2 were negative in all patients After SARS-CoV-2 identified, IgG anti-SARS-CoV-2 values were positive in 6/300 (2 0%) patients (median 0 26, range 0 14-1 08), and among them, 1/6 (17%) patient was also positive for IgM anti-SARS-CoV-2 (value, 4 38) between Janand Mar 2020 Moreover, between Apr and Jun 2020, IgG anti- SARS-CoV-2 values were positive in 10/562 (1 8%) patients (median 0 27, range 0 12-4 16), and among them, 6/10 (60%) patients was also positive for IgM anti-SARS-CoV-2 (median 0 66, range 0 32-1 36) Of the 7 IgM anti-SARS-CoV-2 positive patients (70 ± 8 years old, 4 women and 3 men), 2 (29%) had HBsAg, 4 (57%) had anti-HCV, and 1 (14%) had autoimmune hepatitis (receiving prednisolone);none had HCC or other types of cancer Comorbidities included hypertension in 2 patients, diabetes in 1 and rheumatoid arthritis in 2 (including 1 receiving prednisolone)  No significant worsening of liver diseases was observed in any patients Conclusion: The false positive rates of IgG anti-SARS-CoV-2 were 1 to 2%, a little higher in patients with chronic liver diseases than the reported rates The results of IgM anti-SARS-CoV-2 testing suggested that subclinical SARS-CoV-2 infection is rare in Osaka, Japan, but the prevalence is increasing over time We found no evidence that subclinical SARS-CoV-2 infection was associated with progression of chronic liver diseases
The use of cabozantinib in advanced hepatocellular carcinoma (HCC): Hong Kong multi-center experience.
Authors: Yawen Dong, Thomas Wai-Tong Leung, Gin Wai Kwok, Vikki Tang, Bryan Li, Roland Ching-Yu Leung, Joanne Wing Yan Chiu, Jeffrey Sum Lung Wong, Ka Wing Ma, Wong Hoi She, Wing Yan Josephine Tsang, Tan To Cheung, Thomas Yau
Journal: Journal of Clinical Oncology (2021)

316 Background: In the phase III CELESTIAL trial, cabozantinib showed significant improvement in overall survival with good tolerability in advanced HCC population. We aimed to evaluate the efficacy, survival and tolerability of cabozatinib in advanced hepatocellular carcinoma (HCC) patients in a real life setting. Methods: Between February 2018 and October 2019, consecutive advanced HCC patients who received cabozatinib alone or in combination at University of Hong Kong Health System hospitals were analysed. Cabozantinib was administered at 60 mg continuously daily. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and tolerability were evaluated. Results: Overall, 22 patients were included. The median age was 57.1 years (range 48.5-58.6). All patients except one were hepatitis B carriers. More than 80% of the patients had underlying Child-Pugh A cirrhosis. Most patients had metastatic disease (95.5%). More than 70% of patients received cabozantinib beyond second-line, and most of the patients had prior exposure to tyrosine kinase inhibitor (TKI) and/or immunotherapy. The median time from the start of first-line systemic treatment to the start of cabozantinib was 11.2 months. Cabozantinib was administered to 11 patients (50%) as single agent, while the other half received cabozantinib in combination with mostly immune checkpoint inhibitors. The median follow-up was 7.6 months. The table below shows the ORR. The overall median TTP and OS were 4.2 and 8.90 months, respectively. Interestingly, among those who received single agent cabozantinib, the median OS was 5.36 months in contrast to 12.32 months in the patients received combination. Overall, 90.9% of patients experienced treatment related adverse events (TRAEs) with transient liver function occurred in nearly 50% patients. Nevertheless, Grade 3/4 TRAEs was only 12%. Conclusions: Our present study showed that the use of cabozatinib in advanced HCC patients had good anti-tumour activity and survival benefits with acceptable toxicity profile. [Table: see text]
Correction to: Extremity soft tissue coverage in the combat zone: use of pedicled flap transfers by the deployed orthopedic surgeon
Authors: Laurent Mathieu, Soryapong Plang, Nicolas de l’Escalopier, James Charles Murison, Christophe Gaillard, Antoine Bertani, Frédéric Rongieras
Journal: Military Medical Research (2021)

An amendment to this paper has been published and can be accessed via the original article.
SARS-CoV-2 Transmission Associated with High School Wrestling Tournaments — Florida, December 2020–January 2021
Authors: Christine Atherstone, Molly Siegel, Emily Schmitt-Matzen, Scott Sjoblom, Joy Jackson, Carina Blackmore, John Neatherlin
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

A used the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW) rapid antigen test in testing for symptomatic persons, with follow-up reverse transcription-polymerase chain reaction (RT-PCR) testing if the antigen test was negative, and RT-PCR testing for all asymptomatic persons; results were considered positive if either the BinaxNOW or RT-PCR test result was positive.Wrestling tournament attendees and contacts were encouraged to seek COVID-19 testing services regardless of symptoms, but the decision to be tested was left to each person.† This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy: 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C.Sect.241(d); 5 U.S.C.Sect.552a; 44 U.S.C.Sect.3501 et seq.§ Four tournament attendees received positive test results during June-November 2020 and were not included in the attack rate calculation.
Incidence and Factors Associated With Acne Among Transgender Patients Receiving Masculinizing Hormone Therapy
Authors: Nick Thoreson, Jason A. Park, Chris Grasso, Jennifer Potter, Dana S. King, Linda G. Marc, Changyu Shen, J. Klint Peebles, Erica D. Dommasch
Journal: JAMA Dermatology (2021)

Acne is a common condition among transgender patients receiving masculinizing hormone therapy (MHT), but the incident risk and predictors of developing acne in this population have not yet been studied on a large scale.To assess risk of acne among a large population of transgender patients receiving MHT and clinical risk factors for acne diagnosis.A retrospective cohort study that included 988 patients who started MHT between January 1, 2014, and December 31, 2017, with at least 1 year of follow-up was performed. Data analysis was conducted from September 1 to 15, 2019. Data were obtained using electronic health records from a community health center serving the sexual and gender minority community. The population included every patient who began receiving MHT during the study period who was aged 18 years or older at the time of MHT initiation and whose assigned sex at birth was female.The main outcome was acne defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for acne. Overall prevalence and incidence proportions over 2 years after initiation of MHT were calculated. Baseline demographic and clinical characteristics were collected at the time of MHT initiation. A series of univariate analyses for all factors was calculated to test for an association with acne diagnosis, followed by multivariate analyses to test for independent predictors.For 988 patients (median age, 25.8 years; interquartile range, 20.8-28.2 years), there was an overall acne prevalence of 31.1% (n = 307). The 1-year post-MHT acne incidence proportion was 19.0% and the 2-year incidence proportion was 25.1%. A younger age at MHT initiation was associated with a higher likelihood of developing acne, with a median of 22.4 years (interquartile range, 19.7-25.6 years) among patients who developed acne vs 24.7 years (interquartile range, 21.3-29.4 years) among patients who did not (P = .002).Acne is a common condition among transgender patients on MHT, with a prevalence increasing from 6.3% to 31.1% following MHT initiation. Patients aged 18 to 21 years appear to be the most likely to develop acne after MHT initiation.
moral heuristics or moral competence? reflections on sunstein
Authors: john mikhail
Journal: Behavioral and Brain Sciences (2005)

by focusing on mistaken judgments, sunstein provides a theory of performance errors without a theory of moral competence. additionally, sunstein's objections to thought experiments like the footbridge and trolley problems are unsound. exotic and unfamiliar stimuli are used in theory construction throughout the cognitive sciences, and these problems enable us to uncover the implicit structure of our moral intuitions.