tbuckley/cabot-search huggingface dataset:
B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse
Authors: Tomoko Ichiyanagi, Hirokazu Katoh, Yoshinobu Mori, Keigo Hirafuku, Beverly Ann Boyboy, Masaki Kawase, Kenji Ichiyanagi
Journal: Molecular Biology and Evolution (2021)

Abstract More than one million copies of short interspersed elements (SINEs), a class of retrotransposons, are present in the mammalian genomes, particularly within gene-rich genomic regions. Evidence has accumulated that ancient SINE sequences have acquired new binding sites for transcription factors (TFs) through multiple mutations following retrotransposition, and as a result have rewired the host regulatory network during the course of evolution. However, it remains unclear whether currently active SINEs contribute to the expansion of TF binding sites. To study the mobility, expression, and function of SINE copies, we first identified about 2,000 insertional polymorphisms of SINE B1 and B2 families within Mus musculus. Using a novel RNA sequencing method designated as melRNA-seq, we detected the expression of SINEs in male germ cells at both the subfamily and genomic copy levels: the vast majority of B1 RNAs originated from evolutionarily young subfamilies, whereas B2 RNAs originated from both young and old subfamilies. DNA methylation and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses in liver revealed that polymorphic B2 insertions served as a boundary element inhibiting the expansion of DNA hypomethylated and histone hyperacetylated regions, and decreased the expression of neighboring genes. Moreover, genomic B2 copies were enriched at the boundary of various histone modifications, and chromatin insulator protein, CCCTC-binding factor, a well-known chromatin boundary protein, bound to &amp;gt;100 polymorphic and &amp;gt;10,000 non-polymorphic B2 insertions. These results suggest that the currently active B2 copies are mobile boundary elements that can modulate chromatin modifications and gene expression, and are likely involved in epigenomic and phenotypic diversification of the mouse species.
Residual cyclegan for robust domain transformation of histopathological tissue slides
Authors: Thomas de Bel, John-Melle Bokhorst, Jeroen van der Laak, Geert Litjens
Journal: Medical Image Analysis (2021)

Variation between stains in histopathology is commonplace across different medical centers. This can have a significant effect on the reliability of machine learning algorithms. In this paper, we propose to reduce performance variability by using -consistent generative adversarial (CycleGAN) networks to remove staining variation. We improve upon the regular CycleGAN by incorporating residual learning. We comprehensively evaluate the performance of our stain transformation method and compare its usefulness in addition to extensive data augmentation to enhance the robustness of tissue segmentation algorithms. Our steps are as follows: first, we train a model to perform segmentation on tissue slides from a single source center, while heavily applying augmentations to increase robustness to unseen data. Second, we evaluate and compare the segmentation performance on data from other centers, both with and without applying our CycleGAN stain transformation. We compare segmentation performances in a colon tissue segmentation and kidney tissue segmentation task, covering data from 6 different centers. We show that our transformation method improves the overall Dice coefficient by 9% over the non-normalized target data and by 4% over traditional stain transformation in our colon tissue segmentation task. For kidney segmentation, our residual CycleGAN increases performance by 10% over no transformation and around 2% compared to the non-residual CycleGAN.
KPT-330 Prevents Aortic Valve Calcification via a Novel C/EBPβ Signaling Pathway
Authors: Punashi Dutta, Karthik M. Kodigepalli, Stephanie LaHaye, J. Will Thompson, Sarah Rains, Casey Nagel, Kaitlyn Thatcher, Robert B. Hinton, Joy Lincoln
Journal: Circulation Research (2021)

[Figure: see text].
Abstract 16074: Cellular Immune Activation and Breastfeeding in Peripartum Cardiomyopathy
Authors: Agnes Koczo, Amy Marino, Arun Jeyabalan, Uri Elkayam, Leslie Cooper, James Fett, Charles McTiernan, Penelope Morel, Karen Hanley-Yanez, Dennis McNamara
Journal: Circulation (2017)

Background: Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. An autoimmune etiology has been postulated. Prolactin elevation in the early peripartum perio...
Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation
Authors: Jianing Fu, Julien Zuber, Brittany Shonts, Aleksandar Obradovic, Zicheng Wang, Kristjana Frangaj, Wenzhao Meng, Aaron M. Rosenfeld, Elizabeth E. Waffarn, Peter Liou, Sai-ping Lau, Thomas M. Savage, Suxiao Yang, Kortney Rogers, Nichole M. Danzl, Shilpa Ravella, Prakash Satwani, Alina Iuga, Siu-hong Ho, Adam Griesemer, Yufeng Shen, Eline T. Luning Prak, Mercedes Martinez, Tomoaki Kato, Megan Sykes
Journal: Journal of Clinical Investigation (2021)

In humans receiving intestinal transplantation (ITx), long-term multilineage blood chimerism often develops. Donor T cell macrochimerism (≥4%) frequently occurs without graft-versus-host disease (GVHD) and is associated with reduced rejection. Here we demonstrate that patients with macrochimerism had high graft-versus-host (GvH) to host-versus-graft (HvG) T cell clonal ratios in their allografts. These GvH clones entered the circulation, where their peak levels were associated with declines in HvG clones early after transplant, suggesting that GvH reactions may contribute to chimerism and control HvG responses without causing GVHD. Consistently, donor-derived T cells, including GvH clones, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were simultaneously detected in the recipients’ BM more than 100 days after transplant. Individual GvH clones appeared in ileal mucosa or PBMCs before detection in recipient BM, consistent with an intestinal mucosal origin, where donor GvH-reactive T cells expanded early upon entry of recipient APCs into the graft. These results, combined with cytotoxic single-cell transcriptional profiles of donor T cells in recipient BM, suggest that tissue-resident GvH-reactive donor T cells migrated into the recipient circulation and BM, where they destroyed recipient hematopoietic cells through cytolytic effector functions and promoted engraftment of graft-derived HSPCs that maintain chimerism. These mechanisms suggest an approach to achieving intestinal allograft tolerance.
Abstract 11888: Considerable Burdens of Excessive Deaths, Myocardial Infarction, Stroke, Heart Failure and Kidney Replacement Therapy Due to Mild to Moderately Reduced Kidney Function
Authors: Masaki Ohsawa, Kozo Tanno, Kazuyoshi Itai, Kuniaki Ogasawara, Wataru Obara, Yuki Yonekura, Yoshihiro Morino, Tomonori Itoh, So Omori, Takaya Abe, Shinichi Omama, Yasuhiro Ishibashi, Toru Kuribayashi, Shuko Takahashi, Akira Okayama
Journal: Circulation (2018)

Introduction: Chronic kidney disease (CKD) contributes to not only an increased risk of end-stage renal disease (ESRD) but also increased risks of premature death and cardiovascular diseases. To wh...
Squamous Cell Carcinoma Mimicking Neck Paraganglioma on 68Ga-DOTATATE PET/CT
Authors: Caner Civan, Emine Goknur Isik, Duygu Has Simsek, Comert Sen, Seher Nilgun Unal
Journal: Clinical Nuclear Medicine (2021)

Somatostatin receptor (SSTR) imaging with 68Ga-labeled somatostatin analogs has been used for many tumors with high SSTR expression. Increased uptake mostly depends on the SSTR status of tumors; however, false-positive uptake can be demonstrated in benign diseases or other malignancies because of the increased SSTR expression. We present a case of a 50-year-old man with increased SSTR activity on cervical lesion located in internal jugular chain in 68Ga-DOTATATE PET/CT, which was performed for suspicion of paraganglioma. Biopsy revealed lymph node metastasis of squamous cell carcinoma other than paraganglioma. 18F-FDG PET/CT showed primary malignancy on larynx and lymph node metastasis, which were correlated surgically.
Transpupillary collagen photocrosslinking for targeted modulation of ocular biomechanics
Authors: B.G. Gerberich, B.G. Hannon, A. Hejri, E.J. Winger, E. Schrader Echeverri, L.M. Nichols, H.G. Gersch, N.A. MacLeod, S. Gupta, A.T. Read, M.D. Ritch, S. Sridhar, M.G. Toothman, G.S. Gershon, S.A. Schwaner, G. Sánchez-Rodríguez, V. Goyal, A.M. Toporek, A.J. Feola, H.E. Grossniklaus, M.T. Pardue, C.R. Ethier, M.R. Prausnitz
Journal: Biomaterials (2021)
Ecto-GPR37: a potential biomarker for Parkinson’s disease
Authors: Xavier Morató, Paula Garcia-Esparcia, Josep Argerich, Franc Llorens, Inga Zerr, Wojciech Paslawski, Eva Borràs, Eduard Sabidó, Ulla E. Petäjä-Repo, Víctor Fernández-Dueñas, Isidro Ferrer, Per Svenningsson, Francisco Ciruela
Journal: Translational Neurodegeneration (2021)

Abstract Objective α-Synuclein has been studied as a potential biomarker for Parkinson’s disease (PD) with no concluding results. Accordingly, there is an urgent need to find out reliable specific biomarkers for PD. GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism. Here, we investigated whether GPR37 is upregulated in sporadic PD, and thus a suitable potential biomarker for PD. Methods GPR37 protein density and mRNA expression in postmortem substantia nigra (SN) from PD patients were analysed by immunoblot and RT-qPCR, respectively. The presence of peptides from the N-terminus-cleaved domain of GPR37 (i.e. ecto-GPR37) in human cerebrospinal fluid (CSF) was determined by liquid chromatography-mass spectrometric analysis. An engineered in-house nanoluciferase-based immunoassay was used to quantify ecto-GPR37 in CSF samples from neurological control (NC) subjects, PD patients and Alzheimer’s disease (AD) patients. Results GPR37 protein density and mRNA expression were significantly augmented in sporadic PD. Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method. However, the CSF total α-synuclein level in PD patients did not differ from that in NC subjects. Similarly, the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered. Conclusion GPR37 expression is increased in SN of sporadic PD patients. The ecto-GPR37 peptides are significantly increased in the CSF of PD patients, but not in AD patients. These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.
Placebo—The Unknown Variable in a Controlled Trial
Authors: Maryanne Demasi, Tom Jefferson
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
Reply: Is high-dose glucocorticoid beneficial in COVID-19?
Authors: Maryam Edalatifard, Maryam Akhtari, Mohammadreza Salehi, Elham Farhadi, Ahmadreza Jamshidi, Mahdi Mahmoudi, Abdolrahman Rostamian
Journal: European Respiratory Journal (2021)

In their correspondence, V. Muthu and co-workers raise some issues related to our recent clinical trial "Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial" [1]. This provides a welcome opportunity to further explain the outcome of using a high dose of glucocorticoid for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Our clinical trial supports the beneficial use of a high dose of methylprednisolone for the treatment of severe COVID-19 patients. <https://bit.ly/3qvc4Kz>
Abstract PS5-39: Tumour cellularity size as a biomarker to predict response after <i>neoadjuvant endocrine therapy</i>: Correlation analysis between Ki67 expression and PEPI score
Authors: Joanna Ines Lopez Velazco, María Otaño, Lide Larburu, Ainhara Lahuerta, Kepa Elorriaga, Virginia Segur, Juan Carlos Irizabal, Ana Martínez, Lourdes Jáuregui, Maria M. Caffarel, Ander Urruticoechea
Journal: Cancer Research (2021)

Abstract Background: Neoadjuvant endocrine therapy (NET) is an approach that allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. This evaluation is mainly performed in surgical specimens after NET and it has been used as a research tool to obtain prognostic and predictive information using tumour response to decide adjuvant treatment. In this setting, there are not many validated biomarkers to predict response beyond Ki67 expression and Preoperative Prognostic Index (PEPI score) in NET. The aim of this study is to determine if the tumour cellularity size (TCS) in surgical specimen after NET correlates with PEPI score and Ki67 expression. Methods: Retrospective study of postmenopausal patients with estrogen receptor (ER) positive/HER2 negative resectable breast cancer, treated with an aromatase inhibitor for at least 4 months prior to surgery. Pathological characterization of tumour specimens: Evaluation of the percentage of residual tumour cellularity of formalin fixed paraffin embedded surgical specimens and immunohistochemistry characterization of ER and Ki67. Tumour cellularity size: calculated by combining the percentage of residual tumour cellularity and tumour pathological size. Results: N=104. Tumour characteristics at surgery and breakdown for the calculated PEPI score: table 1. Correlation between the percentage of Ki67 positive cells at surgery and TCS: (r=0.2503) p=0.04 (95% CI, 0.0014 to 0.4700). Correlation between TCS and PEPI score: (r=0.2582) p=0.05 (95% CI, -0.0131 to 0.4940). Conclusions: Tumour cellularity size is a promising biomarker to determine response and prognosis after NET. There is a need to find other biomarkers to predict response after NET. Table 1Pathology/Biomarker statusPEPI score RFS pointsNo. of patientspTNot available (NA)1pT1/T20102pT3/T431pNNA7Negative075Positive322KI67 levelNA10%-2.7%039&amp;gt;2.7%-7.3%131&amp;gt;7.3%-19.7%119&amp;gt;19.7%-53.1%213&amp;gt;53.1%31ER-status Allred scoreNA120-2303-8092PEPI scoreNA190281342533495561PEPI groupNot calculated19I (0 score)28II (1-3 score)42III (≥4 score)15 Citation Format: Joanna Ines Lopez Velazco, María Otaño, Lide Larburu, Ainhara Lahuerta, Kepa Elorriaga, Virginia Segur, Juan Carlos Irizabal, Ana Martínez, Lourdes Jáuregui, Maria M. Caffarel, Ander Urruticoechea. Tumour cellularity size as a biomarker to predict response after neoadjuvant endocrine therapy: Correlation analysis between Ki67 expression and PEPI score [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-39.
Research gaps in medical treatment of transgender/nonbinary people
Authors: Joshua D. Safer
Journal: Journal of Clinical Investigation (2021)

With the growing number of transgender and gender-nonbinary individuals who are becoming visible, it is clear that there is a need to develop a rigorous evidence base to inform care practice. Transgender health research is often limited to HIV/AIDS or mental health research and is typically subsumed in larger studies with general LGBTQ focus. Although the number of knowledgeable health care providers remains modest, the model for the medical approach to transgender health is shifting owing to growing social awareness and an appreciation of a biological component. Gender-affirming medicine facilitates aligning the body of the transgender person with the gender identity; typical treatment regimens include hormone therapy and/or surgical interventions. While broadly safe, hormone treatments require some monitoring for safety. Exogenous estrogens are associated with a dose-dependent increase in venous thromboembolic risk, and androgens stimulate erythropoiesis. The degree to which progressing gender-affirming hormone treatment changes cancer risk, cardiac heart disease risk, and/or bone health remains unknown. Guidelines referencing the potential exacerbation of cancer, heart disease, or other disease risk often rely on physiology models, because conclusive clinical data do not exist. Dedicated research infrastructure and funding are needed to address the knowledge gap in the field.
I Left Vertebral Artery with a Proximal Stenotic Origin and Clinical Implications
Authors: Olutayo Ariyo
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Even though most vertebral artery anomalies are asymptomatic, but the normally arising vertebral artery from the superoposterior surface of its ipsilateral subclavian artery, plays a vital role, via the Subclavian Steal Syndrome to help in vascularization of its ipsilateral upper limb anatomical structures. The case of a left vertebral artery with a proximal origin stenosis in the left limb of a 72 year -old female cadaver is reported and its pathophysiological consequences of the stenosis in an hypothesized proximal occlusion in ipsilateral subclavian artery considered. The left vertebral artery originated normally from the superior -posterior surface of the left subclavian artery, but with a proximal stenotic origin in its proximal 1-1/2mm length. The LVA was of a good caliber size distal to the stenotic segment, proceeding in its pre-foraminal segment superiorly, entering normally the 6th transverse cervical foraminal to begin its osseous path. Proximal stenosis of the vertebral artery are uncommon, but this tends to have a deleterious effect on the posterior circulation in the brain depending on the severity of such stenosis. Stenosis although most frequent in the artery’s 1st part tends to have more deleterious effect with Knowledge of vertebral artery pathologies, its variant origins, lumen size, are important to Head and Neck, Neurosurgeons, Interventional Neuroradiologists in the choice of appropriate surgical and medical managements and to neuroradiologists in the interpretation of images.
Global deletion of NTPDase3 protects against diet-induced obesity by increasing basal energy metabolism
Authors: Bynvant Sandhu, Maria C. Perez-Matos, Stephanie Tran, Garima Singhal, Ismail Syed, Linda Feldbrügge, Shuji Mitsuhashi, Julie Pelletier, Jinhe Huang, Yusuf Yalcin, Eva Csizmadia, Shilpa Tiwari-Heckler, Keiichi Enjyoji, Jean Sévigny, Eleftheria Maratos-Flier, Simon C. Robson, Z. Gordon Jiang
Journal: Metabolism (2021)
Thomas Acheson Harden Carter
Authors: Malcolm McWhirter, Romilly Carter
Journal: BMJ (2021)

After graduating Thomas Acheson Harden Carter (“Harden”) gained his membership of the Royal College of Physicians, worked in paediatrics in New Zealand, returned to Scotland to train in general practice (gaining membership of the Royal College of GPs), and then began training in public health. He won the prestigious Littlejohn Gairdner prize before starting his first consultant appointment.

Harden Carter was a highly esteemed consultant in public health and worked in three adjacent Scottish health boards: Fife, Forth Valley, and Lothian. He drew on his qualifications and experience in general medicine and general practice in a highly productive public health career. His research and publication record was remarkable among his peers.

He worked closely and effectively with clinicians, patients, and managers to develop innovative services well ahead of their time. An early example was …
Combination Therapies for Erectile Dysfunction—A Synergy of Modalities Holds the Key
Authors: John F. Sullivan, Kevin J. Campbell, Larry I. Lipshultz
Journal: JAMA Network Open (2021)

Ioannis Mykoniatis, MD, MSc; Nikolaos Pyrgidis, MD, MSc; Ioannis Sokolakis, MD, MSc, PhD; Andreas Ouranidis, PhD; Petros Sountoulides, MD, MSc, PhD; Anna-Bettina Haidich, PhD; Koenraad van Renterghem, MD, PhD; Georgios Hatzichristodoulou, MD, PhD; Dimitrios Hatzichristou, MD, PhD
Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung
Authors: Elizabeth Dudnik, Samuel Kareff, Mor Moskovitz, Chul Kim, Stephen V Liu, Anastasiya Lobachov, Teodor Gottfried, Damien Urban, Alona Zer, Ofer Rotem, Amir Onn, Mira Wollner, Jair Bar
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Little is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC). Methods 125 consecutive patients with aLCNEC were identified in the electronic databases of 4 participating cancer centers. The patients were divided into group A (patients who received ICI, n=41) and group B (patients who did not receive ICI, n=84). Overall survival since advanced disease diagnosis (OS DX) and OS since ICI initiation (OS ICI) were captured. Results With a median follow-up of 11.8 months (mo) (IQR 7.5–17.9) and 6.0mo (IQR 3.1–10.9), 66% and 76% of patients died in groups A and B, respectively. Median OS DX was 12.4mo (95% CI 10.7 to 23.4) and 6.0mo (95% CI 4.7 to 9.4) in groups A and B, respectively (log-rank test, p=0.02). For ICI administration, HR for OS DX was 0.59 (95% CI 0.38 to 0.93, p=0.02—unadjusted), and 0.58 (95% CI 0.34 to 0.98, p=0.04—adjusted for age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), presence of liver metastases and chemotherapy administration). In a propensity score matching analysis (n=74; 37 patients in each group matched for age and ECOG PS), median OS DX was 12.5 mo (95% CI 10.6 to 25.2) and 8.4 mo (95% CI 5.4 to 16.9) in matched groups A and B, respectively (log-rank test, p=0.046). OS ICI for patients receiving ICI as monotherapy (n=36) was 11.0 mo (95% CI 6.1 to 19.4). Conclusions With the limitations of retrospective design and small sample size, the results of this real-world cohort analysis suggest a positive impact of ICI on OS in aLCNEC.
Identification of a new orthonairovirus associated with human febrile illness in China
Authors: Jun Ma, Xiao-Long Lv, Xu Zhang, Shu-Zheng Han, Ze-Dong Wang, Liang Li, He-Ting Sun, Li-Xin Ma, Zheng-Lei Cheng, Jian-Wei Shao, Chen Chen, Ying-Hua Zhao, Liyan Sui, Lin-Na Liu, Jun Qian, Wei Wang, Quan Liu
Journal: Nature Medicine (2021)
Caution With Routine Use of Daratumumab for Newly Diagnosed High-Risk Multiple Myeloma—Reply
Authors: Smith Giri, Susan Bal, Luciano J. Costa
Journal: JAMA Oncology (2021)

In Reply We thank Mohyuddin et al for their thoughtful comments. They compare our findings on newly diagnosed patients with high-risk multiple myeloma (HRMM)1 to 2 similar meta-analyses.2,3 These studies were published shortly before ours and therefore were not discussed in our article.
Huang X, Kushekhar K, Nolte I, Kooistra W, Visser L, Bouwman I, Kouprie N, Veenstra R, van Imhoff G, Olver B, Houlston RS, Poppema S, Diepstra A, Hepkema B, van den Berg A. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups. Blood. 2011;118(19):5211–5217.
Journal: Blood (2012)