tbuckley/cabot-search huggingface dataset:
Development and interpretation of a pathomics-based model for the prediction of microsatellite instability in Colorectal Cancer
Authors: Rui Cao, Fan Yang, Si-Cong Ma, Li Liu, Yu Zhao, Yan Li, De-Hua Wu, Tongxin Wang, Wei-Jia Lu, Wei-Jing Cai, Hong-Bo Zhu, Xue-Jun Guo, Yu-Wen Lu, Jun-Jie Kuang, Wen-Jing Huan, Wei-Min Tang, Kun Huang, Junzhou Huang, Jianhua Yao, Zhong-Yi Dong
Journal: Theranostics (2020)

Microsatellite instability (MSI) has been approved as a pan-cancer biomarker for immune checkpoint blockade (ICB) therapy.However, current MSI identification methods are not available for all patients.We proposed an ensemble multiple instance deep learning model to predict microsatellite status based on histopathology images, and interpreted the pathomics-based model with multi-omics correlation.Methods: Two cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from an Asian colorectal cancer (CRC) cohort (Asian-CRC).We established the pathomics model, named Ensembled Patch Likelihood Aggregation (EPLA), based on two consecutive stages: patch-level prediction and WSI-level prediction.The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning.The pathological signatures extracted from the model were analyzed with genomic and transcriptomic profiles for model interpretation. Results:The EPLA model achieved an area-under-the-curve (AUC) of 0.8848 (95% CI: 0.8185-0.9512) in the TCGA-COAD test set and an AUC of 0.8504 (95% CI: 0.7591-0.9323) in the external validation set Asian-CRC after transfer learning.Notably, EPLA captured the relationship between pathological phenotype of poor differentiation and MSI (P < 0.001).Furthermore, the five pathological imaging signatures identified from the EPLA model were associated with mutation burden and DNA damage repair related genotype in the genomic profiles, and antitumor immunity activated pathway in the transcriptomic profiles.Conclusions: Our pathomics-based deep learning model can effectively predict MSI from histopathology images and is transferable to a new patient cohort.The interpretability of our model by association with pathological, genomic and transcriptomic phenotypes lays the foundation for prospective clinical trials of the application of this artificial intelligence (AI) platform in ICB therapy.
Association of Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis With Marked Improvement in Health‐Related Quality of Life
Authors: Nancy Maltez, Mathieu Puyade, Mianbo Wang, Pauline Lansiaux, Zora Marjanovic, Catney Charles, Russell Steele, Murray Baron, Ines Colmegna, Marie Hudson, Dominique Farge
Journal: Arthritis & Rheumatology (2020)

To quantify the magnitude, domains, and duration of change in health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) who underwent autologous hematopoietic stem cell transplantation (HSCT) as compared to SSc patients with similar characteristics who did not undergo autologous HSCT.The study was designed as a retrospective study comparing SSc patients who underwent autologous HSCT and SSc patients who met the criteria for transplantation but were treated with conventional care. Outcomes included scores on the 36-item Short Form (SF-36) health survey and the Health Assessment Questionnaire (HAQ) and its disease-specific symptom scales. Differences in scores between the groups were compared using linear models, adjusting for baseline scores and inverse probability of treatment and censoring weights.In total, 41 SSc patients who underwent autologous HSCT and 65 SSc patients treated with conventional care were compared. In marginal linear weighted models, the SF-36 physical component summary score was a mean ± SEM 7.02 ± 1.94 points higher at the first annual visit (P = 0.001) and 14.40 ± 6.16 points higher at the seventh annual visit (P = 0.03) in patients treated with autologous HSCT compared to the conventional care group. HAQ scores were significantly better in the autologous HSCT group compared to the conventional care group during follow-up (mean ± SEM difference from baseline -0.57 ± 0.13 [P < 0.001] at the first annual visit and -0.94 ± 0.49 [P = 0.07] at the seventh annual visit). There were no differences in the SF-36 mental component summary scores between the 2 groups either at baseline or during follow-up.This study provides robust complementary HRQoL data, including overall and event-free survival data, to expand on the standard repertoire of biomedical variables, thus potentially supporting the physical benefits of autologous HSCT in patients with SSc.
circ-PRKCB acts as a ceRNA to regulate p66Shc-mediated oxidative stress in intestinal ischemia/reperfusion
Authors: Dongcheng Feng, Zhecheng Wang, Yan Zhao, Yang Li, Deshun Liu, Zhao Chen, Shili Ning, Yan Hu, Jihong Yao, Xiaofeng Tian
Journal: Theranostics (2020)

Background: Oxidative stress has emerged as an essential factor in the pathogenesis of intestinal ischemia/reperfusion (I/R) injury. The adaptor protein p66Shc is a key regulator of reactive oxygen species (ROS) generation and a mediator of I/R damage in the intestine, but the upstream mechanisms that directly regulate p66Shc expression during intestinal I/R remain largely unknown. Recent studies have suggested that noncoding RNAs, such as circular RNAs (circRNAs), are important players in physiological and pathological processes based on their versatile regulatory roles in gene expression. The aim of this study was to elucidate the contribution of p66Shc to oxidative damage in intestinal I/R and to investigate the regulation of p66Shc by circRNA sponges. Methods: Intestinal I/R was induced in mice via superior mesenteric artery (SMA) occlusion. A miR-339-5p agomir or circ-protein kinase C beta (PRKCB) siRNA was injected intravenously before I/R challenge. In addition, Caco-2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. Results:In vitro, p66Shc deficiency significantly reduced H/R-induced ROS overproduction by attenuating mitochondrial superoxide anion (O2-) levels, suppressing NADPH oxidase activity and enhancing antioxidant enzyme expression. Moreover, miR-339-5p was identified to directly regulate p66Shc expression in the intestine. Furthermore, we found that a circRNA transcribed from the PRKCB gene, named circ-PRKCB, acted as an endogenous miR-339-5p sponge to regulate p66Shc expression. circ-PRKCB silencing or miR-339-5p overexpression significantly downregulated p66Shc expression and attenuated oxidative stress levels and I/R injury in vivo and in vitro. Notably, the increased circ-PRKCB levels and decreased miR-339-5p levels associated with murine intestinal I/R were consistent with those in patients with intestinal infarction. Conclusions: Our findings reveal a crucial role for the circ-PRKCB/miR-339-5p/p66Shc signaling pathway in regulating oxidative stress in the I/R intestine. This pathway may be a potential therapeutic target for intestinal I/R injury.
Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle
Authors: Christine S. Kim, Xiaolei Ding, Kira Allmeroth, Leah C. Biggs, Olivia I. Kolenc, Nina L’Hoest, Carlos Andrés Chacón-Martínez, Christian Edlich-Muth, Patrick Giavalisco, Kyle P. Quinn, Martin S. Denzel, Sabine A. Eming, Sara A. Wickström
Journal: Cell Metabolism (2020)
AB0159 Joint hypermobility and musculoskeletal pain
Authors: MM Costa, P Nero, E Branco, J Branco
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of this study was analyse the frequency of joint hypermobility in urban schoolchildren and association with musculoskeletal pain. <h3>Methods</h3> The modified criteria of Cartier and Wilkinson for joint hypermobility was applied, by two Rheumatologists, on 479 schoolchildren (263 female and 216 male). Mean age was 11+2.4 years, range 6–17 years. The population was 92% Caucasian. All children answered a questionnaire for musculoskeletal pain. <h3>Results</h3> Forty one percent had one of the five positive test manoeuvres for joint hypermobility. Only one child had 3 positive test manoeuvres, 20 had two positive test and 175 had one positive test manoeuvres (mean 1.1 +0.3). Passive apposition of the thumbs to the flexor aspects of the forearm occurred in 168 cases. Musculoskeletal pain occurred in 32% of children, without relationship of pain and hypermobility in the same joint. Presence of pain was no statistically significant among cases with and without hypermobility. Physical activity was no associated with pain in hypermobility joint. <h3>Conclusion</h3> Hypermobility syndrome was rare in our population. Passive apposition of the thumbs to the flexor aspects of the forearm was the most frequent positive manover. Joint hypermobility was no related with musculoskeletal pain. Physical activity was no a risk factor to pain in joint with hyperlaxity.
M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation
Authors: Wenhua Yan, Tianhan Li, Tieying Yin, Zhengjun Hou, Kai Qu, Nan Wang, Colm Durkan, Lingqing Dong, Juhui Qiu, Hans Gregersen, Guixue Wang
Journal: Theranostics (2020)

Rationale: For intravascular stent implantation to be successful, the processes of vascular tissue repair and therapy are considered to be critical. However, the mechanisms underlying the eventual fate of vascular smooth muscle cells (VSMCs) during vascular tissue repair remains elusive. In this study, we hypothesized that M2 macrophage-derived exosomes to mediate cell-to-cell crosstalk and induce dedifferentiation phenotypes in VSMCs. Methods:In vivo, 316L bare metal stents (BMS) were implanted from the left iliac artery into the abdominal aorta of 12-week-old male Sprague-Dawley (SD) rats for 7 and 28 days. Hematoxylin and eosin (HE) were used to stain the neointimal lesions. En-face immunofluorescence staining of smooth muscle 22 alpha (SM22α) and CD68 showed the rat aorta smooth muscle cells (RASMCs) and macrophages. Immunohistochemical staining of total galactose-specific lectin 3 (MAC-2) and total chitinase 3-like 3 (YM-1) showed the total macrophages and M2 macrophages. In vitro, exosomes derived from IL-4+IL-13-treated macrophages (M2Es) were isolated by ultracentrifugation and characterized based on their specific morphology. Ki-67 staining was conducted to assess the effects of the M2Es on the proliferation of RASMCs. An atomic force microscope (AFM) was used to detect the stiffness of the VSMCs. GW4869 was used to inhibit exosome release. RNA-seq was performed to determine the mRNA profiles of the RASMCs and M2Es-treated RASMCs. Quantitative real-time PCR (qRT-PCR) analysis was conducted to detect the expression levels of the mRNAs. Western blotting was used to detect the candidate protein expression levels. T-5224 was used to inhibit the DNA binding activity of AP-1 in RASMCs. Results: M2Es promote c-KIT expression and softening of nearby VSMCs, hence accelerating the vascular tissue repair process. VSMCs co-cultured in vitro with M2 macrophages presented an increased capacity for de-differentiation and softening, which was exosome dependent. In addition, the isolated M2Es helped to promote VSMC dedifferentiation and softening. Furthermore, the M2Es enhanced vascular tissue repair potency by upregulation of VSMCs c-KIT expression via activation of the c-Jun/activator protein 1 (AP-1) signaling pathway.Conclusions: The findings of this study emphasize the prominent role of M2Es during VSMC dedifferentiation and vascular tissue repair via activation of the c-Jun/AP-1 signaling pathway, which has a profound impact on the therapeutic strategies of coronary stenting techniques.
Appraisal and revalidation for UK doctors—time to assess the evidence
Authors: Victoria Tzortziou Brown, Margaret McCartney, Carl Heneghan
Journal: BMJ (2020)

Appraisal is the product of two determining discourses: regulation and professionalism.It aims to respond to distinct, often competing priorities which require different processes.• There is currently little evidence of appraisal achieving its objectives which range from assuring a doctor's fitness to practise and performance management, to driving personal and professional development whilst providing coaching, mentoring and pastoral care.• The pause of appraisal and revalidation during the pandemic offers an opportunity for clarification of its purpose.This should be followed by research to identify the appropriate intervention tools and outcomes, measurement of intended and unintended consequences, and evaluation of cost-effectiveness.
Treatment and Control of Hypertension in 2020
Authors: Gregory Curfman, Howard Bauchner, Philip Greenland
Journal: JAMA (2020)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Importance of Careful Patient Selection in the Use of Follow-up Bone Mineral Density Testing
Authors: Douglas C. Bauer
Journal: JAMA Internal Medicine (2020)

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
Sebaceous Carcinoma Epidemiology and Genetics: Emerging Concepts and Clinical Implications for Screening, Prevention, and Treatment
Authors: Michael R. Sargen, Gabriel J. Starrett, Eric A. Engels, Elizabeth K. Cahoon, Margaret A. Tucker, Alisa M. Goldstein
Journal: Clinical Cancer Research (2020)

Sebaceous carcinoma is an aggressive skin cancer with a 5-year overall survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been increasing in the United States for several decades, but the underlying reasons for this increase are unclear. In this article, we review the epidemiology and genetics of sebaceous carcinoma, including recent population data and tumor genomic analyses that provide new insights into underlying tumor biology. We further discuss emerging evidence of a possible viral etiology for this cancer. Finally, we review the clinical implications of recent advances in sebaceous carcinoma research for screening, prevention, and treatment.
Challenges in Prediction and Diagnosis of Alcohol Withdrawal Syndrome and Wernicke Encephalopathy—Reply
Authors: Thomas D. Brothers, Paxton Bach
Journal: JAMA Internal Medicine (2020)

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
Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma
Authors: Heimo Breiteneder, Ya‐Qi Peng, Ioana Agache, Zuzana Diamant, Thomas Eiwegger, Wytske J. Fokkens, Claudia Traidl‐Hoffmann, Kari Nadeau, Robyn E. O'Hehir, Liam O'Mahony, Oliver Pfaar, Maria J. Torres, De‐Yun Wang, Luo Zhang, Cezmi A. Akdis
Journal: Allergy (2020)

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.
Psychiatry’s Myopia—Reclaiming the Social, Cultural, and Psychological in the Psychiatric Gaze
Authors: Joel T. Braslow, John S. Brekke, Jeremy Levenson
Journal: JAMA Psychiatry (2020)

This Viewpoint proposes that psychiatry should more closely attend to the poverty, justice system involvement, and housing issues of people with serious mental illness, supporting this view with quotes from philosophers.
Treatment of Hemophilia — More Amazing Progress
Authors: Pier M. Mannucci
Journal: New England Journal of Medicine (2020)

With a prevalence of 17.1 cases per 100,000 males, hemophilia A is the most frequent inherited disorder of blood coagulation.1 After the adoption of prophylactic replacement therapy with factor VIII administered intravenously 3 or 4 times per week, patients' life expectancy has become very close to that of unaffected males.1 Moreover, the occurrence of spontaneous bleeding and the development of musculoskeletal damage have been minimized. In addition, in the past decade, further impressive advances have occurred.2,3 The arrival of factor VIII products with an extended plasma half-life has meant that intravenous injections that are needed to minimize bleeding can be . . .
Prophylactic Donor Lymphocyte Infusions after Haploidentical Hematopoietic Stem Cell Transplantation for High Risk Hematological Malignancies: A Retrospective Bicentric Analysis of Serial Infusions of Increasing Doses of CD3+ Cells
Authors: Raphaël Cauchois, Luca Castagna, Samia Harbi, Boris Calmels, Stefania Bramanti, Angela Granata, Claude Lemarie, Valerio Maisano, Faezeh Legrand, Sabine Furst, Pierre Jean Weiller, Christian Chabannon, Didier Blaise, Raynier Devillier
Journal: Blood (2017)
There is more to pain than tissue damage: eight principles to guide care of acute non-traumatic pain in sport
Authors: J P Caneiro, Rafael Krasic Alaiti, Leandro Fukusawa, Luiz Hespanhol, Peter Brukner, Peter PB O'Sullivan
Journal: British Journal of Sports Medicine (2020)

Musculoskeletal pain in athletes is common, but not always associated with injury (ie, tissue damage).1 Damage occurs when load exceeds tissue tolerance, such as ligament tear or a fracture. However, pain in athletes that occurs in the absence of trauma and tissue damage is still often labelled an 'injury' by clinicians, coaches and athletes themselves. This highlights a gap between knowledge (tissue damage is not necessary for pain) and practice (assuming that all pain arises from tissue damage) in our clinical community.1 2 This applies particularly in the area of acute non-traumatic pain (such as back and joint pain). To help bridge this gap, we outline eight principles to guide clinicians who manage musculoskeletal pain in sport (see infographic in figure 1). Figure 1 Infographic—principles to guide care of acute non-traumatic pain in sport. ### 1. In the absence of trauma, do not assume that pain indicates tissue damage