tbuckley/cabot-search huggingface dataset:
Association predictions of genomics, proteinomics, transcriptomics, microbiome, metabolomics, pathomics, radiomics, drug, symptoms, environment factor, and disease networks: A comprehensive approach
Authors: Yi Pan, Xiujuan Lei, Yuchen Zhang
Journal: Medicinal Research Reviews (2021)

Currently, the research of multi-omics, such as genomics, proteinomics, transcriptomics, microbiome, metabolomics, pathomics, and radiomics, are hot spots. The relationship between multi-omics data, drugs, and diseases has received extensive attention from researchers. At the same time, multi-omics can effectively predict the diagnosis, prognosis, and treatment of diseases. In essence, these research entities, such as genes, RNAs, proteins, microbes, metabolites, pathways as well as pathological and medical imaging data, can all be represented by the network at different levels. And some computer and biology scholars have tried to use computational methods to explore the potential relationships between biological entities. We summary a comprehensive research strategy, that is to build a multi-omics heterogeneous network, covering multimodal data, and use the current popular computational methods to make predictions. In this study, we first introduce the calculation method of the similarity of biological entities at the data level, second discuss multimodal data fusion and methods of feature extraction. Finally, the challenges and opportunities at this stage are summarized. Some scholars have used such a framework to calculate and predict. We also summarize them and discuss the challenges. We hope that our review could help scholars who are interested in the field of bioinformatics, biomedical image, and computer research.
Typical Electrocardiogram Pattern Unmasks Atypical Cause of Muscle Weakness
Authors: Guoliang Li, Manyun Tang, Yang Yan
Journal: JAMA Internal Medicine (2021)

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Abstract 14852: Ideal Healthy Lifestyle Components for the Prevention of Atrial Fibrillation in a Community-Based Cohort Study With a 14-Year Follow-Up: The Suita Study
Authors: Yoshihiro Kokubo, Makoto Watanabe, Aya Higashiyama, Yoko M Nakao, Yoshihiro Miyamoto
Journal: Circulation (2018)

Introduction: Few cohort studies of the relationship between lifestyle — especially diet and physical activity (PA) — and incident atrial fibrillation (AF) and no studies of the association between...
OLGIM staging and proton pump inhibitor use predict the risk of gastric cancer
Authors: Junya Arai, Ryota Niikura, Yoku Hayakawa, Tomonori Aoki, Atsuo Yamada, Takashi Kawai, Mitsuhiro Fujishiro
Journal: Gut (2021)

We read with great interest the recent publication written by Lee et al 1 in which the authors conducted a prospective, longitudinal and multicentre study to evaluate the association between intestinal metaplasia (IM) and gastric cancer (GC). As expected, IM was found to be a significant risk factor for GC (adjusted HR (aHR) 5.46; 95% CI 1.51 to 19.0). Nevertheless, operative link on gastric IM (OLGIM) staging was more closely correlated with the risk of GC (stage III/IV; aHR 20.7; 95% CI 5.04 to 85.6, and stage II; aHR 7.34; 95% CI 1.60 to 33.7). They concluded that risk stratification of GC based on OLGIM staging was useful for endoscopic surveillance.

We agree with their results that OLGIM staging is the most important predictor for GC, although there are many other risk factors of GC. According …
Different responses of the oral, nasal and lung microbiomes to cigarette smoke
Authors: Stefan Pfeiffer, Christian Herzmann, Karoline I Gaede, Draginja Kovacevic, Susanne Krauss-Etschmann, Michael Schloter
Journal: Thorax (2021)

To examine the role of smoking on the bacterial community composition of the upper and the lower respiratory tract, a monocentric, controlled prospective study was performed, including healthy smokers, ex-smokers and never-smokers. Smokers were further grouped according to their smoking history. Bacterial diversity was analysed using a molecular barcoding approach based on directly extracted DNA. Our study shows for the first time distinct bacterial response patterns in the upper and lower respiratory tract to cigarette smoking leading to a higher abundance of opportunistic pathogens. The clinical significance of these dysbioses for health needs to be further explored.
Preclinical models of arthritis for studying immunotherapy and immune tolerance
Authors: Gavin R Meehan, Ranjeny Thomas, Shaima Al Khabouri, Pascale Wehr, Catharien MU Hilkens, David C Wraith, Daniela Sieghart, Michael Bonelli, György Nagy, Paul Garside, David F Tough, Huw D Lewis, James M Brewer
Journal: Annals of the Rheumatic Diseases (2021)

Increasingly earlier identification of individuals at high risk of rheumatoid arthritis (RA) (eg, with autoantibodies and mild symptoms) improves the feasibility of preventing or curing disease. The use of antigen-specific immunotherapies to reinstate immunological self-tolerance represent a highly attractive strategy due to their potential to induce disease resolution, in contrast to existing approaches that require long-term treatment of underlying symptoms. Preclinical animal models have been used to understand disease mechanisms and to evaluate novel immunotherapeutic approaches. However, models are required to understand critical processes supporting disease development such as the breach of self-tolerance that triggers autoimmunity and the progression from asymptomatic autoimmunity to joint pain and bone loss. These models would also be useful in evaluating the response to treatment in the pre-RA period. This review proposes that focusing on immune processes contributing to initial disease induction rather than end-stage pathological consequences is essential to allow development and evaluation of novel immunotherapies for early intervention. We will describe and critique existing models in arthritis and the broader field of autoimmunity that may fulfil these criteria. We will also identify key gaps in our ability to study these processes in animal models, to highlight where further research should be targeted.
Chimeric non-antigen receptors in T cell-based cancer therapy
Authors: Jitao Guo, Andrew Kent, Eduardo Davila
Journal: Journal for ImmunoTherapy of Cancer (2021)

Adoptively transferred T cell-based cancer therapies have shown incredible promise in treatment of various cancers. So far therapeutic strategies using T cells have focused on manipulation of the antigen-recognition machinery itself, such as through selective expression of tumor-antigen specific T cell receptors or engineered antigen-recognition chimeric antigen receptors (CARs). While several CARs have been approved for treatment of hematopoietic malignancies, this kind of therapy has been less successful in the treatment of solid tumors, in part due to lack of suitable tumor-specific targets, the immunosuppressive tumor microenvironment, and the inability of adoptively transferred cells to maintain their therapeutic potentials. It is critical for therapeutic T cells to overcome immunosuppressive environmental triggers, mediating balanced antitumor immunity without causing unwanted inflammation or autoimmunity. To address these hurdles, chimeric receptors with distinct signaling properties are being engineered to function as allies of tumor antigen-specific receptors, modulating unique aspects of T cell function without directly binding to antigen themselves. In this review, we focus on the design and function of these chimeric non-antigen receptors, which fall into three broad categories: 'inhibitory-to-stimulatory' switch receptors that bind natural ligands, enhanced stimulatory receptors that interact with natural ligands, and synthetic receptor-ligand pairs. Our intent is to offer detailed descriptions that will help readers to understand the structure and function of these receptors, as well as inspire development of additional novel synthetic receptors to improve T cell-based cancer therapy.
24899 Ixekizumab sustains high efficacy and a favorable safety profile in burdensome areas in patients with moderate-to-severe psoriasis: 5-year results from UNCOVER-2
Authors: Kim Papp, Andrew Blauvelt, Luis Puig, Hany Elmaraghy, Kyoungah See, Missy McKean-Matthews, Heidi Crane, Alyssa Garrelts, Craig Leonardi
Journal: Journal of the American Academy of Dermatology (2021)
Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn’s disease
Authors: Ling-jie Huang, Xin-tao Mao, Yi-yuan Li, Dan-dan Liu, Ke-qi Fan, Rong-bei Liu, Ting-ting Wu, Hao-li Wang, Yu Zhang, Bing Yang, Cun-qi Ye, Jiang-yan Zhong, Ren-jie Chai, Qian Cao, Jin Jin
Journal: Immunity (2021)
Canadian Regulatory and Health Technology Assessment for Malignant Hematology and Oncology Indications Compared With the US Food and Drug Administration Accelerated Approval Program
Authors: Cheryl Ho, Howard J. Lim, Dean A. Regier
Journal: JAMA Network Open (2021)

This quality improvement study compares US Food and Drug Administration accelerated approvals with Canadian health and technology assessment approvals and timelines for malignant hematology and oncology treatments.
Mutations in the transcription factor FOXO1 mimic positive selection signals to promote germinal center B cell expansion and lymphomagenesis
Authors: Mark P. Roberto, Gabriele Varano, Rosa Vinas-Castells, Antony B. Holmes, Rahul Kumar, Laura Pasqualucci, Pedro Farinha, David W. Scott, David Dominguez-Sola
Journal: Immunity (2021)
GP efforts to cut antibiotic use failed to curb spread of drug resistant E coli, evaluation finds
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Researchers have called for a more radical, multisectoral approach to halting the rise in drug resistant Escherichia coli infections in England after finding that incentivising general practices to reduce antibiotic prescribing on its own was insufficient.

The team from Imperial College London assessed the effects on antimicrobial resistance of NHS England’s “quality premium” scheme, which was introduced in 2015 to reward groups of GPs for reducing inappropriate antibiotic prescribing in primary care, where 70% of antibiotics in England are prescribed.

Their findings, published in the Lancet Infectious Diseases ,1 show that while the intervention did reduce antibiotic prescribing, …
Astrocytic YAP protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model through TGF-β signaling
Authors: Qian Wu, Xuemeng Miao, Jingjing Zhang, Ludan Xiang, Xiuchun Li, Xiaomei Bao, Siyu Du, Mianxian Wang, Shuangda Miao, Yiren Fan, Wei Wang, Xingxing Xu, Xiya Shen, Danlu Yang, Xiwu Wang, Yuanyuan Fang, Lixin Hu, Xuyi Pan, Haoru Dong, Hui Wang, Ying Wang, Jia Li, Zhihui Huang
Journal: Theranostics (2021)

Rationale: Optic neuritis is one of main symptoms in multiple sclerosis (MS) that causes visual disability. Astrocytes are pivotal regulators of neuroinflammation in MS, and astrocytic yes-associated protein (YAP) plays a critical role in neuroinflammation. Meanwhile, YAP signaling is involved in visual impairment, including glaucoma, retinal choroidal atrophy and retinal detachment. However, the roles and underlying mechanisms of astrocytic YAP in neuroinflammation and demyelination of MS-related optic neuritis (MS-ON) remains unclear. Methods: To assess the functions of YAP in MS-ON, experimental autoimmune encephalomyelitis (EAE, a common model of MS) was established, and mice that conditional knockout (CKO) of YAP in astrocytes, YAPGFAP-CKO mice, were successfully generated. Behavior tests, immunostaining, Nissl staining, Hematoxylin-Eosin (HE) staining, TUNEL staining, Luxol Fast Blue (LFB) staining, electron microscopy (EM), quantitative real-time PCR (qPCR), gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) by RNA sequencing were used to examine the function and mechanism of YAP signaling based on these YAPGFAP-CKO mice and EAE model mice. To further explore the potential treatment of YAP signaling in EAE, EAE mice were treated with various drugs, including SRI-011381 that is an agonist of transforming growth factor-β (TGF-β) pathway, and XMU-MP-1 which inhibits Hippo kinase MST1/2 to activate YAP. Results: We found that YAP was significantly upregulated and activated in the astrocytes of optic nerve in EAE mice. Conditional knockout of YAP in astrocytes caused more severe inflammatory infiltration and demyelination in optic nerve, and damage of retinal ganglion cells (RGCs) in EAE mice. Moreover, YAP deletion in astrocytes promoted the activation of astrocytes and microglia, but inhibited the proliferation of astrocytes of optic nerve in EAE mice. Mechanically, TGF-β signaling pathway was significantly down-regulated after YAP deletion in astrocytes. Additionally, both qPCR and immunofluorescence assays confirmed the reduction of TGF-β signaling pathway in YAPGFAP-CKO EAE mice. Interestingly, SRI-011381 partially rescued the deficits in optic nerve and retina of YAPGFAP-CKO EAE mice. Finally, activation of YAP signaling by XMU-MP-1 relieved the neuroinflammation and demyelination in optic nerve of EAE mice. Conclusions: These results suggest astrocytic YAP may prevent the neuroinflammatory infiltration and demyelination through upregulation of TGF-β signaling and provide targets for the development of therapeutic strategies tailored for MS-ON.
Development and Assessment of a Model for Predicting Individualized Outcomes in Patients With Oropharyngeal Cancer
Authors: Lauren J. Beesley, Andrew G. Shuman, Michelle L. Mierzwa, Emily L. Bellile, Benjamin S. Rosen, Keith A. Casper, Mohannad Ibrahim, Sarah M. Dermody, Gregory T. Wolf, Steven B. Chinn, Matthew E. Spector, Robert J. Baatenburg de Jong, Emilie A. C. Dronkers, Jeremy M. G. Taylor
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Recent insights into the biologic characteristics and treatment of oropharyngeal cancer may help inform improvements in prognostic modeling. A bayesian multistate model incorporates sophisticated statistical techniques to provide individualized predictions of survival and recurrence outcomes for patients with newly diagnosed oropharyngeal cancer. <h3>Objective</h3> To develop a model for individualized survival, locoregional recurrence, and distant metastasis prognostication for patients with newly diagnosed oropharyngeal cancer, incorporating clinical, oncologic, and imaging data. <h3>Design, Setting, and Participants</h3> In this prognostic study, a data set was used comprising 840 patients with newly diagnosed oropharyngeal cancer treated at a National Cancer Institute–designated center between January 2003 and August 2016; analysis was performed between January 2019 and June 2020. Using these data, a bayesian multistate model was developed that can be used to obtain individualized predictions. The prognostic performance of the model was validated using data from 447 patients treated for oropharyngeal cancer at Erasmus Medical Center in the Netherlands. <h3>Exposures</h3> Clinical/oncologic factors and imaging biomarkers collected at or before initiation of first-line therapy. <h3>Main Outcomes and Measures</h3> Overall survival, locoregional recurrence, and distant metastasis after first-line cancer treatment. <h3>Results</h3> Of the 840 patients included in the National Cancer Institute–designated center, 715 (85.1%) were men and 268 (31.9%) were current smokers. The Erasmus Medical Center cohort comprised 300 (67.1%) men, with 350 (78.3%) current smokers. Model predictions for 5-year overall survival demonstrated good discrimination, with area under the curve values of 0.81 for the model with and 0.78 for the model without imaging variables. Application of the model without imaging data in the independent Dutch validation cohort resulted in an area under the curve of 0.75. This model possesses good calibration and stratifies patients well in terms of likely outcomes among many competing events. <h3>Conclusions and Relevance</h3> In this prognostic study, a multistate model of oropharyngeal cancer incorporating imaging biomarkers appeared to estimate and discriminate locoregional recurrence from distant metastases. Providing personalized predictions of multiple outcomes increases the information available for patients and clinicians. The web-based application designed in this study may serve as a useful tool for generating predictions and visualizing likely outcomes for a specific patient.
Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials
Authors: Rosie Bradley, Jeremy Braybrooke, Richard Gray, Robert Hills, Zulian Liu, Richard Peto, Lucy Davies, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, Stewart Anderson, Richard Gelber, Luca Gianni, William Jacot, Heikki Joensuu, Alvaro Moreno-Aspitia, Martine Piccart, Michael Press, Edward Romond, Dennis Slamon, Vera Suman, Richard Berry, Clare Boddington, Mike Clarke, Christina Davies, Fran Duane, Vaughan Evans, Jo Gay, Lucy Gettins, Jon Godwin, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Ewan Straiton, Yaochen Wang, John Crown, Evandro de Azambuja, Suzette Delaloge, Helena Fung, Charles Geyer, Marc Spielmann, Pinuccia Valagussa, Kathy Albain, Stewart Anderson, Rodrigo Arriagada, John Bartlett, Elizabeth Bergsten-Nordström, Judith Bliss, Etienne Brain, Lisa Carey, Robert Coleman, Jack Cuzick, Nancy Davidson, Lucia Del Mastro, Angelo Di Leo, James Dignam, Mitch Dowsett, Bent Ejlertsen, Prue Francis, Michael Gnant, Matthew Goetz, Pam Goodwin, Pat Halpin-Murphy, Dan Hayes, Catherine Hill, Reshma Jagsi, Wolfgang Janni, Sibylle Loibl, Eleftherios P Mamounas, Miguel Martín, Hirofumi Mukai, Valentina Nekljudova, Larry Norton, Yasuo Ohashi, Lori Pierce, Philip Poortmans, Vinod Raina, Daniel Rea, Meredith Regan, John Robertson, Emiel Rutgers, Tanja Spanic, Joseph Sparano, Guenther Steger, Gong Tang, Masakazu Toi, Andrew Tutt, Giuseppe Viale, Xiang Wang, Tim Whelan, Nicholas Wilcken, Norman Wolmark, David Cameron, Jonas Bergh, Kathleen I Pritchard, Sandra M Swain
Journal: The Lancet Oncology (2021)

Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality.
Addressing the Global Crisis of Child and Adolescent Mental Health
Authors: Tami D. Benton, Rhonda C. Boyd, Wanjikũ F.M. Njoroge
Journal: JAMA Pediatrics (2021)

Nicole Racine, PhD, RPsych; Brae Anne McArthur, PhD, RPsych; Jessica E. Cooke, MSc; Rachel Eirich, BA; Jenney Zhu, BA; Sheri Madigan, PhD, RPsych
Editor's Note: Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer
Authors: Ju-Won Roh, Jie Huang, Wei Hu, XiaoYun Yang, Nicholas B. Jennings, Vasudha Sehgal, Bo Hwa Sohn, Hee Dong Han, Sun Joo Lee, Duangmani Thanapprapasr, Justin Bottsford-Miller, Behrouz Zand, Heather J. Dalton, Rebecca A. Previs, Ashley N. Davis, Koji Matsuo, Ju-Seog Lee, Prahlad Ram, Robert L. Coleman, Anil K. Sood
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]). Four sets of identical representative images exist: Fig. 4B Hec-1A/Control and Fig. 4B Hec-1A SD+PDGF-AA+HmIgG; Fig. 5B CD31/3G3 and Supplementary Fig. S2 CD31/Paclitaxel; Fig. 5B TUNEL/PBS and
Abstract 8826: Association of TIMI-3 Epicardial Blood Flow Before and After Percutaneous Coronary Intervention with Microvascular Obstruction in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Atsushi Yamamuro, Shuichiro Kaji, Makoto Kinoshita, Natsuhiko Ehara, Takeshi Kitai, Kitae Kim, Atsushi Kobori, Tomoko Tani, Shigefumi Morioka, Toru Kita, Yutaka Furukawa
Journal: Circulation (2011)

Background: The beneficial effects of full restoration of the epicardial coronary flow (TIMI flow grade 3) and spontaneous reperfusion before percutaneous coronary intervention (PCI) are well known. However, previous studies evaluating the influence of pre-PCI and post-PCI TIMI flow grade on cardiac mortality reported conflicting results. The impact of epicardial flow before and after PCI on microvascular damage in patients with ST-segment elevation myocardial infarction (STEMI) has been insufficiently studied. The purpose of this study was to examine the interaction of TIMI-3 antegrade flow before and after PCI on degree of microvascular damage in patients with STEMI. Methods: Two hundred and eleven consecutive patients with first anterior STEMI who underwent successful PCI (post-TIMI 2,3 flow) were subjected to coronary flow measurement with a Doppler guidewire. The coronary flow velocity spectrum provided the following parameters: systolic peak velocity (SPV) and diastolic deceleration time (DDT). We defined the presence of microvascular obstruction as DDT of ≤ 600 ms and the presence of systolic flow reversal. We classified the patients into three categories according to the post-TIMI 2 flow (group 1), the pre-TIMI 0-2 and post-TIMI 3 flow (group 2), the pre- and post-TIMI 3 flow (group 3). Results: As for the relationship between the epicardial blood flow before and after PCI and the severity of microvascular damage, group 1 was at the highest risk of microvascular obstruction, while group 3 was at the lowest: 32/40 (80%) for group 1, 55/142 (39%) for group 2, and 0/29 (0%) for group 3 (p&lt;0.05). The DDT were shortest in group 1 and longest in group 3 (358±226 vs. 596±227 vs. 784±133 ms; p&lt;0.05) and the SPV were lowest in group 1 and highest in group 3 (-23±22 vs. -1±24 vs. 14±16 cm/s; p&lt;0.05). Conclusions: In patients with STEMI, epicardial blood flow both before and after PCI may have significant impacts on ischemic microvascular damage. In particular, all patients who achieved reperfusion with TIMI-3 epicardial blood flow before and after PCI were successfully salvaged from microvascular obstruction. Of critical importance, the effect of pre-procedural TIMI-3 flow on microvascular integrity persisted even when corrected for post-procedural TIMI-3 flow.