tbuckley/cabot-search huggingface dataset:
The Effect of BMI and Type 2 Diabetes on Socioeconomic Status: A Two-Sample Multivariable Mendelian Randomization Study
Authors: Sara Pedron, Christoph F. Kurz, Lars Schwettmann, Michael Laxy
Journal: Diabetes Care (2021)

OBJECTIVE To assess the independent causal effect of BMI and type 2 diabetes (T2D) on socioeconomic outcomes by applying two-sample Mendelian randomization (MR) analysis. RESEARCH DESIGN AND METHODS We performed univariable and multivariable two-sample MR to jointly assess the effect of BMI and T2D on socioeconomic outcomes. We used overlapping genome-wide significant single nucleotide polymorphisms for BMI and T2D as instrumental variables. Their causal impact on household income and regional deprivation was assessed using summary-level data from the UK Biobank. RESULTS In the univariable analysis, higher BMI was related to lower income (marginal effect of 1-SD increase in BMI [β = −0.092; 95% CI −0.138; −0.047]) and higher deprivation (β = 0.051; 95% CI 0.022; 0.079). In the multivariable MR, the effect of BMI controlling for diabetes was slightly lower for income and deprivation. Diabetes was not associated with these outcomes. CONCLUSIONS High BMI, but not diabetes, shows a causal link with socioeconomic outcomes.
In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug
Authors: Changzhi Shi, Jelisaveta Ignjatović, Tingting Liu, Meihua Han, Dongmei Cun, Jelena Đuriš, Mingshi Yang, Sandra Cvijić
Journal: Asian Journal of Pharmaceutical Sciences (2021)

This study aims to understand the absorption patterns of three different kinds of inhaled formulations via in silico modeling using budesonide (BUD) as a model drug. The formulations investigated in this study are: (i) commercially available micronized BUD mixed with lactose (BUD-PT), (ii) BUD nanocrystal suspension (BUD-NC), (iii) BUD nanocrystals embedded hyaluronic acid microparticles (BUD-NEM). The deposition patterns of the three inhaled formulations in the rats' lungs were determined in vivo and in silico predicted, which were used as inputs in GastroPlus™ software to predict drug absorption following aerosolization of the tested formulations. BUD pharmacokinetics, estimated based on intravenous data in rats, was used to establish a drug-specific in silico absorption model. The BUD-specific in silico model revealed that drug pulmonary solubility and absorption rate constant were the key factors affecting pulmonary absorption of BUD-NC and BUD-NEM, respectively. In the case of BUD-PT, the in silico model revealed significant gastrointestinal absorption of BUD, which could be overlooked by traditional in vivo experimental observation. This study demonstrated that in vitro-in vivo-in silico approach was able to identify the key factors that influence the absorption of different inhaled formulations, which may facilitate the development of orally inhaled formulations with different drug release/absorption rates.
CRISPR-Cas9: A method for establishing rat models of drug metabolism and pharmacokinetics
Authors: Jian Lu, Jie Liu, Yuanqing Guo, Yuanjin Zhang, Yeye Xu, Xin Wang
Journal: Acta Pharmaceutica Sinica B (2021)

The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as Cyp, Abcb1, Oatp1b2 gene knockout rats. These new rat models are not only widely used in the study of drug metabolism, chemical toxicity, and carcinogenicity, but also promote the study of DMPK related mechanism, and further strengthen the relationship between drug metabolism and pharmacology/toxicology. This review systematically introduces the advantages and disadvantages of CRISPR-Cas9, summarizes the methods of establishing DMPK rat models, discusses the main challenges in this field, and proposes strategies to overcome these problems.
Targeting hypoxic tumor microenvironment in pancreatic cancer
Authors: Jinxin Tao, Gang Yang, Wenchuan Zhou, Jiangdong Qiu, Guangyu Chen, Wenhao Luo, Fangyu Zhao, Lei You, Lianfang Zheng, Taiping Zhang, Yupei Zhao
Journal: Journal of Hematology & Oncology (2021)

Abstract Attributable to its late diagnosis, early metastasis, and poor prognosis, pancreatic cancer remains one of the most lethal diseases worldwide. Unlike other solid tumors, pancreatic cancer harbors ample stromal cells and abundant extracellular matrix but lacks vascularization, resulting in persistent and severe hypoxia within the tumor. Hypoxic microenvironment has extensive effects on biological behaviors or malignant phenotypes of pancreatic cancer, including metabolic reprogramming, cancer stemness, invasion and metastasis, and pathological angiogenesis, which synergistically contribute to development and therapeutic resistance of pancreatic cancer. Through various mechanisms including but not confined to maintenance of redox homeostasis, activation of autophagy, epigenetic regulation, and those induced by hypoxia-inducible factors, intratumoral hypoxia drives the above biological processes in pancreatic cancer. Recognizing the pivotal roles of hypoxia in pancreatic cancer progression and therapies, hypoxia-based antitumoral strategies have been continuously developed over the recent years, some of which have been applied in clinical trials to evaluate their efficacy and safety in combinatory therapies for patients with pancreatic cancer. In this review, we discuss the molecular mechanisms underlying hypoxia-induced aggressive and therapeutically resistant phenotypes in both pancreatic cancerous and stromal cells. Additionally, we focus more on innovative therapies targeting the tumor hypoxic microenvironment itself, which hold great potential to overcome the resistance to chemotherapy and radiotherapy and to enhance antitumor efficacy and reduce toxicity to normal tissues.
Inconsistent platelet-rich plasma product from devices cleared by the US FDA: A retrospective review of clinic data
Authors: Meyeneobong Inyang, Javed A. Shaik, Noora Hussain, Maria Hordinsky, Neil Sadick, Graham Gregorich, Jessica Asiala, Rebecca Freese, Ronda S. Farah
Journal: Journal of the American Academy of Dermatology (2021)
Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury
Authors: Ellen E. Gillis, Michael W. Brands, Jennifer C. Sullivan
Journal: Journal of the American Society of Nephrology (2021)

Background Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. Methods To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. Results After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. Conclusions In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.
Brown adipose tissue is associated with cardiometabolic health
Authors: Tobias Becher, Srikanth Palanisamy, Daniel J. Kramer, Mahmoud Eljalby, Sarah J. Marx, Andreas G. Wibmer, Scott D. Butler, Caroline S. Jiang, Roger Vaughan, Heiko Schöder, Allyn Mark, Paul Cohen
Journal: Nature Medicine (2021)
CT Angiography Followed by Invasive Angiography in Patients With Moderate or Severe Ischemia-Insights From the ISCHEMIA Trial
Authors: G B John Mancini, Jonathan Leipsic, Matthew J Budoff, Cameron J Hague, James K Min, Susanna R Stevens, Harmony R Reynolds, Sean M O'Brien, Leslee J Shaw, Cholenahally N Manjunath, Kreton Mavromatis, Marcin Demkow, Jose Luis Lopez-Sendon, Alexander M Chernavskiy, Gilbert Gosselin, Herwig Schuchlenz, Gerard P Devlin, Anoop Chauhan, Sripal Bangalore, Judith S Hochman, David J Maron
Journal: JACC. Cardiovascular imaging (2021)
<i>BRCA2</i>, <i>ATM</i>, and <i>CDK12</i> Defects Differentially Shape Prostate Tumor Driver Genomics and Clinical Aggression
Authors: Evan Warner, Cameron Herberts, Simon Fu, Steven Yip, Amanda Wong, Gang Wang, Elie Ritch, Andrew J. Murtha, Gillian Vandekerkhove, Nicolette M. Fonseca, Arkhjamil Angeles, Arshia Beigi, Elena Schönlau, Kevin Beja, Matti Annala, Daniel Khalaf, Kim N. Chi, Alexander W. Wyatt
Journal: Clinical Cancer Research (2021)

Abstract Purpose: DNA damage repair (DDR) defects are common across cancer types and can indicate therapeutic vulnerability. Optimal exploitation of DDR defects in prostate cancer requires new diagnostic strategies and a better understanding of associated clinical genomic features. Experimental Design: We performed targeted sequencing of 1,615 plasma cell-free DNA samples from 879 patients with metastatic prostate cancer. Depth-based copy-number calls and heterozygous SNP imbalance were leveraged to expose DDR-mutant allelic configuration and categorize mechanisms of biallelic loss. We used split-read structural variation analysis to characterize tumor suppressor rearrangements. Patient-matched archival primary tissue was analyzed identically. Results: BRCA2, ATM, and CDK12 were the most frequently disrupted DDR genes in circulating tumor DNA (ctDNA), collectively mutated in 15% of evaluable cases. Biallelic gene disruption via second somatic alteration or mutant allele–specific imbalance was identified in 79% of patients. A further 2% exhibited homozygous BRCA2 deletions. Tumor suppressors TP53, RB1, and PTEN were controlled via disruptive chromosomal rearrangements in BRCA2-defective samples, but via oncogene amplification in context of CDK12 defects. TP53 mutations were rare in cases with ATM defects. DDR mutations were re-detected across 94% of serial ctDNA samples and in all available archival primary tissues, indicating they arose prior to metastatic progression. Loss of BRCA2 and CDK12, but not ATM, was associated with poor clinical outcomes. Conclusions: BRCA2, ATM, and CDK12 defects are each linked to distinct prostate cancer driver genomics and aggression. The consistency of DDR status in longitudinal samples and resolution of allelic status underscores the potential for ctDNA as a diagnostic tool.
Abstract 20097: Long-term Effect of Non-paroxysmal Atrial Fibrillation Ablation is Not Reflected by the Prolongation of Atrial Fibrillation Cycle Length but by the Regional Organization of Wave Dynamics Detected by Novel Online Realtime Phase Mapping System Just After the Ablation
Authors: Kensuke Sakata, Tomoya Ozawa, Yusuke Okuyama, Ryo Haraguchi, Takeshi Tsuchiya, Minoru Horie, Takashi Ashihara
Journal: Circulation (2017)

Introduction: Modulation of atrial fibrillation (AF) drivers has been proposed as one of the effective ablation strategies for non-paroxysmal AF (Non-PAF). The efficacy of AF modulation is usually ...
AB0585 SINGLE CENTER EXPERIENCE OF CLINICAL PROFILE OF INFLAMMATORY MYOSITIS FROM INDIA
Authors: N. Kulkarni, A. Venugopalan, M. Saluja, A. Chopra
Journal: Annals of the Rheumatic Diseases (2020)

Background: Clinical profile of myositis differs in respect of the setting. We present a single center experience from a community based referral center Objectives: STUDY CLINICAL PROFILE OF INFLAMMATORY MYOSITIS (IM) Methods: We present data from 114 patients of connective tissue disorders (CTD) with dominant Inflammatory Myopathy(IM) evaluated in CRD where we have patient database since 1996. Standard investigations &amp; ELISA, immunoblot and nephlometry to assay autoantibodies (AAb) were done. Data extraction done from 2005-2017 Results: 36 and 28 patients respectively diagnosed as dominant idiopathic dematomyositis (DM) and polymyositis (PM); remaining 41 patients showed overlap (OCTD). Mean onset age range 33-40 years in each subset with women dominance. Exclusive proximal muscle involvement seen 64% DM, 67% PM and 43% OCTD. 12 of OCTD showed classical DM rash. Raynauds’s phenomenon was seen in 38% (25% DM, 10% PM, 65% OCTD). 83% OCTD showed inflammatory polyarthritis; DM 29% and PM 42%. Two patients DM also diagnosed malignancy (ovarian CA). 25% DM, nil PM and 31.7% OCTD showed CT based lung findings. Mean creatinine phosphokinase at diagnosis were DM 1580, PM 2239 &amp; OCTD 830. EMG required in 48 patients confirmed diagnosis (DM 17, PM 16 and OCTD 15). Seven patients with diagnostic dilemma/ poor therapy response required muscle histopathology confirmation. 59% DM,69% PM and 84% OCTD were seropositive ANA positive in 71%(ENA profile available for most). All Patients received steroids. Methotrexate prescribed in (92%), Azthioprine in (28%), hydroxychloroquine in (88%) with majority showing good response. Mycophenolate prescribed in (6%) for aggressive disease, IVIG in 2 patients for acute IIM with interstitial pneumonitis. Rituximab was prescribed in 4 resistant cases; all responding favourably. Mortality data of 4 patients(severe myositis(1), interstitial pneumonitis(1), ovarian cancer(1), septic shock(1)) was available. Antesynthatase syndrome noted in 9 patients. Conclusion: Overlap CTD with myositis seems more common profile than DM or PM. Response to therapy was satisfactory with steroids and methotrexate being the mainstay. Rituximab is a promising biological agent in chronic resistant cases. References: [1]A Kumar. Idiopathic Inflammatory Myopathies. Suppliment to JAPI, JUNE 2006, VOL. 54; Pg 62-66 [2]R Porkodi et al Clinical Spectrum of Inflammatory Myositis in South India - A Ten Year Study. J Assoc Physicians India 2002;50:1255-1258 [3]Chowdhary V, Aggarwal A, Misra R. Prevalence and clinical association of myositis-specific autoantibodies in North Indian patients with idiopathic inflammatory myopathy. APLAR J Rheumatol 2 001. Acknowledgments : STAFF AND PATIENTS OF CENTER FOR RHEUMATIC DISEASES, PUNE Disclosure of Interests: : NACHIKET KULKARNI Speakers bureau: PFIZER, NOVARTIS, YANSEN, Anuradha Venugopalan: None declared, MANJIT SALUJA: None declared, Arvind Chopra Grant/research support from: Zydus Pharamceutical Ltd India
Different Gene Networks are Disturbed by Zika Virus Infection in a Mouse Microcephaly Model
Authors: Yafei Chang, Yisheng Jiang, Cui Li, Qin Wang, Feng Zhang, Cheng-Feng Qin, Qing-Feng Wu, Jing Li, Zhiheng Xu
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract The association of Zika virus (ZIKV) infection with microcephaly has raised alarm worldwide. Their causal link has been confirmed in different animal models infected by ZIKV. However, the molecular mechanisms underlying ZIKV pathogenesis are far from clear. Hence, we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biological and molecular networks underpinning microcephaly. We found significant dysregulation of the sub-networks associated with brain development, immune response, cell death, microglial cell activation, and autophagy amongst others. We provided detailed analysis of the related complicated gene networks and the links between them. Additionally, we analyzed the signaling pathways that were likely to be involved. This report provides systemic insights into not only the pathogenesis, but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.
Surgical planning of pelvic tumor using multi-view CNN with relation-context representation learning
Authors: Yang Qu, Xiaomin Li, Zhennan Yan, Liang Zhao, Lichi Zhang, Chang Liu, Shuaining Xie, Kang Li, Dimitris Metaxas, Wen Wu, Yongqiang Hao, Kerong Dai, Shaoting Zhang, Xiaofeng Tao, Songtao Ai
Journal: Medical Image Analysis (2021)

Limb salvage surgery of malignant pelvic tumors is the most challenging procedure in musculoskeletal oncology due to the complex anatomy of the pelvic bones and soft tissues. It is crucial to accurately resect the pelvic tumors with appropriate margins in this procedure. However, there is still a lack of efficient and repetitive image planning methods for tumor identification and segmentation in many hospitals. In this paper, we present a novel deep learning-based method to accurately segment pelvic bone tumors in MRI. Our method uses a multi-view fusion network to extract pseudo-3D information from two scans in different directions and improves the feature representation by learning a relational context. In this way, it can fully utilize spatial information in thick MRI scans and reduce over-fitting when learning from a small dataset. Our proposed method was evaluated on two independent datasets collected from 90 and 15 patients, respectively. The segmentation accuracy of our method was superior to several comparing methods and comparable to the expert annotation, while the average time consumed decreased about 100 times from 1820.3 seconds to 19.2 seconds. In addition, we incorporate our method into an efficient workflow to improve the surgical planning process. Our workflow took only 15 minutes to complete surgical planning in a phantom study, which is a dramatic acceleration compared with the 2-day time span in a traditional workflow.
Sonia Rohini Hall
Authors: Emma Kendon
Journal: BMJ (2021)

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Intrapartum Maternal Oxygen Supplementation—Friend or Foe?
Authors: Mohan Pammi, Steven L. Clark, Alireza A. Shamshirsaz
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Cutaneous Clopidogrel Hypersensitivity: Give Steroids and Do Not Stop the Clopidogrel⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Paul A. Gurbel, Young-Hoon Jeong, Udaya S. Tantry
Journal: Journal of the American College of Cardiology (2011)
Genome-wide study of salivary miRNAs identifies miR-423-5p as promising diagnostic and prognostic biomarker in oral squamous cell carcinoma
Authors: Chiara Romani, Elisa Salviato, Alberto Paderno, Laura Zanotti, Antonella Ravaggi, Alberto Deganello, Giulia Berretti, Tommaso Gualtieri, Sergio Marchini, Maurizio D'Incalci, Davide Mattavelli, Cesare Piazza, Paolo Bossi, Chiara Romualdi, Piero Nicolai, Eliana Bignotti
Journal: Theranostics (2021)

Survival rates of oral squamous cell carcinoma (OSCC) remained substantially unchanged over the last decades; thus, additional prognostic tools are strongly needed.Salivary miRNAs have emerged as excellent non-invasive cancer biomarker candidates, but their association with OSCC prognosis has not been investigated yet.In this study, we analyzed global salivary miRNA expression in OSCC patients and healthy controls, with the aim to define its diagnostic and prognostic potential.Methods: Saliva was collected from patients with newly diagnosed untreated primary OSCC and healthy controls.Global profiling of salivary miRNAs was carried out through a microarray approach, while signature validation was performed by quantitative real-time PCR (RT-qPCR).A stringent statistical approach for microarray and RT-qPCR data normalization was applied.The diagnostic performance of miRNAs and their correlation with OSCC prognosis were comprehensively analyzed.Results: In total, 25 miRNAs emerged as differentially expressed between OSCC patients and healthy controls and, among them, seven were significantly associated with disease-free survival (DFS).miR-106b-5p, miR-423-5p and miR-193b-3p were expressed at high levels in saliva of OSCC patients and their combination displays the best diagnostic performance (ROC -AUC = 0.98).Moreover, high expression of miR-423-5p was an independent predictor of poor DFS, when included in multivariate survival analysis with the number of positive lymph nodes -the only significant clinical prognosticator.Finally, we observed a significant decrease in miR-423-5p expression in matched post-operative saliva samples, suggesting its potential cancer-specific origin.Conclusion: Salivary miRNAs identified in our cohort of patients show to be accurate in OSCC detection and to effectively stratify patients according to their likelihood of relapse.These results, if IvyspringInternational Publisher validated in an independent set of patients, could be particularly promising for screening/follow-up of high-risk populations and useful for preoperative prognostic assessment.