tbuckley/cabot-search huggingface dataset:
Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival
Authors: Chen Hao Lo, Gemma Shay, Jeremy J. McGuire, Tao Li, Kenneth H. Shain, Jun Yong Choi, Rita Fuerst, William R. Roush, Anna M. Knapinska, Gregg B. Fields, Conor C. Lynch
Journal: Cancer Research (2021)

Abstract Multiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type I collagen–rich bone matrix by activated osteoclasts results in the release of sequestered growth factors that can drive progression of the disease. Matrix metalloproteinase-13 (MMP13) is a collagenase expressed predominantly in the skeleton by mesenchymal stromal cells (MSC) and MSC-derived osteoblasts. Histochemical analysis of human multiple myeloma specimens also demonstrated that MMP13 largely localizes to the stromal compartment compared with CD138+ myeloma cells. In this study, we further identified that multiple myeloma induces MMP13 expression in bone stromal cells. Because of its ability to degrade type I collagen, we examined whether bone stromal–derived MMP13 contributed to myeloma progression. Multiple myeloma cells were inoculated into wild-type or MMP13–null mice. In independent in vivo studies, MMP13–null mice demonstrated significantly higher overall survival rates and lower levels of bone destruction compared with wild-type controls. Unexpectedly, no differences in type I collagen processing between the groups were observed. Ex vivo stromal coculture assays showed reduced formation and activity in MMP13–null osteoclasts. Analysis of soluble factors from wild-type and MMP13–null MSCs revealed decreased bioavailability of various osteoclastogenic factors including CXCL7. CXCL7 was identified as a novel MMP13 substrate and regulator of osteoclastogenesis. Underscoring the importance of host MMP13 catalytic activity in multiple myeloma progression, we demonstrate the in vivo efficacy of a novel and highly selective MMP13 inhibitor that provides a translational opportunity for the treatment of this incurable disease. Significance: Genetic and pharmacologic approaches show that bone stromal–derived MMP13 catalytic activity is critical for osteoclastogenesis, bone destruction, and disease progression.
Extrathoracic muscle wasting in exacerbations of COPD: no longer outside the region of interest
Authors: Neil J Greening, Michael I Polkey, Hamish Joseph Cameron McAuley
Journal: Thorax (2021)

While airflow limitation is used to diagnose chronic obstructive pulmonary disease (COPD), it is well established that forced expiratory volume in one second alone relates poorly to mortality1 or health-related quality of life.2 Skeletal muscle dysfunction has been shown to be a better predictor than lung function for both prognosis3 and risk of hospitalisation.4 Moreover, skeletal muscle weakness is increasingly recognised as an important component of both frailty and sarcopaenia. Acute exacerbations of COPD (AECOPD) are a feature of many patients with COPD, with intermittent worsening of symptoms contrasting to many other chronic conditions. The impact of exacerbations is well established, with prevention and treatment an important goal for therapy with COPD.

Therefore, the interaction between exacerbations and skeletal muscle dysfunction is of great interest. A reduction in both exercise capacity and quadriceps strength has been reported in patients admitted with acute exacerbation of COPD5 and to a lesser extent among patients treated as an outpatient6 but the longer-term impact on muscle mass is unknown. Similarly, how therapies such as pulmonary rehabilitation (PR) may impact on future exacerbations risk in the longer term is less clear, although the short-term benefits of this therapy after AECOPD are established.7

In this issue of Thorax , Mason et al 8 report an association between exacerbation frequency and accelerated muscle loss in patients with COPD. Using …
Food poverty should not be allowed to continue—government action is needed
Authors: Michael Craig Watson, John Lloyd
Journal: BMJ (2021)

The BMJ Appeal has the potential to substantially and immediately improve food insecurity and children’s health.1 Early last year the Royal College of Paediatrics and Child Health’s report, State of Child Health 2020 , painted a bleak picture of child health in the UK,23 and since then the covid-19 pandemic has intensified many difficulties that families face.4

Healthy eating …
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries
Authors: Hyuna Sung, Jacques Ferlay, Rebecca L. Siegel, Mathieu Laversanne, Isabelle Soerjomataram, Ahmedin Jemal, Freddie Bray
Journal: CA A Cancer Journal for Clinicians (2021)

Abstract This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2‐fold to 3‐fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied &lt;2‐fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
Interpreting the Findings of a Meta-analysis of Psychosocial Interventions in Bipolar Disorder
Authors: David J. Miklowitz, Toshi A. Furukawa, Andrea Cipriani
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Erratum to: “MLKL-dependent signaling regulates autophagic flux in a murine model of non-alcoholic-associated fatty liver and steatohepatitis (J Hepatol 2020; 73: 616–627)”
Authors: Xiaoqin Wu, Kyle L. Poulsen, Carlos Sanz-Garcia, Emily Huang, Megan R. McMullen, Sanjoy Roychowdhury, Srinivasan Dasarathy, Laura E. Nagy
Journal: Journal of Hepatology (2021)
Major Update: Remdesivir for Adults With COVID-19
Authors: Anjum S. Kaka, Roderick MacDonald, Nancy Greer, Kathryn Vela, Wei Duan-Porter, Adam Obley, Timothy J. Wilt
Journal: Annals of Internal Medicine (2021)

Remdesivir is being studied and used for treatment of coronavirus disease 2019 (COVID-19).To update a previous review of remdesivir for adults with COVID-19, including new meta-analyses of patients with COVID-19 of any severity compared with control.Several sources from 1 January 2020 through 7 December 2020.English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. New evidence is incorporated by using living review methods.1 reviewer abstracted data; a second reviewer verified the data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used.The update includes 5 RCTs, incorporating data from a new large RCT and the final results of a previous RCT. Compared with control, a 10-day course of remdesivir probably results in little to no reduction in mortality (risk ratio [RR], 0.93 [95% CI, 0.82 to 1.06]; 4 RCTs) but may result in a small reduction in the proportion of patients receiving mechanical ventilation (RR, 0.71 [CI, 0.56 to 0.90]; 3 RCTs). Remdesivir probably results in a moderate increase in the percentage of patients who recovered and a moderate decrease in serious adverse events and may result in a large reduction in time to recovery. Effect on hospital length of stay or percentage remaining hospitalized is mixed. Compared with a 10-day course for those not requiring ventilation at baseline, a 5-day course may reduce mortality, the need for ventilation, and serious adverse events while increasing the percentage of patients who recovered or clinically improved.Summarizing findings was challenging because of varying disease severity definitions and outcomes.In hospitalized adults with COVID-19, remdesivir probably results in little to no mortality difference but probably improves the percentage recovered and reduces serious harms and may result in a small reduction in the proportion receiving ventilation. For patients not receiving ventilation, a 5-day course may provide greater benefits and fewer harms with lower drug costs than a 10-day course.U.S. Department of Veterans Affairs.
A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance
Authors: Alexandra D. Dreyfuss, Denisa Goia, Khayrullo Shoniyozov, Swapnil V. Shewale, Anastasia Velalopoulou, Susan Mazzoni, Harris Avgousti, Scott D. Metzler, Paco E. Bravo, Steven J. Feigenberg, Bonnie Ky, Ioannis I. Verginadis, Constantinos Koumenis
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. Experimental Design: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9–11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. Results: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P &amp;lt; 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P &amp;lt; 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose. Conclusions: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.
Prevalence of cat induced allergic rhinitis in children with chronic and frequent rhinitis
Authors: Nichaporn Chalermpalanupap, Watcharoot Kanchongkittiphon, Wiparat Manuyakorn, Woralak Sutiratanachai, Suwat Benjaponpitak, Cherapat Sasisakulporn, Potjanee Kiewngam, Wanlapa Jotikasthira
Journal: Journal of Allergy and Clinical Immunology (2021)
Diagnosis and Treatment of Hip and Knee Osteoarthritis
Authors: Jeffrey N. Katz, Kaetlyn R. Arant, Richard F. Loeser
Journal: JAMA (2021)

<h3>Importance</h3> Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US. Osteoarthritis is the most frequent reason for activity limitation in adults. This Review focuses on hip and knee OA. <h3>Observations</h3> Osteoarthritis can involve almost any joint but typically affects the hands, knees, hips, and feet. It is characterized by pathologic changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of valued activities, such as walking for exercise and dancing. Risk factors include age (33% of individuals older than 75 years have symptomatic and radiographic knee OA), female sex, obesity, genetics, and major joint injury. Persons with OA have more comorbidities and are more sedentary than those without OA. The reduced physical activity leads to a 20% higher age-adjusted mortality. Several physical examination findings are useful diagnostically, including bony enlargement in knee OA and pain elicited with internal hip rotation in hip OA. Radiographic indicators include marginal osteophytes and joint space narrowing. The cornerstones of OA management include exercises, weight loss if appropriate, and education—complemented by topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) in those without contraindications. Intra-articular steroid injections provide short-term pain relief and duloxetine has demonstrated efficacy. Opiates should be avoided. Clinical trials have shown promising results for compounds that arrest structural progression (eg, cathepsin K inhibitors, Wnt inhibitors, anabolic growth factors) or reduce OA pain (eg, nerve growth factor inhibitors). Persons with advanced symptoms and structural damage are candidates for total joint replacement. Racial and ethnic disparities persist in the use and outcomes of joint replacement. <h3>Conclusions and Relevance</h3> Hip and knee OA are highly prevalent and disabling. Education, exercise and weight loss are cornerstones of management, complemented by NSAIDs (for patients who are candidates), corticosteroid injections, and several adjunctive medications. For persons with advanced symptoms and structural damage, total joint replacement effectively relieves pain.
Corrigendum to “Noninvasive imaging evaluation of tumor immune microenvironment to predict outcomes in gastric cancer”
Authors: Y. Jiang, H. Wang, J. Wu, C. Chen, Q. Yuan, W. Huang, T. Li, S. Xi, Y. Hu, Z. Zhou, Y. Xu, G. Li, R. Li
Journal: Annals of Oncology (2021)
TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers
Authors: Nisha B. Nagarsheth, Scott M. Norberg, Andrew L. Sinkoe, Sabina Adhikary, Thomas J. Meyer, Justin B. Lack, Andrew C. Warner, Colleen Schweitzer, Stacey L. Doran, Soumya Korrapati, Sanja Stevanović, Cornelia L. Trimble, Jennifer A. Kanakry, Mohammad Hadi Bagheri, Erin Ferraro, Stephanie H. Astrow, Adrian Bot, William C. Faquin, David Stroncek, Nikolaos Gkitsas, Steven Highfill, Christian S. Hinrichs
Journal: Nature Medicine (2021)
Canagliflozin Reduces All-cause Hospitalization in Patients with Type 2 Diabetes Mellitus
Authors: Kent Y. Feng, Jagadish Gogate, C.V. Damaraju, JingWei Li, Meg J. Jardine, Vlado Perkovic, Jaime D. Blais, Michael Pfeifer, Bruce Neal, Kenneth W. Mahaffey
Journal: Metabolism (2021)
Analyses of δ-catenin gene overexpression in human prostate cancer
Authors: Tao Wang, Yan-Hua Chen, Beverly Jeansonne, Heng Hong, Yan Zeng, Kwonseop Kim, Sonja Bareiss, Qun Lu
Journal: Cancer Research (2007)

1022  δ-Catenin is an armadillo domain-containing p120ctn family protein, and its distribution is restricted to the brain. However, our recent study showed that δ-catenin expression is significantly increased in a number of cancer types outside the brain. These include cancerous tissues of breast, esophagus, ovary, as well as human prostatic adenocarcinomas, although the nature of δ-catenin upregulation in prostate cancer was unclear. In this study, we systematically analyzed the δ-catenin gene (CTNND2) transcription and translation patterns in human prostate cancer cell lines and primary human prostatic adenocarcinomas. δ-Catenin showed consistent upregulation at both transcriptional and translational levels when compared to that of controls. Analyses of δ-catenin CpG islands in the promoter region in benign and prostate cancer specimens revealed no significant differences in methylation status. Real-time PCR analyses found no evidence of gene amplification in δ-catenin. However, we have observed an increased incidence of mutations in the promoter region of δ-catenin gene when compared to that of benign specimens as well as to that of peripheral blood samples of normal control subjects. At the protein level, there was no evidence of mutations in the entire coding region of δ-catenin. These studies support the hypothesis that increased gene transcription activity is an important primary cause of δ-catenin upregulation in human prostate cancer. This study was supported in part by NIH CA111891 and Department of Defense W81XWH-05-1-0028.
Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific <i>XPO1</i> translation in epithelial cells
Authors: Ane Olazagoitia-Garmendia, Linda Zhang, Paula Mera, Julie K Godbout, Maialen Sebastian-DelaCruz, Iraia Garcia-Santisteban, Luis Manuel Mendoza, Alain Huerta, Iñaki Irastorza, Govind Bhagat, Peter H Green, Laura Herrero, Dolors Serra, Jose Antonio Rodriguez, Elena F Verdu, Chuan He, Jose Ramon Bilbao, Ainara Castellanos-Rubio
Journal: Gut (2021)

Objectives Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5’UTR of XPO1 in the inflammatory environment characteristic of the coeliac intestinal epithelium. Design The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (m 6 A)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD. Results Individuals harbouring the risk allele had higher m 6 A methylation in the 5’UTR of XPO1 RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall m 6 A methylation in humans as well as in in vitro and in vivo models. Conclusion We identify a novel m 6 A-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at m 6 A proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.
Evolutions in the Management of Hepatocellular Carcinoma over Last 4 Decades: An Analysis from the 100 Most Influential Articles in the Field
Authors: Gang Xu, Bao Jin, Xiaomeng Xian, Huayu Yang, Haitao Zhao, Shunda Du, Masatoshi Makuuchi, Timothy M. Pawlik, Yilei Mao
Journal: Liver Cancer (2021)

Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment.The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database.The 100 most cited articles were identified with an average of 738 citations (range: 349-6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA (n = 35), followed by Italy (n = 28), mainland China (n = 26), and Japan (n = 24). The surgical management was the most studied topic (n = 33). The Annals of Surgery published the highest number of papers (n = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy.Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.