tbuckley/cabot-search huggingface dataset:
Effect of select berries on estrogen-induced mammary tissue proliferation
Authors: Srivani Ravoori, Manicka Vadhanam, Hina Kausar, Afsoon Moktar, Pavani Vuppalapati, David Schultz, Ramesh Gupta
Journal: Cancer Research (2008)

3821  Epidemiological studies have associated decreased risk of several diseases with increased intake of fruits and vegetables. Our previous studies with black raspberry and blueberry showed significant protection against estrogen-induced mammary carcinogenicity in the ACI rat model. Here we demonstrate that the anticarcinogenicity may be in part due to the inhibition of mammary cell proliferation. Female ACI rats were divided into four groups (n=5 each). Each group received either control diet or diet supplemented with powder of black raspberry and blueberry (5% each, w/w). Two weeks later three groups, one on control diet and other two on berry diets, were treated with 17s-estradiol (9 mg) by subcutaneous silastic implants. Three weeks after estrogen treatment, all groups were euthanized and blood and mammary tissue were collected and snap frozen. A portion of mammary tissue was processed for histopathology. All groups of animals showed similar body-weight gains and had similar diet intake, irrespective of the diet, indicating that the berry diets were well tolerated. Sections were stained for PCNA by immunohistochemistry to measure mammary tissue proliferation. All groups receiving estrogen treatment showed increased mammary cell proliferation based on PCNA staining compared with sham treatment. However, significant differences were observed among groups: the blueberry diet lowered the proliferation index by 66% (p
Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis
Authors: Ana Campos Codo, Gustavo Gastão Davanzo, Lauar de Brito Monteiro, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, João Victor Virgilio-da-Silva, Juliana Silveira Prodonoff, Victor Corasolla Carregari, Carlos Alberto Oliveira de Biagi Junior, Fernanda Crunfli, Jeffersson Leandro Jimenez Restrepo, Pedro Henrique Vendramini, Guilherme Reis-de-Oliveira, Karina Bispo dos Santos, Daniel A. Toledo-Teixeira, Pierina Lorencini Parise, Matheus Cavalheiro Martini, Rafael Elias Marques, Helison R. Carmo, Alexandre Borin, Laís Durço Coimbra, Vinícius O. Boldrini, Natalia S. Brunetti, Andre S. Vieira, Eli Mansour, Raisa G. Ulaf, Ana F. Bernardes, Thyago A. Nunes, Luciana C. Ribeiro, Andre C. Palma, Marcus V. Agrela, Maria Luiza Moretti, Andrei C. Sposito, Fabrício Bíscaro Pereira, Licio Augusto Velloso, Marco Aurélio Ramirez Vinolo, André Damasio, José Luiz Proença-Módena, Robson Francisco Carvalho, Marcelo A. Mori, Daniel Martins-de-Souza, Helder I. Nakaya, Alessandro S. Farias, Pedro M. Moraes-Vieira
Journal: Cell Metabolism (2020)
High SARS-CoV-2 antibody prevalence among healthcare workers exposed to COVID-19 patients
Authors: Yuxin Chen, Xin Tong, Jian Wang, Weijin Huang, Shengxia Yin, Rui Huang, Hailong Yang, Yong Chen, Aijun Huang, Yong Liu, Yan Chen, Ling Yuan, Xiaomin Yan, Han Shen, Chao Wu
Journal: Journal of Infection (2020)
AB0440 LDL-CHOLESTEROL AS A RISK FACTOR OF PROGRESSION TO ESRD IN PATIENTS WITH LUPUS NEPHRITIS
Authors: D. J. Park, S. E. Choi, H. Xu, J. H. Kang, S. S. Lee
Journal: Annals of the Rheumatic Diseases (2020)

Background: Objectives: There are few data on the effect of dyslipidemia in patients with lupus nephritis (LN). Thus, we investigated the effect of low-density lipoprotein-cholesterol (LDL-C) on the progression to end-stage renal disease (ESRD) in patients with biopsy-proven LN. Methods: We followed 121 LN patients who underwent kidney biopsy and were subsequently treated with immunosuppressive drugs. Sociodemographic, clinical, laboratory (including lipid profile), and treatment-related data at the time of kidney biopsy and during follow-up were obtained by a review of patients’ charts. Patients were divided into two groups related to the mean LDL-C level: &lt;100 mg/dL and ≥100 mg/dL. Cox’s proportional regression analysis was performed to identify the independent predictors of progression to ESRD in LN patients. Results: Seventy-one of 121 biopsy-proven LN patients (58.7%) showed more than 100 mg/dL of LDL-C at the time of LN diagnosis. The higher LDL-C group excreted more 24-hour urine protein (p=0.003), and showed a higher proportion of proliferative LN (p=0.013) and an activity score &gt;12 (p=0.023). During a mean follow-up of 83.0 (range, 12–171) months, ESRD was more frequent in the higher LDL-C group than in the lower group (15.5% vs. 2.0%; p=0.012). In the multivariate Cox’s proportional regression analysis, LDL-C ≥100 mg/dL (hazard ratio [HR], 171.340; p=0.012), estimated glomerular filtration rate during the renal biopsy (HR, 0.977; p=0.005), statin exposure during follow-up (HR, 0.163; p=0.031), relapse (HR, 9.752; p=0.036), and complete remission at 1-year of treatment (HR, 0.034; p=0.003) were significant predictors of progression to ESRD in LN patients. Conclusion: Our findings suggest that dyslipidemia at the onset of LN is an independent risk factor for predicting the development of ESRD in LN patients. Therefore, lipid profile should be monitored carefully and managed aggressively to avoid the deterioration of kidney function in patients with LN. Disclosure of Interests: None declared
Risks for cold frequency vary by sex: role of asthma, age, TLR7 and leukocyte subsets
Authors: Liisa M. Murray, Stephanie T. Yerkovich, Manuel A. Ferreira, John W. Upham
Journal: European Respiratory Journal (2020)

Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men. To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables: toll-like receptor (TLR)7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-α, tumour necrosis factor and interleukin-12 production, and asthma were then examined that might explain cold frequency. People with asthma cases reported more colds per year (median 3 versus 2; p&lt;0.001) and had lower baseline TLR7 gene expression (odds ratio 0.12; p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (β=0.096, p=0.002), and younger age (β=−0.017, p&lt;0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (β=−0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; β=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (β=−1.4, p=0.036) and high body mass index (β=0.041, p=0.004). Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.
Lung- and Diaphragm-Protective Ventilation
Authors: Ewan C. Goligher, Martin Dres, Bhakti K. Patel, Sarina K. Sahetya, Jeremy R. Beitler, Irene Telias, Takeshi Yoshida, Katerina Vaporidi, Domenico Luca Grieco, Tom Schepens, Giacomo Grasselli, Savino Spadaro, Jose Dianti, Marcelo Amato, Giacomo Bellani, Alexandre Demoule, Eddy Fan, Niall D. Ferguson, Dimitrios Georgopoulos, Claude Guérin, Robinder G. Khemani, Franco Laghi, Alain Mercat, Francesco Mojoli, Coen A. C. Ottenheijm, Samir Jaber, Leo Heunks, Jordi Mancebo, Tommaso Mauri, Antonio Pesenti, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.
Low‐Density Neutrophils in Systemic Lupus Erythematosus
Authors: Sen Hee Tay, Teja Celhar, Anna‐Marie Fairhurst
Journal: Arthritis & Rheumatology (2020)

Patients with systemic lupus erythematosus ( SLE ) display increased numbers of immature neutrophils in the blood, but the exact role of these immature neutrophils is unclear. Neutrophils that sediment within the peripheral blood mononuclear cell fraction after density centrifugation of blood are generally defined as low‐density neutrophils ( LDN s). Far beyond antimicrobial functions, LDN s are emerging as decision‐shapers during innate and adaptive immune responses. Traditionally, neutrophils have been viewed as a homogeneous population. However, the various LDN populations identified in SLE to date are heterogeneously composed of mixed populations of activated mature neutrophils and immature neutrophils at various stages of differentiation. Controversy also surrounds the role of LDN s in SLE in terms of whether they are proinflammatory or polymorphonuclear myeloid‐derived suppressor cells. It is clear that LDN s in SLE can secrete increased levels of type I interferon ( IFN ) and that they contribute to the cycle of inflammation and tissue damage. They readily form neutrophil extracellular traps, exposing modified autoantigens and oxidized mitochondrial DNA , which contribute to autoantibody production and type I IFN signaling, respectively. Importantly, the ability of LDN s in SLE to perform canonical neutrophil functions is polarized, based on mature CD 10+ and immature CD 10− neutrophils. Although this field is still relatively new, multiomic approaches have advanced our understanding of the diverse origins, phenotype, and function of LDN s in SLE . This review updates the literature on the origin and nature of LDN s, their distinctive features, and their biologic roles in the immunopathogenesis and end‐organ damage in SLE .
Associations of Flavored e-Cigarette Uptake With Subsequent Smoking Initiation and Cessation
Authors: Abigail S. Friedman, SiQing Xu
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Several states have banned sales of flavored e-cigarettes, but evidence on the association between vaping flavors and subsequent smoking initiation and cessation is limited. <h3>Objective</h3> To evaluate whether new uptake of flavored e-cigarettes is more strongly associated with subsequent smoking initiation and cessation than uptake of unflavored e-cigarettes, separately for youths (12-17 years), emerging adults (18-24 years), and prime-age adults (25-54 years). <h3>Design, Setting, and Participants</h3> This cohort study conducted secondary data analyses of longitudinal survey data from waves 1 to 4 of the Population Assessment of Tobacco and Health Study (collected from 2013 to 2018). The analytic sample was limited to 17 929 respondents aged 12 to 54 years at wave 1 who completed at least 3 consecutive waves of the survey and did not use e-cigarettes at baseline. Data were collected from 2013 to 2018 and analyzed in February 2020. <h3>Exposures</h3> Flavored vs unflavored e-cigarette use reported in wave 2 of the Population Assessment of Tobacco and Health Study. <h3>Main Outcomes and Measures</h3> Binary indicators captured wave 3 smoking among 7311 youths and 4634 emerging adults who did not smoke at baseline (ie, initiation) and not smoking at wave 3 among 1503 emerging adults and 4481 prime-age adults who smoked at baseline (ie, cessation). Smoking status was based on having smoked in the past 30 days for youths and established smoking (ie, current smoking among those who smoked at least 100 cigarettes in their lifetime) for emerging and prime-age adults. <h3>Results</h3> The youths who did not smoke at baseline, emerging adults who smoked at baseline, and prime-age adults who smoked at baseline consisted of 51.4% to 58.0% male participants and 66.9% to 77.0% white individuals. Vaping uptake was positively associated with smoking initiation in youth (adjusted odds ratio [AOR], 6.75; 95% CI, 3.93-11.57;<i>P</i> &lt; .001) and in emerging adults (AOR, 3.20; 95% CI, 1.70-6.02;<i>P</i> &lt; .001). Vaping uptake was associated with cessation in adults (AOR, 1.34; 95% CI, 1.02-1.75;<i>P</i> = .03). Vaping nontobacco flavors was no more associated with youth smoking initiation than vaping tobacco-flavors (AOR in youth, 0.66; 95% CI, 0.16-2.76;<i>P</i> = .56) but was associated with increased adult smoking cessation (AOR in adults, 2.28; 95% CI, 1.04-5.01;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> In this study, adults who began vaping nontobacco-flavored e-cigarettes were more likely to quit smoking than those who vaped tobacco flavors. More research is needed to establish the relationship between e-cigarette flavors and smoking and to guide related policy.
特应性湿疹的治疗 (TREAT) 登记工作组:比较 Dupilumab 与其他全身药物治疗中度至重度湿疹安全性的方法
Authors: A.L. Bosma, P.I. Spuls, I. Garcia‐Doval, L. Naldi, D. Prieto‐Merino, F. Tesch, C.J. Apfelbacher, B.W.M. Arents, S. Barbarot, E. Baselga, M. Deleuran, L.F. Eichenfield, L.A.A. Gerbens, A.D. Irvine, A. Manca, P. Mendes‐Bastos, M.A. Middelkamp‐Hup, A. Roberts, J. Seneschal, Å. Svensson, J.P. Thyssen, T. Torres, F.M. Vermeulen, C. Vestergaard, L.B. Kobyletzki, D. Wall, S. Weidinger, J. Schmit, C. Flohr
Journal: British Journal of Dermatology (2020)

特应性湿疹(也称为“特应性皮炎”或简称“湿疹”)是一种常见的皮肤病。大多数患有特应性湿疹的人可以通过局部治疗(直接涂抹在皮肤上)来控制湿疹,比如润肤剂和局部皮质类固醇。 然而,一些患有中度至重度疾病的患者,不能用这些疗法很好地治疗疾病。这些人需要使用片剂或注射剂进行全身药物治疗(作用于全身的治疗),以有效减轻他们的症状。 Dupilumab 是一种新的全身性药物 (自 2018 年以来), 用于治疗中度至重度湿疹患者。它已经在美国和欧盟获批用于治疗 12 岁或以上的患者。 为了比较 Dupilumab 与其他全身药物治疗的安全性,研究人员需要所有这些药物在实际应用中的安全性数据。TREAT 登记工作组的登记处收集了所有全身药物治疗特应性湿疹的有效性和安全性的数据。英国、爱尔兰、美国、德国、荷兰、丹麦、瑞典、法国、意大利、西班牙和葡萄牙等国家都参与了 TREAT。所有这些国家都以相同的方式收集数据,因此数据具有可比性。 这篇文章描述了如何使用所有这些国际数据来比较 Dupilumab 与其他全身药物治疗安全性的研究方案。这对医生和患者都很重要,这可以让他们在知情的情况下决定哪种治疗对他们来说是最好的。 本摘要涉及研究: 特应性湿疹的治疗 (TREAT) 登记工作组: 一项针对特应性湿疹患者中 Dupilumab 和其他全身药物疗法的欧洲安全性研究的研究方案
CXCR7 and CXCR3 interactions promote breast cancer (BrCa) cell migration, adhesion and survival
Authors: LaSharon Mosley, Praveen Sharma, Rajesh Singh, Shailesh Singh, James Lillard
Journal: Cancer Research (2008)

5334  Metastasis is responsible for all breast cancer (BrCa)- related deaths; therefore, therapies designed to prevent the spread of BrCa cells are greatly needed. The reasons why breast carcinomas preferentially metastasize to lymph nodes, bone, brain and lung are not fully understood. Similarly, the anti-apoptotic mechanisms employed by BrCa cells to survive in serum-free environments and apoptosis-inducing therapeutics are numerous and contribute significantly to the morbidity and mortality of this disease. Chemokines have been demonstrated to support BrCa metastasis and may also activate anti-apoptotic mechanisms. In this regard, BrCa cells express functionally active CXCR3, CXCR4 and CXCR7 to presumably support adhesion, invasion, and cell survival. The ligands for CXCR7 are CXCL11 (which also binds CXCR3) and CXCL12 (which also binds CXCR4); calcitonin-gene related peptide (CGRP) and adrenomedullin (AM) have also been suggested as potential CXCR7 ligands, which is somewhat controversial since these bioactive peptides have been definitively shown to bind class B G-protein coupled receptors (GPCRs) and not chemokine receptors (class A GPCRs). Nevertheless, these ligands are expressed by activated stroma as well as vascular and lymphatic endothelial cells, which might support motility, adherence and survival of BrCa cells. Indeed, all of these potential CXCR7 ligands are elevated in tissue and serum from patients with a variety of systemic diseases, including BrCa. We provide evidence that breast cancer cell lines express CXCR7 and its expression correlates with disease stage. We also confirm that this receptor; along with CXCR3 and CXCR4, are expressed by BrCa cell lines. We further show that CXCR7 is responsive to CXCL11, CXCL12, and adrenomedullin, but not CGRP. Lastly, for the first time to our knowledge, we demonstrate that CXCL11 and AM lead to rapid CXCR3 desensitization on BrCa cells, while CXCL11, CXCL12, and AM differentially modulates CXCR7 clustering on BrCa cell lines. Taken together, these studies provide important and novel information regarding the cellular and molecular mechanisms involved in CXCR3- and CXCR7-mediated breast cancer metastasis.
Covid-19: Hydroxychloroquine was ineffective as postexposure prophylaxis, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

<h3>AIMS</h3> To determine whether home intervention by a specialist health visitor affects the outcome of children with failure to thrive. <h3>METHODS</h3> Children referred for failure to thrive were randomised to receive conventional care, or conventional care and additional specialist home visiting for 12 months. Outcomes measured were growth, diet, use of health care resources, and Bayley, HAD (hospital anxiety and depression), and behavioural scales. <h3>RESULTS</h3> Eighty three children, aged 4–30 months, were enrolled, 42 received specialist health visitor intervention. Children in both groups showed good weight gain (mean (SD) increase in weight SD score for the specialist health visitor intervention group 0.59 (0.63) <i>v</i>0.42 (0.62) for the control group). Children &lt; 12 months in the intervention group showed a higher mean (SD) increase in weight SD score than the control group (0.82 (0.86) <i>v</i>0.42 (0.79)). Both groups improved in developmental score and energy intake. No significant differences were found for the primary outcome measures, but controls had significantly more dietary referrals, social service involvement, and hospital admissions, and were less compliant with appointments. <h3>CONCLUSIONS</h3> The study failed to show that specialist health visitor intervention conferred additional benefits for the child. However, the specialist health visitor did provide a more coordinated approach, with significant savings in terms of health service use. Problems inherent to health service research are discussed.
BRAF-Mutated Erdheim-Chester Disease: Profound Response to Vemurafenib Visualized With Serial Multimodality Imaging
Authors: Javaughn Corey R. Gray, Jongho Kim, Michael Digianvittorio, Nancy K. Feeley, Paul J. Scheel, Stanley S. Siegelman, Elliot K. Fishman, Steven P. Rowe
Journal: Journal of the National Comprehensive Cancer Network (2020)

Erdheim-Chester disease (ECD) is an extremely rare and aggressive non-Langerhans histiocytic disorder. ECD typically presents with bone pain in middle-aged adults, although some patients present with multisystem disease involving the skeleton, central nervous system, cardiovascular system, lungs, and other disease sites. The etiology of ECD is currently unknown, but it is thought to be a reactive or neoplastic disorder. Recently, mutation of the BRAF gene has been found in &gt;50% of ECD cases, and this gene has become a therapeutic target for patients with ECD. Vemurafenib, a BRAF inhibitor, has been approved by the FDA for treatment of ECD. This report presents an elderly male patient with an aggressive phenotype of ECD and highlights the utility of multimodality imaging in monitoring the clinical course and disease response to treatment with vemurafenib.
Abstract 13475: Clinical Assessment of AT-001, an Aldose Reductase Inhibitor in Development for Diabetic Cardiomyopathy: A 28-Day Proof of Concept Study
Authors: Riccardo Perfetti, Shoshana Shendelman
Journal: Circulation (2019)

Diabetes is an independent risk factor for heart disease and Diabetic Cardiomyopathy (DbCM) has been associated with the development of heart failure. Epidemiological studies have demonstrated that...
Abstract 16411: CTRP1 Promotes Vasodilatory Dysfunction by Increasing Nitric Oxide Synthase Dysfunction Through Adipo-Vascular Axis
Authors: Xiao Qun Wang, Zhu Hui Liu, Jia Wei Chen, Chang Li, Xin Yi Shu, Ying Shen, Rui Yan Zhang, Wei Feng Shen, Lin Lu
Journal: Circulation (2019)

Introduction: C1q/TNF-related protein (CTRP) 1 is a newly identified adipocytokine with identical structural domains of adiponectin but displaying distinct functions. We previously showed that CTRP...
AB0031 T HELPER 17 CELLS WERE SIGNIFICANTLY DECREASED BY MITOCHONDRIAL ELECTRON TRANSPORT CHAIN COMPLEX INHIBITOR IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: H. R. Lee, S. J. Yoo, J. Kim, I. S. Yoo, C. K. Park, S. W. Kang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RA Objectives: To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors. Methods: Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining. Results: The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1&gt;DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased. Conclusion: The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production. References: [1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9. [2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8. Disclosure of Interests: None declared