tbuckley/cabot-search huggingface dataset:
ETV4 promotes late development of prostatic intraepithelial neoplasia and cell proliferation through direct and p53-mediated downregulation of p21
Authors: Irene Cosi, Annamaria Pellecchia, Emanuele De Lorenzo, Eugenio Torre, Michela Sica, Gabriella Nesi, Rosario Notaro, Maria De Angioletti
Journal: Journal of Hematology & Oncology (2020)

Abstract Background ETV4 is one of the ETS proteins overexpressed in prostate cancer (PC) as a result of recurrent chromosomal translocations. In human prostate cell lines, ETV4 promotes migration, invasion, and proliferation; however, its role in PC has been unclear. In this study, we have explored the effects of ETV4 expression in the prostate in a novel transgenic mouse model. Methods We have created a mouse model with prostate-specific expression of ETV4 (ETV4 mice). By histochemical and molecular analysis, we have investigated in these engineered mice the expression of p21, p27, and p53. The implications of our in vivo findings have been further investigated in human cells lines by chromatin-immunoprecipitation (ChIP) and luciferase assays. Results ETV4 mice, from two independent transgenic lines, have increased cell proliferation in their prostate and two-thirds of them, by the age of 10 months, developed mouse prostatic intraepithelial neoplasia (mPIN). In these mice, cdkn1a and its p21 protein product were reduced compared to controls; p27 protein was also reduced. By ChIP assay in human prostate cell lines, we show that ETV4 binds to a specific site (-704/-696 bp upstream of the transcription start) in the CDKN1A promoter that was proven, by luciferase assay, to be functionally competent. ETV4 further controls CDKN1A expression by downregulating p53 protein: this reduction of p53 was confirmed in vivo in ETV4 mice. Conclusions ETV4 overexpression results in the development of mPIN but not in progression to cancer. ETV4 increases prostate cell proliferation through multiple mechanisms, including downregulation of CDKN1A and its p21 protein product: this in turn is mediated through direct binding of ETV4 to the CDKN1A promoter and through the ETV4-mediated decrease of p53. This multi-faceted role of ETV4 in prostate cancer makes it a potential target for novel therapeutic approaches that could be explored in this ETV4 transgenic model.
The dilemma of COVID-19 recurrence after clinical recovery
Authors: Marco Bongiovanni, Marco Vignati, Giuseppe Giuliani, Giampiero Manes, Stefania Arienti, Loris Pelucchi, Nicoletta Cattaneo, Bruno Dino Bodini, Danila Clerici, Fabio Rosa, Lucienne Pellegrini, Mario Schettino, Desiree Picascia, Francesco Bini
Journal: Journal of Infection (2020)
The characteristics and impact of pruritus in adult dermatology patients: A prospective, cross-sectional study
Authors: Tomasz Hawro, Katarzyna Przybyłowicz, Max Spindler, Marlena Hawro, Michał Steć, Sabine Altrichter, Karsten Weller, Markus Magerl, Ulrich Reidel, Ezzat Alarbeed, Ola Alraboni, Marcus Maurer, Martin Metz
Journal: Journal of the American Academy of Dermatology (2020)
Social hallmarks of aging: Suggestions for geroscience research
Authors: Eileen M. Crimmins
Journal: Ageing Research Reviews (2020)

This paper focuses on the social hallmarks of aging including low lifetime socioeconomic status, adversity in childhood and adulthood, being a member of a minority group, adverse health behaviors, and adverse psychological states. The "Social Hallmarks of Aging" are analogous to the "Geroscience Hallmarks of Aging" in reflecting a set of underlying and interrelated social causes of multiple age-related health outcomes. The paper presents empirical work incorporating the social hallmarks of aging with indicators of multiple biological hallmarks of aging as well as downstream biology in explaining a range of health outcomes. Results show the relative strength of the associations of social and biological measures with important health outcomes. Social factors are strongly related to physical and cognitive functioning and multimorbidity in this older population; this remains true when the significant number of biological measures are controlled. These results can be interpreted to mean that a significant amount of the social variance in age-related health outcomes is not explained by these measures of biology. Indicators of the geroscience hallmarks of aging only relate modestly to the variability in human health outcomes. Attention to the social hallmarks related to human aging can usefully be incorporated into work on the biological hallmarks of aging to make greater progress in understanding human aging.
Covid-19: Nearly 6% of people in England were infected by end of June, study suggests
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Covid-19: Nearly 6% of people in England were infected by end of June, study suggests Gareth Iacobucci Some 3.4 million people in England-just under 6% of the population-are likely to have been infected with covid-19 by the end of June, a large antibody surveillance study has found.
Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates
Authors: Jongjin Park, Na Geum Lee, Mihee Oh, Jinhoi Song, Wooil Kim, Min-Gi Kwon, Seul Gi Kim, Baek Soo Han, Kwang-Hee Bae, Dong Gwang Lee, Sang-Hyun Lee, Jong-Gil Park, Jae Ho Kim, Jangwook Lee, Jeong-Ki Min
Journal: Biomaterials (2020)
Increased mortality in HIV/HCV-coinfected compared to HCV-monoinfected patients in the DAA era due to non-liver-related death
Authors: Mathieu Chalouni, Stanislas Pol, Philippe Sogni, Hélène Fontaine, Karine Lacombe, Jean Marc-Lacombe, Laure Esterle, Celine Dorival, Marc Bourlière, Firouzé Bani-Sadr, Victor de Ledinghen, David Zucman, Dominique Larrey, Dominique Salmon, Fabrice Carrat, Linda Wittkop, D. Salmon, L. Wittkop, P. Sogni, L. Esterle, P. Trimoulet, J. Izopet, L. Serfaty, V. Paradis, B. Spire, P. Carrieri, M.A. Valantin, G. Pialoux, J. Chas, I. Poizot-Martin, K. Barange, A. Naqvi, E. Rosenthal, A. Bicart-See, O. Bouchaud, A. Gervais, C. Lascoux-Combe, C. Goujard, K. Lacombe, C. Duvivier, D. Neau, P. Morlat, F. Bani-Sadr, L. Meyer, F. Boufassa, B. Autran, A.M. Roque, C. Solas, H. Fontaine, D. Costagliola, L. Piroth, A. Simon, D. Zucman, F. Boué, P. Miailhes, E. Billaud, H. Aumaitre, D. Rey, G. Peytavin, V. Petrov-Sanchez, D. Lebrasseur-Longuet
Journal: Journal of Hepatology (2020)
Severe Hypoglycemia Linked With Over-the-Counter Supplement
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Consent for elective surgery during covid-19: personalise information
Authors: James Henderson
Journal: BMJ (2020)

I read with delight the article by Sokol and Dattani on how surgeons should seek consent for elective surgery during the pandemic.1 I had been struggling with this matter for weeks, in the absence of formal guidance and under pressure to restart elective work and reduce the waiting list.

The Royal College of Surgeons of England (RCSEng) …
Genetic characterization of a highly pathogenic H5N6 avian influenza virus isolated from greylag goose
Authors: Wenming Jiang, Zhixin Li, Shuo Liu, Jinping Li, YuMei Wang, Jie Li, Cheng Peng, Quanru Song, Lin Zhang, Fuyou Zhang, Xiaoliang Wang, Hualei Liu
Journal: Journal of Infection (2020)
Abstract 17: MBQ-167, a Rac/Cdc42 targeted therapeutic, in combination with paclitaxel for TNBC treatment
Authors: Jean Ruiz-Calderon, Irmaris Lopez-Lopez, Ailed Cruz-Collazo, Suranganie Dharmawardhane
Journal: Clinical Cancer Research (2020)

Abstract Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally advanced and metastatic cancer. While targeted therapies for TNBC are in various stages of development, current standard chemotherapies include taxanes such as paclitaxel and anthracycline agents. With the objective of specifically targeting invasive cancer, our group has been developing small-molecule inhibitors of the Rho GTPases Rac and Cdc42, which are known drivers of cancer cell invasion and metastasis. Of these, MBQ-167 inhibits both Rac and Cdc42 with IC50s of 103 and 78 nmol/L, respectively, and consequently inhibits p21-activated kinase (PAK) signaling, metastatic cancer cell proliferation, migration, tumor growth, and metastasis (Humphries-Bickley et al., Mol Cancer Ther 2017). We found that in addition to blocking HER2-type breast cancer progression, MBQ-167 is also highly effective against TNBC cell and tumor growth, as well as metastasis in mouse models. The purpose of this study was to test the efficacy of MBQ-167 in combination with the current chemotherapeutic paclitaxel. We hypothesized that the combination of paclitaxel and MBQ-167 is a rational strategy to inhibit tumor growth and metastasis in TNBC. To test this hypothesis, we administered a nontoxic dosage of individual MBQ-167, paclitaxel, or combined MBQ-167 and paclitaxel to immunocompromised mice bearing mammary fat pad tumors from GFP-tagged MDA-MB-468 or MDA-MB-231 human TNBC cells. Tumor growth was monitored weekly and metastasis was quantified at the end of the study. Treatment with MBQ-167 and/or paclitaxel resulted in reduced tumor growth by 70-80% in both models. In the MDA-MB-231 model, MBQ-167 paralleled paclitaxel treatment with a modest benefit in combined therapy. However, in the epidermal growth factor receptor (EGFR)-positive TNBC model MDA-MB-468, MBQ-167 alone or in combination significantly reduced metastasis to the lungs and spleen, while paclitaxel alone increased metastasis to the liver, lungs, and spleen. These results show that MBQ-167 is a promising antimetastatic agent that can be effective in combination with current chemotherapeutic agents. Citation Format: Jean Ruiz-Calderon, Irmaris Lopez-Lopez, Ailed Cruz-Collazo, Suranganie Dharmawardhane. MBQ-167, a Rac/Cdc42 targeted therapeutic, in combination with paclitaxel for TNBC treatment [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 17.
Molecular mechanisms and therapeutic implications of tetrandrine and cepharanthine in T cell acute lymphoblastic leukemia and autoimmune diseases
Authors: Wencheng Xu, Shuhe Chen, Xiaoqin Wang, Sachiko Tanaka, Kenji Onda, Kentaro Sugiyama, Haruki Yamada, Toshihiko Hirano
Journal: Pharmacology & Therapeutics (2020)
Neoadjuvant and Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A 2020 Systematic Review and Meta-analysis, and Future Perspectives on Systemic Therapy
Authors: Jeffrey J. Leow, Yew Lam Chong, Steven L. Chang, Begoña P. Valderrama, Thomas Powles, Joaquim Bellmunt
Journal: European Urology (2020)
AB0002 INCREASED SENSITIVITY TO DNA DAMAGING AGENTS IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Olga Brzezińska, Grzegorz Galita, Anna Macieja, Anna Lewandowska-Polak, Joanna Sarnik, Tomasz Popławski, Joanna Makowska
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disorder with not fully elucidate pathogenesis. Rheumatoid arthritis patients have increased risk of developing lymphomas. One of the possible mechanisms of this predisposition is increased genomic instability and impaired DNA repair. It is unclear how this genomic instability contributes to diseases pathogenesis. <h3>Objectives:</h3> The aim of this study was to analyze the sensitivity and repair efficiency of mononuclear cells isolated from RA patients to DNA damaging agents. <h3>Methods:</h3> The study group consisted of 22 patients with RA (age years - 60,77±13,00 women-17, men - 5) hospitalized in the Department of Rheumatology between 2017 and 2018 and 10 healthy controls without autoimmune and oncological diseases in clinical history (age 44,09±16,56; women-5, men-6). The peripheral blood mononuclear cells (PBMC) from all subjects were isolated. Using comet assay the degree of intracellular DNA damage as a result of exposure to standard damage factors: tert-butyl hydroperoxide (TBH), bleomycin, methyl methanesulfonate (MMS) and UV radiation was assessed. <h3>Results:</h3> RA patients show a statistically significant higher level of endogenous damage in PBMC DNA than controls (mean RA- 8,64% vs 4,68% in control; p&lt;0,001). The extent of the DNA damage induced by TBH, MMS as well as UV was significantly higher in PBMC derived from RA patients than in healthy counterparts (p&lt;0,001). The DNA of RA patients treated with TBH was repaired less effectively than in control (p&lt;0,0001). Significantly higher percentage of DNA damage in RA DNA (p&lt;0,0001) under the influence of bleomycin and clearly marked repair processes were observed. Among the healthy controls lower percentage of DNA was damaged, and although the repair process was slower but the final percent of DNA damage was lower than in RA cases (p&lt;0,0001). <h3>Conclusion:</h3> DNA of people with rheumatoid arthritis is significantly more susceptible to damage in baseline and induced. The kinetics of DNA repair from RA patients after the introduction (TBH and bleomycin) was statistically less effective as compared to healthy control. Understanding the ethology of this phenomenon in RA may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. <h3>Acknowledgement:</h3> The project is financed under the funds of the National Science Center (2017/25/B/NZ6/01358) <h3>Disclosure of Interests:</h3> None declared
Taking into account the wider evolutionary context of cumulative cultural evolution
Authors: Nicolas Claidière
Journal: Behavioral and Brain Sciences (2020)

Abstract The target article reviews evidence showing that technological reasoning is crucial to cumulative technological culture but it fails to discuss the implications for the emergence of cumulative cultural evolution (CCE) in general. The target article supports the social view of CCE against the more ecological alternative and suggests that CCE appears when specialised individual-learning mechanisms evolve.
OP0336-HPR RISK FACTORS FOR PERSISTENCE AND DEVELOPMENT OF FREQUENT MUSCULOSKELETAL PAIN IN ADOLESCENT ATHLETES
Authors: J. S Malmborg, A. Bremander, S. Bergman, E. Haglund, M. C. Olsson
Journal: Annals of the Rheumatic Diseases (2020)

Background: Physical activity has a positive impact on health, but adolescent athletes often report musculoskeletal pain (MP) which is negative in the aspect of sustaining physical activity over time. There is a lack of longitudinal assessments of MP and potential risk factors, such as timing of physical maturation, in adolescent athletes. Objectives: To identify risk factors associated with the persistence or development of frequent MP at a 2-year follow-up in adolescent sport school students. Methods: Fourteen-year-old sport school students (n=233) were invited to participate in this 2-year longitudinal study. Self-reports of MP was assessed as frequency, distribution, and intensity, and health status by EQ-5D. Physical maturation was calculated by the Mirwald equation (height, weight, and sitting height) (1), and categorized as early (&gt;1 year), average (±1 year), or late (&lt;–1 year). Students were grouped at baseline and follow-up into infrequent (never to monthly) or frequent (weekly to daily) MP groups. Logistic regression analysis was used to study associations between frequent MP at follow-up and baseline variables. Results: 131 students (79 boys and 52 girls) were included in the study. Development or persistence of frequent MP at follow-up (n=61) was associated with being a girl, late physical maturation (only boys were categorized as late), non-contact sports participation, frequent MP at baseline, and reporting ≥2 MP sites at baseline. Students with a better health status at baseline were less likely to belong to the frequent MP group at follow-up (Table). Conclusion: Frequent MP is common in sport school students. MP in young athletes may become a future health problem and there is a need for recognition and interventions by coaches and health services to prevent MP from becoming persistent. References: [1]Mirwald, R. L., Baxter-Jones, A. D., Bailey, D. A., &amp; Beunen, G. P. (2002). An assessment of maturity from anthropometric measurements. Med Sci Sports Exerc, 34 (4), 689-694. Table. Associations between background variables at baseline and frequent MP at follow-up based on crude logistic regression analysis controlling each variable for sex. Baseline variables Model Infrequent MP vs. Frequent MP OR (95% CI; p-value) Sex Boys 1.00 Girls 2.76 (1.34–5.68; p&lt;0.01) Physical maturation Average (±1 year) 1.00 Early (&gt;1 year) 0.41 (0.05–3.65; p=0.42) Late (&lt;–1 year) 3.83 (1.13–12.95; p=0.03) Sport categories Contact 1.00 Non-contact 5.16 (2.07–12.88; p&lt;0.001) MP groups Infrequent 1.00 Frequent 2.74 (1.31–5.72; p&lt;0.01) MP intensity last week (NRS 0–10, best to worst) 1.15 (0.98–1.35; p=0.10) Number of MP sites 0 1.00 1 2.32 (0.71–7.58; p=0.16) ≥2 2.87 (1.32–6.25; p&lt;0.01) EQ-5D (0.00–1.00, worst to best) 0.03 (0.001–0.58; p=0.02) Disclosure of Interests: None declared
Abstract 13986: Beta-blocker Therapy Reduces Adverse Aorta-Related Events in Patients With Type B Acute Aortic Intramural Hematoma
Authors: Masaki Nakashima, Shuichiro Kaji, Ryosuke Murai, Yasuhiro Sasaki, Mitsuhiko Ota, Kitae Kim, Takafumi Yamane, Takeshi Kitai, Atsushi Kobori, Makoto Kinoshita, Yutaka Furukawa
Journal: Circulation (2016)

Background: Optimal medical therapy is widely accepted as a first line therapy for patients with type B acute aortic intramural hematoma (B-IMH). Beta-blocker therapy is supposed to be effective for prevention of aortic dilatation by decreasing aortic wall stress. However, benefits of beta-blocker therapy have not been rigorously shown in B-IMH compared with type B acute aortic dissection with patent false lumen. The purpose of this study was to assess the association of beta-blocker therapy and clinical outcomes in B-IMH patients. Methods and Results: A total of 193 consecutive acute B-IMH patients admitted to our hospital and discharged alive were retrospectively analyzed. The mean age was 71±10 years and 124 (64%) patients were men. Of the 193 patients, 165 patients (85%) were treated with beta-blocker therapy at discharge. We compared the incidence of aorta-related adverse events, a composite of end-organ or limb ischemia, aortic rupture, recurrent dissection, aortic expansion ≥5 mm, and aortic surgery, between the patients with and without beta-blocker therapy. During a mean follow up of 4.2years, 16 of 165 (9.7%) patients with beta-blocker therapy developed aorta-related adverse events, whereas 8 of 28 (29%) patients without beta-blocker therapy developed aorta-related adverse events (p&lt;0.001). A multivariate Cox regression analysis adjusted for age, gender and prevalence of hypertension indicated that beta-blocker therapy was associated with a significantly reduced risk for aorta-related adverse events (hazard ratio=0.33, 95% confidence interval: 0.14-0.83, p=0.02). Conclusions: Beta-blocker therapy was associated with a significantly reduced risk for aorta-related adverse events in patients with type B acute aortic intramural hematoma.
Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study
Authors: Jianfeng Xie, Wenjuan Wu, Shusheng Li, Yu Hu, Ming Hu, Jinxiu Li, Yi Yang, Tingrong Huang, Kun Zheng, Yishan Wang, Hanyujie Kang, Yingzi Huang, Li Jiang, Wei Zhang, Ming Zhong, Ling Sang, Xia Zheng, Chun Pan, Ruiqiang Zheng, Xuyan Li, Zhaohui Tong, Haibo Qiu, Bin Du
Journal: Intensive Care Medicine (2020)
A Pathophysiological Perspective on the SARS‐CoV‐2 Coagulopathy
Authors: Nuray Kusadasi, Maaike Sikma, Albert Huisman, Jan Westerink, Coen Maas, Roger Schutgens
Journal: HemaSphere (2020)

Abstract Recent evidence is focusing on the presence of a hypercoagulable state with development of both venous and arterial thromboembolic complications in patients infected with SARS‐CoV‐2. The ongoing activation of coagulation related to the severity of the illness is further characterized by thrombotic microangiopathy and endotheliitis. These microangiopathic changes cannot be classified as classical disseminated intravascular coagulation (DIC). In this short review we describe the interaction between coagulation and inflammation with focus on the possible mechanisms that might be involved in SARS‐CoV‐2 infection associated coagulopathy in the critically ill.
Therapeutic potential of phenylethanoid glycosides: A systematic review
Authors: Lipeng Wu, Milen I. Georgiev, Hui Cao, Lutfun Nahar, Hesham R. El‐Seedi, Satyajit D. Sarker, Jianbo Xiao, Baiyi Lu
Journal: Medicinal Research Reviews (2020)

Abstract Phenylethanoid glycosides (PhGs) are generally water‐soluble phenolic compounds that occur in many medicinal plants. Until June 2020, more than 572 PhGs have been isolated and identified. PhGs possess antibacterial, anticancer, antidiabetic, anti‐inflammatory, antiobesity, antioxidant, antiviral, and neuroprotective properties. Despite these promising benefits, PhGs have failed to fulfill their therapeutic applications due to their poor bioavailability. The attempts to understand their metabolic pathways to improve their bioavailability are investigated. In this review article, we will first summarize the number of PhGs compounds which is not accurate in the literature. The latest information on the biological activities, structure–activity relationships, mechanisms, and especially the clinical applications of PhGs will be reviewed. The bioavailability of PhGs will be summarized and factors leading to the low bioavailability will be analyzed. Recent advances in methods such as bioenhancers and nanotechnology to improve the bioavailability of PhGs are also summarized. The existing scientific gaps of PhGs in knowledge are also discussed, highlighting research directions in the future.
Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation
Authors: Kyung Won Kim, Sang-Cheol Park, Hyung-Ju Cho, Haerin Jang, Jaehyun Park, Hyo Sup Shim, Eun Gyul Kim, Mi Na Kim, Jung Yeon Hong, Yoon Hee Kim, Sanghun Lee, Scott T. Weiss, Chang-Hoon Kim, Sungho Won, Myung Hyun Sohn
Journal: Journal of Allergy and Clinical Immunology (2020)