tbuckley/cabot-search huggingface dataset:
Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis
Authors: Yang Ye, Jian He, Yue Qiao, Yuchen Qi, Hongbo Zhang, Hélder A. Santos, Danni Zhong, Wanlin Li, Shiyuan Hua, Wei Wang, Andrzej Grzybowski, Ke Yao, Min Zhou
Journal: Theranostics (2020)

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation.It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects.Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery.The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag + and Cu + ) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects.The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation.In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model.Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo.Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction.Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball.Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure.Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.
Dissection of mucosa and muscularis mucosa instead of submucosal dissection: rapid retroflow of the injection fluid can be an indicator
Authors: Süleyman Günay, Elif SarıtaşYüksel, Firdevs Topal, Betül Paköz, Cem Çekiç, Hakan Çamyar, Sezgin Vatansever
Journal: Endoscopy (2020)

Peroral endoscopic myotomy (POEM) in sigmoid achalasia is a cumbersome technique even in trained hands. "Difficult POEM" is a new terminology associated with complex achalasia [1 – 3]. Several complications can occur during difficult POEM, including inability to make a tunnel incision due to submucosal fibrosis, disorientation, mucosal perforation, or detachment of clips, which is associated with mucosal infection on the edges of the tunnel.
Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, on Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial
Authors: Julio Rosenstock, Antonio Nino, Joseph Soffer, Lois Erskine, Andre Acusta, Jo Dole, Molly C. Carr, Jason Mallory, Philip Home
Journal: Diabetes Care (2020)

The principle of replacing prandial insulin lispro with a once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) for type 2 diabetes inadequately controlled on a multiple daily insulin injections regimen was tested with albiglutide.In this treat-to-target study, basal plus prandial insulin was optimized over 4 weeks before participants were randomized (1:1) to albiglutide plus optimized basal insulin glargine and lispro (dose reduced by 50% at randomization; subsequently, lispro injections were fully discontinued 4 weeks later) (n = 402) or to continued optimized lispro plus optimized glargine (n = 412).Mean ± SD HbA1c at baseline, 7.8 ± 0.6% (61 ± 7 mmol/mol) in the albiglutide + glargine group and 7.7 ± 0.6% (60 ± 7 mmol/mol) in the lispro + glargine group, was reduced at week 26 to 6.7 ± 0.8% (49 ± 8 mmol/mol) and 6.6 ± 0.8% (48 ± 8 mmol/mol), respectively (least squares [LS] difference 0.06% [95% CI -0.05 to 0.17]; noninferiority P < 0.0001). In the albiglutide + glargine group, 218 participants (54%) replaced all prandial insulin without reintroducing lispro up to week 26. Total daily prandial insulin dose was similar at baseline but was lower by 62 units/day (95% CI -65.9 to -57.8; P < 0.0001) at week 26 in the albiglutide + glargine group, and the total number of weekly injections was also reduced from 29 to 13 per week. Less severe/documented symptomatic hypoglycemia (57.2% vs. 75.0%) occurred in the albiglutide + glargine group with meaningful weight differences (LS mean ± SE -2.0 ± 0.2 vs. +2.4 ± 0.2 kg; P < 0.0001) vs. lispro + glargine. Gastrointestinal adverse events were higher with albiglutide + glargine (26% vs. 13%).A once-weekly GLP-1RA was able to substitute for prandial insulin in 54% of people, substantially reducing the number of prandial insulin injections; glycemic control improved, with the added benefits of weight loss and less hypoglycemia in the GLP-1RA arm. Replacing prandial insulin with a weekly GLP-1RA can simplify basal plus prandial insulin treatments and achieve better outcomes in type 2 diabetes.
US decision to pull out of World Health Organization
Authors: Devi Sridhar, Lois King
Journal: BMJ (2020)

1 that the US would withdraw from the World Health Organization came as little surprise to those who had been following his administration's attempts to find a scapegoat for the covid-19 crisis.The attacks on WHO have to be seen within a larger geopolitical context of increasing tension and blame between the US and China, with WHO caught in the middle like a child not wanting to pick sides between warring parents. 2 But are these attacks fair, and what will US
Screening of small molecule inhibitors of the Fanconi Anemia-BRCA pathway
Authors: Toshiyasu Taniguchi, Maria Vasserman, Deborah S. Chirnomas, Alan D. D’Andrea
Journal: Cancer Research (2005)

4995  Fanconi anemia (FA) is a cancer-susceptibility syndrome characterized by hypersensitivity to DNA crosslinking agents, such as cisplatin and mitomycin C. All 9 known FA proteins cooperate with breast/ovarian cancer susceptibility gene products (BRCA1 and BRCA2) in a common DNA damage-activated signaling pathway called the Fanconi anemia(FA)-BRCA pathway. Seven FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) are components of a multi-subunit ubiquitin ligase complex (FA complex) required for monoubiquitination of FANCD2. After DNA damage, FANCD2 is monoubiquitinated and targeted to BRCA1/BRCA2-containing nuclear foci in an ATR kinase-dependent fashion. Importantly, the pathway is inactivated in a wide variety of human cancers by methylation of the FANCF gene. This inactivation causes cisplatin sensitivity in some ovarian cancer cell lines, suggesting an important role of the pathway in cisplatin sensitivity of human tumors. We hypothesized that inhibitors of the FA-BRCA pathway will sensitize cancer cells to cisplatin and, therefore, may be useful for the treatment of cisplatin-resistant cancer. We developed a high-throughput small molecule screen using cells harboring a Green Fluorescent Protein tagged FANCD2 (GFP-FANCD2) and assaying for GFP-FANCD2 nuclear foci formation as a readout, because FANCD2 foci formation is a surrogate marker of the integrity of the pathway. We plated cells with GFP-FANCD2 onto 384-well plates, added small molecules, gamma-irradiated the cells and scored the GFP-FANCD2 nuclear foci. Wells lacking GFP-FANCD2 nuclear foci were scored as positive. We have screened more than 5000 chemicals so far, and found 30 positive chemicals, including kinase inhibitors (wortmannin, H-9, alsterpaullone), geldanamycin, and curcumin. We also found that wortmannin, H-9, and alsterpaullone inhibit ATR-dependent phosphorylation of Chk1. These results together with our previous finding that ATR is required for the activation of the pathway suggest that these drugs inhibit the pathway through inhibition of ATR. Furthermore, we confirmed that alsterpaullone sensitized an ovarian cancer cell line in an FA-BRCA pathway-dependent manner. These findings support the rationale for further screening for FA-BRCA pathway inhibitors.
Retinoic acid inhibits growth of immortalized and weakly tumorigenic human breast epithelial cells (HBEC), but not highly tumorigenic HBEC: Molecular mechanisms of loss of anti-proliferative effect of retinoic acid during breast carcinogenesis
Authors: Eun Hyun Ahn, Chia-Cheng Chang, David A. Talmage
Journal: Cancer Research (2004)

871  The inhibitory effect of retinoic acid on tumor growth is attenuated as tumors developed to more advanced stages, however, the mechanism of loss of anti-tumorigenic action of retinoic acid is not well understood. The purpose of this study was to investigate the anti-proliferative effect of all-trans retinoic acid (RA) during breast carcinogenesis using a novel cell culture system of human breast epithelial cells (HBEC). Type I normal HBEC with stem cell characteristics were developed from reduction mammoplasty tissues of healthy women. Immortalized (M13SV1), weakly tumorigenic (M13SV1R2), and highly tumorigenic (M13SV1R2N1) type I HBEC were derived sequentially from type I HBEC after expressing SV40 large T-antigen, irradiation with x-rays, and expressing the c-erbB2 (neu) oncogene. RA at 100 nM and 1 μM inhibited growth of immortalized and weakly tumorigenic HBEC, but not highly tumorigenic HBEC in 3 to 8 days. All cell lines tested expressed retinoic acid receptor-α (RARα), RARβ, and RARγ and RA had little effect on these RAR receptor protein levels. Immortalized and weakly tumorigenic cells showed low protein levels of p185c-erbB2/neu, while highly tumorigenic HBEC overexpressed p185c-erbB2/neu. RA had little effect on p185c-erbB2/neu protein expression and phosphorylation of JNK1/2 in all cell lines. Immortalized cells had higher phosphorylation of ERK1/2 than weakly and highly tumorigenic HBEC. RA inhibited phosphorylation of ERK1/2 only in immortalized cells, but not in weakly and highly tumorigenic HBEC. All cell lines showed similar protein levels of cyclin D1, while RA increased cyclin D1 level in highly tumorigenic HBEC. This is the first study investigating the effect of retinoic acid on different stages of breast carcinogenesis using immortalized, weakly tumorigenic, and highly tumorigenic HBEC sequentially derived from the same parental normal human breast stem cells. Our results indicate that loss of anti-proliferative effect of RA on highly tumorigenic HBEC might be associated with a stage of breast cells overexpressing neu oncogene. This overexpression of neu oncogene might interfere with the ability of RA to regulate cell signaling kinases and cell cycle regulating proteins. Further studies will explore how RA affects functionality of RAR isoforms, erbB2 activation and identify the genes differentially expressed by RA treatment. Research supported by NIH grant (CA79737) to DAT.
A photosensitizer-inhibitor conjugate for photodynamic therapy with simultaneous inhibition of treatment escape pathways
Authors: Ming Xiao, Jiangli Fan, Miao Li, Feng Xu, Xueze Zhao, Dongmei Xi, He Ma, Yueqing Li, Jianjun Du, Wen Sun, Xiaojun Peng
Journal: Biomaterials (2020)
National Hospital Quality Rankings
Authors: Jonathan A. Bae, Lesley H. Curtis, Adrian F. Hernandez
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
TIMP-1 induces an epithelial mesenchymal transition via upregulation of the transcription factor Twist in human breast epithelial cells
Authors: Rosemarie Chirco, Joshua Won, Rafael Fridman, Hyeong-Reh Kim
Journal: Cancer Research (2008)

5374  Turnover of the extracellular matrix (ECM) is regulated by the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs1-4). Previous in vitro and mouse studies demonstrated that TIMP-1 reduces tumor cell invasion through MMP inhibition. Therefore, it was unexpected to discover in clinical studies that TIMP-1 overexpression correlates with a poor prognosis in certain malignancies, including metastatic breast cancer. Importantly, we and others found that TIMP-1 is a potent inhibitor of apoptosis in a variety of cell types through either a MMP-dependent or -independent mechanism. Recently, we identified CD63, a member of the tetraspanin family of proteins, as a cell surface binding partner for TIMP-1 which modulates the integrin-mediated survival pathway in the human breast epithelial cell line MCF10A. In addition, we have made a novel finding that TIMP-1 expression in MCF10A cells induces phenotypic changes in cell morphology, cell-cell adhesion, and cytoskeletal remodeling taking on the hallmarks of an epithelial-mesenchymal transition (EMT). This is evidenced by loss of the epithelial cell adhesion molecules E-cadherin and beta-catenin and an increase in the mesenchymal markers vimentin, N-cadherin, and fibronectin. Treatment with rTIMP-1 also led to a loss of E-cadherin in MCF10A cells. Interestingly, TIMP-1 signaling induced Twist expression, a transcription factor known to suppress E-cadherin gene transcription and upregulate mesenchymal markers. SiRNA-mediated Twist knockdown restored E-cadherin expression in TIMP-1 overexpressing MCF10A cells, demonstrating a functional significance of Twist in TIMP-1 mediated EMT. We further demonstrated that TIMP-1 induces Twist expression and EMT in a CD63-dependent manner. Furthermore, analysis of TIMP-1 structural mutants unveiled that TIMP-1 interaction with CD63, activation of cell survival signaling, and induction of EMT in MCF10A cells does not require the MMP-inhibitory domain of TIMP-1. Taken together, we hypothesize that TIMP-1 binding to CD63 activates intracellular signal transduction pathways and leads to inhibition of apoptosis and induction of EMT in breast epithelial cells, facilitating breast cancer progression. Our study of the pleiotropic activities of TIMP-1 at the molecular level may enhance our understanding of TIMP-1’s multi-functions during tumor progression and metastasis. This information may also be useful in designing more rational, mechanism-based therapeutic interventions aimed at modulating activities of MMPs and TIMPs.
Abstract 11556: Depression is Associated With an Increased Risk of Rehospitalization in Patients With Heart Failure: A Systematic Review and Meta-analysis
Authors: Jakrin Kewcharoen, Chol Techorueangwiwat, Nattapat Nitinai, Sakditad Saowapa, Wasawat Vutthikraivit, Chanavuth Kanitsoraphan, Pattara Rattanawong
Journal: Circulation (2019)

Introduction: Heart failure (HF) is one of the world leading causes of hospitalization and rehospitalization. Several studies identified depression as a risk factor for rehospitalization in HF pati...
Early policy actions and emergency response to the COVID-19 pandemic in Mongolia: experiences and challenges
Authors: Ryenchindorj Erkhembayar, Emma Dickinson, Darmaa Badarch, Indermohan Narula, David Warburton, Graham Neil Thomas, Chimedsuren Ochir, Semira Manaseki-Holland
Journal: The Lancet Global Health (2020)

Country-led control measures to contain the spread of the novel coronavirus, COVID-19, have been diverse. Originating in Wuhan, China, in December, 2019, the COVID-19 outbreak was declared a pandemic by WHO on March 11, 2020. In recognition of the severity of the outbreak, and having the longest shared border with China, the Government of Mongolia activated the State Emergency Committee in January, 2020, on the basis of the 2017 Disaster Protection Law. As a result, various public health measures have been taken that led to delaying the first confirmed case of COVID-19 until March 10, 2020, and with no intensive care admissions or deaths until July 6, 2020. These measures included promoting universal personal protection and preventions, such as the use of face masks and handwashing, restricting international travel, suspending all training and educational activities from kindergartens to universities, and banning major public gatherings such as the celebration of the national New Year holiday. These measures have been accompanied by active infection surveillance and self-isolation recommendations. The Mongolian case shows that with robust preventive systems, an effective response to a pandemic can be mounted in a low-income or middle-income country. We hereby examine the emergency preparedness experience, effectiveness, and challenges of the early outbreak policies on COVID-19 prevention in Mongolia, as well as any unintended consequences.
Infrared spectral analysis of MCF-7 cells treated with serum-lipid extracts of Chinese origin segregates predominantly brominated flame retardant-exposed subjects from those with mainly organochlorine exposures
Authors: Francis Martin, Xinhui Bi, Michael Walsh, Xiaomin Wei, Pierre Martin-Hirsch, Guoying Sheng, Jiamo Fu, Gareth Thomas, Kevin Jones
Journal: Cancer Research (2007)

LB-304  Environmental exposures are implicated in the aetiology of several diseases. We set out to determine whether infrared (IR) spectra of treated MCF-7 cells derived using attenuated total reflection Fourier-transform IR (ATR) microspectroscopy could be used to signature exposures to different classes of environmental contaminant. Serum-lipid samples from residents living in an electronics waste (e-waste) dismantling region (Region E, n=26) in the south of P.R. China or from a nearby region (Region S, n=20) associated with the fishing industry were obtained. Following extraction, oestrogen receptor-positive MCF-7 cells were treated for 24 h with ≤5-mg lipid equivalent amounts of individual extracts; subsequently, IR spectra of treated-cell populations were obtained using ATR microspectroscopy. Levels of organochlorinated and brominated compounds in parallel extracts were determined. Principal component analysis (PCA) was employed to ascertain whether IR-spectral scores would cluster according to a particular cohort. Plotted clusters following PCA highlighted significant clustering depending on which set of extracts MCF-7 cells were treated with pointing to marked differences in the cell-biochemical modulating effects induced by either set of extracts. Analysis of contaminant profiles in the extracts showed that polybrominated diphenyl ethers (PBDEs) accounted for 46.0% of total organohalogens and were higher than dichloro-diphenyl-trichloroethanes (DDTs) in Region E while DDTs were the major contaminants (85.2% of total contaminant load), compared to PBDEs (8.7%) in Region S. These results suggest that ATR microspectroscopy can segregate cell-biochemical effects as a consequence of very different exposure paradigms.
Hand hygiene during COVID-19: Recommendations from the American Contact Dermatitis Society
Authors: Chandler W. Rundle, Colby L. Presley, Michelle Militello, Cara Barber, Douglas L. Powell, Sharon E. Jacob, Amber Reck Atwater, Kalman L. Watsky, Jiade Yu, Cory A. Dunnick
Journal: Journal of the American Academy of Dermatology (2020)

The recent COVID-19 pandemic has resulted in increased hand hygiene and hand cleansing awareness. To prevent virus transmission, the Centers for Disease Control and Prevention recommends frequent hand washing with soap and water. Hand hygiene products are available in a variety of forms, and while each of these formulations may be effective against COVID-19, they may also alter skin barrier integrity and function. As health care workers and the general population focus on stringent hand hygiene, the American Contact Dermatitis Society anticipates an increase in both irritant contact and allergic contact hand dermatitis. Alcohol-based hand sanitizers with moisturizers have the least sensitizing and irritancy potential when compared to soaps and synthetic detergents. This article provides an overview of the most frequently used hand hygiene products and their associations with contact dermatitis as well as recommendations from the American Contact Dermatitis Society on how to treat and prevent further dermatitis.
Uterine-Artery Embolization or Myomectomy for Uterine Fibroids
Authors: Isaac Manyonda, Anna-Maria Belli, Mary-Ann Lumsden, Jonathan Moss, William McKinnon, Lee J. Middleton, Versha Cheed, Olivia Wu, Fusun Sirkeci, Jane P. Daniels, Klim McPherson
Journal: New England Journal of Medicine (2020)

Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a reduced quality of life. For women who wish to preserve their uterus and who have not had a response to medical treatment, myomectomy and uterine-artery embolization are therapeutic options.
FRI0116 Hypermobility in sistemic lupus erythematosus
Authors: M Guma, A Olive, J Forcada, JC Duró, J Roca, S Holgado, E Casado, X Tena
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To investigate hypermobility in patients in systemic lupus erythematosus (SLE). <h3>Methods</h3> Setting: University Hospital; 80 patients with SLE (1999 ACR criteria), 90% females and 10% males, mean age 44 ± 16, who regularly attended a specialist SLE clinic were examined. Control group was composed of 280 patients attending a general practitioner office, 70% females and 30% males, mean age 46 ± 19. Joint laxity was measured according to Carter and Beighton criteria (total score 4 or more). A regression analysis was performed (SAS statistical package). <h3>Results</h3> Forty-eight% or patients with SLE and 12% of the control group were hypermobile. Regression analysis showed that after adjustment for the age and sex, patients with SLE were more hypermobile (Odds Ratio:5). Neither the clinical and analytical profile nor the use of corticosteroids was related to hipermobility. <h3>Conclusion</h3> Patients with SLE are more hypermobile that control group. No clinical or analytical profile is related. Steroids are not related to the presence of hypermobility in patients with SLE.