tbuckley/cabot-search huggingface dataset:
Considering Surgeon Skill in Randomized Clinical Trials
Authors: Amir A. Ghaferi, Justin B. Dimick
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Control of heme metabolism with synthetic metalloporphyrins.
Authors: A Kappas, G S Drummond
Journal: Journal of Clinical Investigation (1986)

Studies with synthetic metal-porphyrin complexes in which the central iron atom of heme is replaced by other elements indicate that those heme analogues that cannot be enzymatically degraded to bile pigments possess novel biological properties that may have considerable clinical as well as experimental value. Such studies have revealed the important role that the central metal atom plays in determining the physiological and pharmacological properties of metal-porphyrin complexes; and they have demonstrated that the form in which animals and humans are exposed to trace metals, i.e., inorganic, organified, porphyrin-chelated, etc., can be of great importance in determining the biological responses that such elements elicit, especially with respect to actions on heme synthesis and degradation and cytochrome P-450 formation and function. Study of the biological properties of synthetic metalloporphyrins represents a potentially fruitful area of research and the results may have significant value for basic as well as clinical disciplines.
Enabling an Open Data Ecosystem for the Neurosciences
Authors: Martin Wiener, Friedrich T. Sommer, Zachary G. Ives, Russell A. Poldrack, Brian Litt
Journal: Neuron (2016)

(Neuron 92, 617–621; November 2, 2016) In the original article, the reference provided for BIDS (Gorgolewski et al., 2016) was incorrect. The article has now been corrected online with the appropriate reference. The authors apologize for the error. Enabling an Open Data Ecosystem for the NeurosciencesWiener et al.NeuronNovember 02, 2016In BriefWiener et al. discuss the problems and complexities of neuroscience data sharing, including the challenges of incentives, discoverability, and sustainability, and suggest potential future solutions to help cultivate an ecosystem of data sharing. Full-Text PDF Open Archive
Abstract 166: Matrix Metalloproteinase-9 Mediates Post-hypoxic Vascular Pruning Of Cerebral Blood Vessels By Degrading Laminin And Claudin-5
Authors: Amin Boroujerdi, Jennifer V Welser-Alves, Richard Milner
Journal: Circulation Research (2014)

Objective: Vascular remodeling involves a highly coordinated break-down and build-up of the vascular basal lamina and inter-endothelial tight junction proteins. The goal of this study was to examine the role of matrix metalloproteinase-9 (MMP-9) in remodeling of cerebral blood vessels, both in hypoxia-induced angiogenesis and in the vascular pruning that accompanies the switch from hypoxia back to normoxia. Approach and Results: In a chronic mild hypoxia model of cerebrovascular remodeling, gel zymography revealed that MMP-9 levels were increased, both in the hypoxic angiogenic response and in the post-hypoxic pruning response. Compared to wild-type mice, MMP-9 KO mice showed no alteration in hypoxic-induced angiogenesis, but did show marked delay in post-hypoxic vascular pruning. In wild-type mice, vascular pruning was associated with fragmentation of vascular laminin and the tight junction protein claudin-5, while this process was markedly attenuated in MMP-9 KO mice. In vitro experiments showed that hypoxia stimulated MMP-9 expression in brain endothelial cells (BECs) but not pericytes. While immunofluorescent and flow cytometry analyses showed that hypoxia led to reduced expression of laminin and claudin-5 in wild-type BECs, this decrease was absent in MMP-9 KO BECs. Conclusions: These results show that while MMP-9 is not essential for hypoxic-induced cerebral angiogenesis, it plays an important role in post-hypoxic vascular pruning by degrading laminin and claudin-5. Our data support the concept that MMP-9 inhibition might provide therapeutic benefit in the treatment of ischemic stroke, by preventing post-hypoxic vascular pruning, thereby optimizing vascular density and integrity.
Abstract 4759: HOXB7 functions as a co-activator of estrogen receptor in the development of tamoxifen resistance.
Authors: Kideok Jin, Wei Wen Teo, Takahiro Yoshida, Sunju Park, Saraswati Sukumar
Journal: Cancer Research (2013)

Abstract Background: Multiple factors including long term treatment with tamoxifen are involved in the development of selective estrogen receptor modulator (SERM)-resistance in ERα positive breast cancer. Increased expression of HER family members can also directly alter cellular responses to tamoxifen, but the mechanism underlying the increased expression of the HERs is not clear. In this report we show that HOXB7 is an upstream regulator of HER2 and ER expression. Results: Overexpression of HOXB7 results in upregulation of HER2 and ERα target genes, while knockdown of HOXB7 with siRNA in tamoxifen-resistant cell lines causes decrease of HER2 and ERα target genes expression and loss of tamoxifen resistance. To mediate upregulation of HER2 and ER-target genes occurring in tamoxifen resistance, the HOXB7-ERα complex recruits ERα coactivators and promotes HER2- and ER-target genes transcriptional activity through direct binding to the HER2 enhancer and regulatory regions of ER target genes. However, depletion of HOXB7 negatively affects the binding affinity of its cofactors to the HER2 enhancer element and ER-binding sites. Also, it is likely that miR196a controls HOXB7 expression; reducing miR196a levels in tamoxifen-resistant cells causes an increase of HOXB7 expression. Overexpression of miR196a sensitizes MCF-7 tamoxifen resistant cells to tamoxifen through downregulation of HER2 and ER-target genes while inhibition of miR196a by anti-miR196a inhibitors increases tamoxifen resistance through the upregulation of HER and ER target genes in MCF-7 cells. Further, miRNA 196a is regulated by c-MYC which undergoes stabilization through the EGFR-HER2 signaling pathway. Depletion of c-MYC by MYC shRNA enhances tamoxifen sensitivity by increasing the level of miR196a transcripts. Also, by c-MYC ChIP assay, we found that c-MYC inhibits miR196a expression through direct binding to its promoter region. Conclusions: Overexpression of HOXB7 is a key event in the initiation and maintenance of tamoxifen resistance. These studies suggest that HOXB7 acts as a key regulator orchestrating two major groups of target molecules, ERα and HER2, in the oncogene hierarchy. Blocking MYC expression or reexpression of miR196a in TAM-R cells may provide novel strategies for reversing SERM-resistance. Therefore, we have provided additional evidence that supports the thesis that functional antagonism of HOXB7 has the potential to circumvent tamoxifen resistance. Citation Format: Kideok Jin, Wei Wen Teo, Takahiro Yoshida, Sunju Park, Saraswati Sukumar. HOXB7 functions as a co-activator of estrogen receptor in the development of tamoxifen resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4759. doi:10.1158/1538-7445.AM2013-4759
Periodontal disease and adverse pregnancy outcomes
Authors: Yiorgos A. Bobetsis, Filippo Graziani, Mervi Gürsoy, Phoebus N. Madianos
Journal: Periodontology 2000 (2020)

Abstract Periodontal diseases are considered not only to affect tooth‐supporting tissues but also to have a cause‐and‐effect relationship with various systemic diseases and conditions, such as adverse pregnancy outcomes. Mechanistic studies provide strong evidence that periodontal pathogens can translocate from infected periodontium to the feto‐placental unit and initiate a metastatic infection. However, the extent and mechanisms by which metastatic inflammation and injury contribute to adverse pregnancy outcomes still remain unclear. The presence of oral bacteria in the placenta of women with term gestation further complicates our understanding of the biology behind the role of periodontal pathogens in pregnancy outcomes. Epidemiological studies demonstrate many methodological inconsistencies and flaws that render comparisons difficult and conclusions insecure. Therefore, despite the fact that a number of prospective studies show a positive association between periodontal diseases and various adverse pregnancy outcomes, the evidence behind it is still weak. Future well‐designed explanatory studies are necessary to verify this relationship and, if present, determine its magnitude. The majority of high‐quality randomized controlled trials reveal that nonsurgical periodontal therapy during the second trimester of gestation does not improve pregnancy outcomes. From a biological standpoint, this can be partially explained by the fact that therapy rendered at the fourth to sixth months of pregnancy is too late to prevent placental colonization by periodontal pathogens and consequently incapable of affecting pathogen‐induced injury at the feto‐placental unit. Thus, interventions during the preconception period may be more meaningful. With the increase in our understanding on the potential association between periodontal disease and adverse pregnancy outcomes, it is clear that dental practitioners should provide periodontal treatment to pregnant women that is safe for both the mother and the unborn child. Although there is not enough evidence that the anti‐infective therapy alters pregnancy outcomes, it improves health‐promoting behavior and periodontal condition, which in turn advance general health and risk factor control.
Prenatal alcohol exposure and childhood atopic disease: A Mendelian randomisation approach
Authors: Seif Shaheen, Clare Rutterford, Luisa Zuccolo, Susan Ring, George Davey Smith, John Henderson
Journal: European Respiratory Journal (2012)

Background:  Few epidemiological studies have investigated whether alcohol consumption during pregnancy increases the risk of childhood atopic disease. A difficulty with using reported alcohol intake to measure exposure is that under-reporting is common and associations are likely to be confounded. In contrast, a Mendelian randomisation approach should produce unbiased and unconfounded effect estimates and can strengthen causal inference.   Methods:  In a UK population based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), we have analysed whether the maternal alcohol dehydrogenase (ADH)1B gene variant is associated with childhood atopic outcomes at 7 years of age. Carriers of the minor A allele drink less in pregnancy and metabolise alcohol faster, thus reducing adverse effects of alcohol on the fetus. We also analysed associations with reported alcohol consumption in pregnancy.   Results:  Maternal ADH1B genotype was strongly associated with childhood asthma. Mothers carrying the minor A allele were half as likely to have children with asthma as mothers who were homozygous for the G allele (odds ratio 0.50 (95% CI: 0.33 to 0.75), P=0.001, N=6,701). There were no significant associations with other atopic outcomes. In contrast, mothers who reported drinking once a week or more in the last two months of pregnancy were less likely to have children with asthma and hayfever than mothers who reported never drinking (OR 0.81 (0.65 to 0.99) and 0.75 (0.59 to 0.95), respectively).   Conclusions:  The genetic results suggest that prenatal alcohol exposure increases the risk of childhood asthma. The contradictory associations with reported alcohol intake are likely to be confounded.
Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis
Authors: Yu Yang, Wensheng Li, Hailan Zhu, Xiong-Fei Pan, Yunzhao Hu, Clare Arnott, Weiyi Mai, Xiaoyan Cai, Yuli Huang
Journal: BMJ (2020)

To evaluate the prognosis of unrecognised myocardial infarction determined by electrocardiography (UMI-ECG) or cardiac magnetic resonance imaging (UMI-CMR).Systematic review and meta-analysis of prospective studies.Electronic databases, including PubMed, Embase, and Google Scholar.Prospective cohort studies were included if they reported adjusted relative risks, odds ratios, or hazard ratios and 95% confidence intervals for all cause mortality or cardiovascular outcomes in participants with unrecognised myocardial infarction compared with those without myocardial infarction.The primary outcomes were composite major adverse cardiac events, all cause mortality, and cardiovascular mortality associated with UMI-ECG and UMI-CMR. The secondary outcomes were the risks of recurrent coronary heart disease or myocardial infarction, stroke, heart failure, and atrial fibrillation. Pooled hazard ratios and 95% confidence intervals were reported. The heterogeneity of outcomes was compared in clinically recognised and unrecognised myocardial infarction.The meta-analysis included 30 studies with 253 425 participants and 1 621 920 person years of follow-up. UMI-ECG was associated with increased risks of all cause mortality (hazard ratio 1.50, 95% confidence interval 1.30 to 1.73), cardiovascular mortality (2.33, 1.66 to 3.27), and major adverse cardiac events (1.61, 1.38 to 1.89) compared with the absence of myocardial infarction. UMI-CMR was also associated with increased risks of all cause mortality (3.21, 1.43 to 7.23), cardiovascular mortality (10.79, 4.09 to 28.42), and major adverse cardiac events (3.23, 2.10 to 4.95). No major heterogeneity was observed for any primary outcomes between recognised myocardial infarction and UMI-ECG or UMI-CMR. The absolute risk differences were 7.50 (95% confidence interval 4.50 to 10.95) per 1000 person years for all cause mortality, 11.04 (5.48 to 18.84) for cardiovascular mortality, and 27.45 (17.1 to 40.05) for major adverse cardiac events in participants with UMI-ECG compared with those without myocardial infarction. The corresponding data for UMI-CMR were 32.49 (6.32 to 91.58), 37.2 (11.7 to 104.20), and 51.96 (25.63 to 92.04), respectively.UMI-ECG or UMI-CMR is associated with an adverse long term prognosis similar to that of recognised myocardial infarction. Screening for unrecognised myocardial infarction could be useful for risk stratification among patients with a high risk of cardiovascular disease.
Role of the Mammalian Target of Rapamycin Pathway in Liver Cancer: From Molecular Genetics to Targeted Therapies
Authors: Xinjun Lu, Panagiotis Paliogiannis, Diego F. Calvisi, Xin Chen
Journal: Hepatology (2020)

Primary liver cancers, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), are highly lethal tumors, with high worldwide frequency and few effective treatment options. The mammalian target of rapamycin (mTOR) complex is a central regulator of cell growth and metabolism that integrates inputs from amino acids, nutrients, and extracellular signals. The mTOR protein is incorporated into two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Specifically, mTORC1 regulates protein synthesis, glucose and lipid metabolism, and autophagy, whereas mTORC2 promotes liver tumorigenesis through modulating the adenine/cytosine/guanine family of serine/threonine kinases, especially the protein kinase B proteins. In human HCC and iCCA samples, genomics analyses have revealed the frequent deregulation of the mTOR complexes. Both in vitro and in vivo studies have demonstrated the key role of mTORC1 and mTORC2 in liver‐tumor development and progression. The first‐generation mTOR inhibitors have been evaluated for effectiveness in liver‐tumor treatment and have provided unsatisfactory results. Current research efforts are devoted to generating more efficacious mTOR inhibitors and identifying biomarkers for patient selection as well as for combination therapies. Here, we provide a comprehensive review of the mechanisms leading to a deregulated mTOR signaling cascade in liver cancers, the mechanisms whereby the mTOR pathway contributes to HCC and iCCA molecular pathogenesis, the therapeutic strategies, and the challenges to effectively inhibit mTOR in liver‐cancer treatment. Conclusion : Deregulated mTOR signaling significantly contributes to HCC and iCCA molecular pathogenesis. mTOR inhibitors, presumably administered in association with other drugs, might be effective against subsets of human liver tumors.
Low penetrance breast cancer predisposition SNPs are site specific.
Authors: NM Mc Inerney, G Colleran, A Walther, A Rowan, S Spain, AM Jones, S Tuohy, E Barclay, C Curran, N Miller, MJ Kerin, I Tomlinson, S Eli
Journal: Cancer Research (2009)

Abstract Abstract #6085 Introduction&amp;#x2028; A locus on chromosome 8q24.21 has been shown to harbours variants that predispose to breast cancer, colorectal cancer and prostate cancer. The finding of risk variants clustering at 8q24 suggests that there may be common molecular mechanisms that predispose to the common epithelial cancers. The aim of this study was to determine whether the colorectal and prostate susceptibility alleles on 8q24 and other recently identified colorectal and prostate susceptibility alleles elsewhere in the genome are also associated with breast cancer risk.&amp;#x2028; Methods&amp;#x2028; In this study, we have studied three SNPs on 8q24.21: the breast cancer susceptibility SNP, rs13281615; the colorectal/prostate cancer susceptibility SNP, rs6983267; and the prostate susceptibility SNP, rs16901979; and eleven other SNPs outside of this region that have recently been shown to predispose to either prostate or colorectal cancer. Each SNP was genotyped in 988 sporadic breast cancer cases and 1016 controls from the West of Ireland using KASPar genotyping technology. We combined our data with publicly available datasets (breast: CGEMS, Fletcher et al.; prostate: CGEMS, Eeles et al.; CRC: Tomlinson et al.) by allelic, genotypic, dominant and recessive models using standard techniques of meta-analysis for SNPs previously identified to confer an increased cancer risk in specific tissue types. All analyses were done in Stata 9.2 (Stata Corp, TX).&amp;#x2028; Results&amp;#x2028; rs13281615 was associated with breast cancer (Pallelic test= 1.8 -2) with an odds ratio of 1.17. However there was no association between any of the prostate or colorectal susceptibility SNPs at 8q24 or elsewhere with breast cancer risk in our cohort. The data support the existence of a low-penetrance susceptibility locus for breast cancer near rs13281615; this locus seems to be distinct from the prostate and colorectal cancer loci in that region, even if the functional effects of the predisposition loci affect the same target gene or protein. Meta-analysis did not show an association between reported cancer SNPs and cancers in other tissue types.&amp;#x2028; Conclusions&amp;#x2028; This study suggests that low penetrance susceptibility SNPs for breast, colorectal and prostate cancer are distinct and argues against the presence of ''general' cancer predisposition SNPs. Although 8q24 harbours variants that predispose to all three cancers the susceptibility loci within the region appear to be specific for the different cancer types. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6085.
Considering the Effect of Combining α-Blockers With Bladder Antimuscarinics in Treatment of Overactive Bladder Symptoms
Authors: Gulistan Bahat, Senay Gunaydin, Mehmet Akif Karan
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis
Authors: Wael El-Matary, Stephen L. Guthery, Achiya Z. Amir, Matthew DiGuglielmo, Laura G. Draijer, Katryn N. Furuya, Nitika Gupta, Jessica T. Hochberg, Simon Horslen, Nanda Kerkar, Bart G.P. Koot, Trevor J. Laborda, Kathleen M. Loomes, Cara Mack, Mercedes Martinez, Alexander Miethke, Tamir Miloh, Douglas Mogul, Saeed Mohammed, Stacy Moroz, Nadia Ovchinsky, Emily R. Perito, Girish Rao, Amanda Ricciuto, Pushpa Sathya, Kathleen B. Schwarz, Uzma Shah, Ruchi Singh, Nisreen Soufi, Pamela L. Valentino, Andréanne Zizzo, Mark R. Deneau
Journal: Clinical Gastroenterology and Hepatology (2020)