tbuckley/cabot-search huggingface dataset:
High-plex proteomic prognostic marker discovery for patients with pancreatic cancer adenocarcinoma using digital spatial profiling.
Authors: Nigel Balfour Jamieson, Assya Legrini, Holly Leslie, Stephan Dreyer, Andrew V Biankin, David Kuang-Fu Chang
Journal: Journal of Clinical Oncology (2022)

611 Background: The long-term outcomes following surgical resection for Pancreatic Ductal Adenocarcinoma (PDAC) remain poor, with only 20% of patients surviving 5 years after pancreatectomy. With its immune-privileged nature, starting from the early pre-neoplastic state, it appears to escape easily from the antitumor immune response. Despite rationale for targeting immune pathways in PDAC, there has been little benefit observed at this point. The aim of the current study was to interrogate immune landscape of PDAC utilising the Nanostring GeoMx Digital Spatial Profiler (DSP), a state-of-the art analysis platform enabling Hi-plex proteomic characterisation whilst maintaining tumor microenvironment (TME) topographical features. Methods: We assessed Formalin Fixed Paraffin Embedded (FFPE) tumor samples from 28 treatment-naive PDAC cases represented in a multi-regional tissue microarray (TMA) for which extensive IHC, molecular, genomic characterisation and clinicopathological follow-up data is available. Following multiplex IHC staining for DAPI, panCK, aSMA and CD3 to guide region selection, we employed the GeoMx DSP system (NanoString) to select regions within multiple TMA cores. We quantified 60 immune markers simultaneously in multiple tissue compartments defined by immunofluorescence co-localization including (tumor [panCK+ve], immune stroma (PanCK-ve]. Data analysis was performed by a combination of DSP analysis suite and custom R pipeline. Results: The spatially informed variable assessment by DSP was validated by both regression and variable prognostication compared with IHC for stromal CD3, CD8 CD68 in near serial TMA PDAC sections. Unsupervised analysis of DSP proteome data in the panCK-negative regions identified an immune poor group associated with shorter Overall Survival (OS) (13.0 versus 31.1months, P = 0.005). When transcriptomic subtype was considered, the checkpoint inhibitor B7-H3 was significantly upregulated in the squamous subtype tumours versus the classical group (Log2: 1.63, P = 0.001). Patients with high B7-H3 expression, using a median expression cut-off, were associated with shorter OS on multivariate analysis (Hazard Ratio: 4.16, P = 0.01) including lymph node and resection margin status, a finding that was validated in an external cohort at the transcriptome level. Conclusions: This pilot scale discovery study shows the potential of the Nanostring DSP technology in the identification of spatially-informed biomarkers with prognostic relevance in biopsy sized samples from treatment-naive PDAC. We identified a number of relevant candidate immune predictors in spatial context that are currently undergoing validation in larger independent cohorts and the neoadjuvant setting. Future studies will apply this technology to pre- and post-treatment biopsy samples.
Tom Nolan's research reviews—20 January 2022
Authors: Tom Nolan
Journal: BMJ (2022)

There's no place like home Older patients with acute illness are often on the borderline between needing admission and being able to manage at home.When talking through these options with them, we often cite the risk of adverse events from hospital admission (hospital acquired infections, pressure sores, deconditioning, and so on) as one good reason to stay at home.A cluster randomised controlled trial of a structured, ward based, improvement programme called "Eat Walk Engage" sought to reduce hospital acquired complications among older people. 1 No reduction in hospital associated complications was observed between patients on the four wards that received the intervention (aimed at improving nutrition, hydration, mobility, and cognitive and social engagement) and the four control wards.The overall rates of complications give a sense of how big a consideration this is for patients: of the over 65 year olds admitted to the study wards for at least three days, 49% suffered delirium, disability, incontinence, fall, or pressure injury associated with their hospitalisation.
<i>Erratum:</i> Vol. 70, No. 29
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In the report, "Heat-Related Emergency Department Visits During the Northwestern Heat Wave -United States, June 2021," on page 1020, the last sentence of the first paragraph should have read, "The record-breaking heat had the largest impact in Oregon and Washington, especially the Portland metropolitan area, with temperatures reaching 116°F (46.7°C), which is 42°F (23.3°C) hotter than the average daily maximum June temperature."
A planned system of patient education
Authors: P. G. Skillern
Journal: JAMA (1977)

A planned system of patient education is now used in more than 70 group clinics, hospitals, and other health care institutions. Essential features of this system are (1) a patient education center, (2) a patient educator, and (3) patient education programs. Structured programs are especially useful in the management of chronically ill patients. Patients have responded enthusiastically to this planned system. The response of physicians has ranged from enthusiastic to resistant. (<i>JAMA</i>238:878-879, 1977)
Progression of intimal thickening is greatest early after cardiac transplantation and not directly related to changes in vessel size (remodeling): A 4-year serial intravascular ultrasound study Hiroshi Tsutsui, Khaled M. Ziada, Paul Schoenhagen, Timothy D. Crowe, William A. Magyar, Atila Iyisoy, Jon Klingensmith, D. Geoffrey Vince, Gustavo Rincon, Steven E. Nissen, E. Murat Tuzcu. The Cleveland Clinic Foundation, Cleveland, OH
Journal: Journal of the American College of Cardiology (2001)
Diseases of the Ear, Nose, and Throat
Journal: JAMA (1949)

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
Abstract 172: Vascular Smooth Muscle Cell Activation is Regulated by miR-25 Induced miR-9 Suppression of Nox4 and Myocardin
Authors: Brandon M Schickling, Maysam Takapoo, Eric J Devor, Francis J Miller
Journal: Circulation Research (2017)

Vascular smooth muscle cell (SMC) de-differentiation with subsequent migration and proliferation into the subendothelial space is central to the progression of cardiovascular diseases. The Nox4 NADPH oxidase (Nox4) is implicated in maintaining the differentiated phenotype of SMC in part through myocardin, a master regulator of SMC gene expression. However, this process is poorly understood. We hypothesized that microRNAs (miR)-mediate changes in Nox4 expression and regulate SMC differentiation. Treatment of human SMCs with a miR-9 or miR-25 mimic silenced Nox4 mRNA through binding to the Nox4 3’UTR. However, only miR-25 was sufficient to downregulate Nox4 protein levels. We found that miR-25 induced the expression of miR-9 through a novel mechanism involving demethylation of the miR-9 promoter by Tet methylcytosine dioxygenase 2 (TET2). Inhibition of miR-9 induction by miR-25 with a miR-9 inhibitor restored Nox4 protein expression to basal levels. Furthermore, the miR-25-mediated decrease in Nox4 protein was ameliorated by inhibiting the proteasome with MG132. These data suggest a novel mechanism wherein miR-9 and miR-25 regulate Nox4 through both translational suppression and proteosomal degradation. Overexpression of miR-9 or miR-25 in human SMCs (1) suppressed myocardin mRNA and protein expression; (2) decreased expression of multiple SMC differentiation genes; and (3) was sufficient to induce cell migration. Thrombin and tumor necrosis factor increased the expression of miR-9 and miR-25 in human SMCs and inhibition of miR-9 prevented thrombin-mediated decrease in myocardin and SMC migration. Mir-9 and miR-25 levels were increased in SMCs derived from balloon injured rat aorta as compared to medial SMCs and in murine carotid artery ten days post carotid injury. A miR-9 inhibitor decreased neointimal formation by more than 50% in following partial carotid ligation in mice. These findings identify miR-9/Nox4 as a novel regulatory pathway of SMC differentiation and a potential therapeutic target in vascular disease.
Using synthetic chromosome controls to evaluate the sequencing of difficult regions within the human genome
Authors: Andre L. M. Reis, Ira W. Deveson, Bindu Swapna Madala, Ted Wong, Chris Barker, Joshua Xu, Niall Lennon, Weida Tong, Tim R. Mercer
Journal: Genome biology (2022)

Abstract Background Next-generation sequencing (NGS) can identify mutations in the human genome that cause disease and has been widely adopted in clinical diagnosis. However, the human genome contains many polymorphic, low-complexity, and repetitive regions that are difficult to sequence and analyze. Despite their difficulty, these regions include many clinically important sequences that can inform the treatment of human diseases and improve the diagnostic yield of NGS. Results To evaluate the accuracy by which these difficult regions are analyzed with NGS, we built an in silico decoy chromosome, along with corresponding synthetic DNA reference controls, that encode difficult and clinically important human genome regions, including repeats, microsatellites, HLA genes, and immune receptors. These controls provide a known ground-truth reference against which to measure the performance of diverse sequencing technologies, reagents, and bioinformatic tools. Using this approach, we provide a comprehensive evaluation of short- and long-read sequencing instruments, library preparation methods, and software tools and identify the errors and systematic bias that confound our resolution of these remaining difficult regions. Conclusions This study provides an analytical validation of diagnosis using NGS in difficult regions of the human genome and highlights the challenges that remain to resolve these difficult regions.
Principal component analysis of the T wave as an index of life-threatening arrhythmia risk Thomas Hilbel, Eva vom Brocke, Marc Reiter, Patricia Kraft, Jutta Ruf-Richter, Johannes Brachmann. University of Heidelberg, Department of Cardiology, Heidelberg, Germany, Klinikum Coburg, Coburg, Germany
Journal: Journal of the American College of Cardiology (2001)
SARS-CoV-2 outbreaks in hospitals and long-term care facilities in Germany: a national observational study
Authors: Beneditta Suwono, Annika Steffen, Birgitta Schweickert, Viktoria Schönfeld, Michael Brandl, Mirco Sandfort, Niklas Willrich, Tim Eckmanns, Sebastian Haller
Journal: The Lancet Regional Health - Europe (2022)

Outbreaks of coronavirus disease (COVID-19) in hospitals and long-term care facilities (LTCFs) pose serious public health threats. We analysed how frequency and size of SARS-CoV-2 outbreaks in hospitals and LTCFs have altered since the beginning of the pandemic, in particular since the start of the vaccination campaign.We used mandatory notification data on SARS-CoV-2 cases in Germany and stratified by outbreak cases in hospitals and LTCFs. German vaccination coverage data were analysed. We studied the association of the occurrence of SARS-CoV-2 outbreaks and outbreak cases with SARS-CoV-2 cases in Germany throughout the four pandemic waves. We built also counterfactual scenarios with the first pandemic wave as the baseline.By 21 September 2021, there were 4,147,387 SARS-CoV-2 notified cases since March 2020. About 20% of these cases were reported as being related to an outbreak, with 1% of the cases in hospitals and 4% in LTCFs. The median number of outbreak cases in the different phases was smaller (≤5) in hospitals than in LTCFs (>10). In the first and second pandemic waves, we observed strong associations in both facility types between SARS-CoV-2 outbreak cases and total number of notified SARS-CoV-2 cases. However, during the third pandemic wave we observed a decline in outbreak cases in both facility types and only a weak association between outbreak cases and all cases.The vaccination campaign and non-pharmaceutical interventions have been able to protect vulnerable risk groups in hospitals and LTCFs.No specific funding.
Laponite‐Based Nanomaterials for Drug Delivery
Authors: Gita Kiaee, Nikolaos Dimitrakakis, Shabnam Sharifzadeh, Han‐Jun Kim, Reginald K. Avery, Kamyar Mollozadeh Moghaddam, Reihaneh Haghniaz, Ezgi Pinar Yalcintas, Natan Roberto de Barros, Solmaz Karamikamkar, Alberto Libanori, Ali Khademhosseini, Parastoo Khoshakhlagh
Journal: Advanced Healthcare Materials (2022)

Abstract Laponite is a clay‐based material composed of synthetic disk‐shaped crystalline nanoparticles with highly ionic, large surface area. These characteristics enable the intercalation and dissolution of biomolecules in Laponite‐based drug delivery systems. Furthermore, Laponite's innate physicochemical properties and architecture enable the development of tunable pH‐responsive drug delivery systems. Laponite's coagulation capacity and cation exchangeability determine its exchange capabilities, drug encapsulation efficiency, and release profile. These parameters are exploited to design highly controlled and efficacious drug delivery platforms for sustained drug release. In this review, they provide an overview of how to design efficient delivery of therapeutics by leveraging the properties and specific interactions of various Laponite–polymer composites and drug moieties.
Gene-Level Germline Contributions to Clinical Risk of Recurrence Scores in Black and White Patients with Breast Cancer
Authors: Achal Patel, Montserrat García-Closas, Andrew F. Olshan, Charles M. Perou, Melissa A. Troester, Michael I. Love, Arjun Bhattacharya
Journal: Cancer Research (2021)

Abstract Continuous risk of recurrence scores (CRS) based on tumor gene expression are vital prognostic tools for breast cancer. Studies have shown that Black women (BW) have higher CRS than White women (WW). Although systemic injustices contribute substantially to breast cancer disparities, evidence of biological and germline contributions is emerging. In this study, we investigated germline genetic associations with CRS and CRS disparity using approaches modeled after transcriptome-wide association studies (TWAS). In the Carolina Breast Cancer Study, using race-specific predictive models of tumor expression from germline genetics, we performed race-stratified (N = 1,043 WW, 1,083 BW) linear regressions of three CRS (ROR-S: PAM50 subtype score; proliferation score; ROR-P: ROR-S plus proliferation score) on imputed tumor genetically regulated tumor expression (GReX). Bayesian multivariate regression and adaptive shrinkage tested GReX-prioritized genes for associations with tumor PAM50 expression and subtype to elucidate patterns of germline regulation underlying GReX-CRS associations. At FDR-adjusted P &amp;lt; 0.10, 7 and 1 GReX prioritized genes among WW and BW, respectively. Among WW, CRS were positively associated with MCM10, FAM64A, CCNB2, and MMP1 GReX and negatively associated with VAV3, PCSK6, and GNG11 GReX. Among BW, higher MMP1 GReX predicted lower proliferation score and ROR-P. GReX-prioritized gene and PAM50 tumor expression associations highlighted potential mechanisms for GReX-prioritized gene to CRS associations. Among patients with breast cancer, differential germline associations with CRS were found by race, underscoring the need for larger, diverse datasets in molecular studies of breast cancer. These findings also suggest possible germline trans-regulation of PAM50 tumor expression, with potential implications for CRS interpretation in clinical settings. Significance: This study identifies race-specific genetic associations with breast cancer risk of recurrence scores and suggests mediation of these associations by PAM50 subtype and expression, with implications for clinical interpretation of these scores.
Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis
Authors: Ting Dai, Wenming He, Shuangshuang Tu, Jinru Han, Bo Yuan, Chenyang Yao, Wenzhi Ren, Aiguo Wu
Journal: Bioactive Materials (2022)

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.
Transient left ventricular cavity dilatation during stress echocardiography is a strong predictor of cardiovascular mortality Binoy K. Singh, J. Mahenthiran, Varinder P. Singh, Madhu Jyothinagaram, Manish Undavia, Siu-Sun Yao, Farooq A. Chaudry. Columbia University St. Luke's Roosevelt Hospital Center, New york, NY
Journal: Journal of the American College of Cardiology (2001)
GW25-e0160 A New Strategy for Pericardiocentesis with a Visual Puncture System: A Feasibility and Efficiency Study in a Pericardial Effusion Model
Authors: Yanmei Feng, Xun Liu, Gang Xu, Yong Zhang, Jun Qian, Ziyang Huang, Bingbing Yan, Yijun Liu, Huisheng Deng, Rui Guo
Journal: Journal of the American College of Cardiology (2014)
Suppressor cells may help prevent fetal rejection
Authors: W. Check
Journal: JAMA (1978)

Since the discovery early in this century that the body's immune system is capable of initiating the rejection of foreign cells, there has been continuing speculation about why the fetus is exempt from this reaction. Suggestions that the placenta prevents passage of antigenic material between the mother and fetus have been disproved, and it is now known that fetal and maternal cells are exchanged through the placenta and that both humoral and cellular immunity to fetal antigens develop in the mother. Recently, in an attempt to find out whether the normal immunity of such women might be in some way blocked, J. B. Dossetor, MD, PhD, professor of medicine and director of the transplant research laboratory, and T. Kovithavongs, MD, assistant professor of medicine, both of the University of Alberta in Edmonton, looked for the presence of suppressor cells in the blood of multiparous women. They found that multiparous women
Outcomes of Methotrexate-Associated T-Cell and NK/T-Cell Lymphoproliferative Disorders in Patients with a History of Rheumatological Disorders: A Retrospective Analysis of EBV-Association and Response to MTX Withdrawal
Authors: William T Johnson, Danielle Garfunkel, Misung Yi, Benjamin E Leiby, Saritha Kartan, Pierluigi Porcu
Journal: Blood (2018)
Research brief
Authors: Dara Mohammadi
Journal: The Lancet Infectious Diseases (2017)

Women with previous herpes simplex virus type-1 (HSV-1) infection have persistent antibodies against the virus and can pass protection to their unborn babies. In laboratory studies using autopsied human tissue, the researchers showed that the antibodies remain in the trigeminal ganglion (a key site of HSV infection) in mothers and that they travel to the same site in their fetus. In studies in mice, they showed that these vertically transmitted antibodies completely protect newborn mice from infection.
Klinische Wochenschrift, Berlin
Journal: JAMA (1964)

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
Otorhinolaryngology
Authors: Bobby R. Alford
Journal: JAMA (1978)

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