tbuckley/cabot-search huggingface dataset:
Abstract 19409: Noninvasive Peripheral Vascular Resistance Measured by a Polyvinylidene Fluoride Sensor Identifies Patterns of Oxygen Debt Repayment During Resuscitation After Hemorrhage
Authors: Sardar Ansari, Mohamad Hakam Tiba, Kenn Oldham, Kevin R Ward, Kayvan Najarian
Journal: Circulation (2016)

Introduction:  Oxygen debt (O 2 D) is one of the main indicators for organ failure as a result of hemorrhage (Hem) and its repayment rate (RR) is critical during resuscitation (Res). Peripheral vascular resistance (PVR) during Res may have a significant impact on the reperfusion of the ischemic tissue and repayment of O 2 D. We have used a novel portable Polyvinylidene Fluoride (PVDF) based sensor in the form of a ring to estimate PVR and to examine the O 2 D-RR.   Hypothesis:  Early PVR post-Res is correlated with O 2 D-RR and can be measured using the PVDF ring.   Methods:  Seven pigs underwent controlled Hem with a target O 2 D of 80 mL/kg and resuscitated with whole shed blood to restore their hemodynamic parameters. The PVDF sensor was placed on the distal forelimb and was used to estimate PVR based on a mechanical model that uses the pulse pressure obtained from blood pressure (BP) and the amount of artery expansion. It was normalized by the PVR at the end of Res or when the systolic-BP peaks, whichever took place first, to find the relative PVR (R-PVR).   Results:  The relative O 2 D-RR, defined as O 2 D-RR/(O 2 D + C) where C=50 mL/kg is a constant value avoiding inflation of the ratio for small O 2 D values, and R-PVR were measured and averaged every five minutes post-Res until O 2 D was fully repaid (figure). The O 2 D was repaid within 2 hours for all animals except one (shown in red) which had distinctly higher values of R-PVR. Moreover, three animals repaid their O 2 D in less than one hour while the others took longer. These two groups were separated by the average R-PVR values (log-transformed) in the first five minutes post-Res (p=0.028).   Conclusion:  The PVDF sensor can be used to estimate the PVR and may be capable of providing information helpful in guiding Res. The reduction in the PVR may indicate adequacy of administered fluid, resulting in the return of the vascular tone and improved perfusion of ischemic tissues, which might lead to quicker O 2 D repayment, recovery and reduced chance of organ failure.
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans
Authors: Khadijah A. Mitchell, Adriana Zingone, Leila Toulabi, Jacob Boeckelman, Bríd M. Ryan
Journal: Clinical Cancer Research (2017)

Abstract Purpose: To determine whether racial differences in gene and miRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AAs) and European Americans (EAs). Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (∼40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA (n = 22 AAs and 19 EAs) and miRNA (n = 42 AAs and 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AAs and EAs. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and miRNA target enrichment were assessed. Results: AA-enriched differential gene expression was characterized by stem cell and invasion pathways. Differential gene expression in lung tumors from EAs was primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration were observed in AAs (P &amp;lt; 0.05); however, PD-L1, PD-L2 expression was similar between both. Conclusions: Comparative transcriptomic profiling revealed clear differences in lung tumor biology between AAs and EAs. Increased participation by AAs in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AAs and EAs. Clin Cancer Res; 23(23); 7412–25. ©2017 AACR.
Behavior-Dependent Activity and Synaptic Organization of Septo-hippocampal GABAergic Neurons Selectively Targeting the Hippocampal CA3 Area
Authors: Abhilasha Joshi, Minas Salib, Tim James Viney, David Dupret, Peter Somogyi
Journal: Neuron (2017)

Rhythmic medial septal (MS) GABAergic input coordinates cortical theta oscillations. However, the rules of innervation of cortical cells and regions by diverse septal neurons are unknown. We report a specialized population of septal GABAergic neurons, the Teevra cells, selectively innervating the hippocampal CA3 area bypassing CA1, CA2, and the dentate gyrus. Parvalbumin-immunopositive Teevra cells show the highest rhythmicity among MS neurons and fire with short burst duration (median, 38 ms) preferentially at the trough of both CA1 theta and slow irregular oscillations, coincident with highest hippocampal excitability. Teevra cells synaptically target GABAergic axo-axonic and some CCK interneurons in restricted septo-temporal CA3 segments. The rhythmicity of their firing decreases from septal to temporal termination of individual axons. We hypothesize that Teevra neurons coordinate oscillatory activity across the septo-temporal axis, phasing the firing of specific CA3 interneurons, thereby contributing to the selection of pyramidal cell assemblies at the theta trough via disinhibition.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhYzZmMDNkMmNkMzZkYjA1YjFiYWQ0Nzg3OTA2YmFmMSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4NDE1OTM2fQ.AEnFPXhskV8ykc7A_gZCqgKfBTmL3Zh9DdXaMos65XbL0_OT1nzFKxic3Mfoi36dh-YXfxyknSDLhl6DoQNUudfPO3iPCqPpQIRHTzbVjw_2AbwLJ9t7HOHNCqeIxKEIlrxeOUzBkjZKsygm12vhMO9prhHU5ycs0AJXwJUY1SuaRw-PeG_aJu70GqkBvtlpiKsVhwhANvdqYeXF8tzV-EJyUU1Zwic2mtxcCWP7w3sGDCmrYniqT5-OEkTnrhAdi0tXry2UFjKVP4sDyEg612n9t10GbrEJ1EJpOeWw5_0H9mgYzry2iViM9OfqAEd3WcKBUIFGlPgGtdKgXGs5eg(mp4, (57.91 MB) Download video
A Solution-Focused Research Approach to Achieve an Implementable Revolution in Digital Mental Health
Authors: David C. Mohr, Heleen Riper, Stephen M. Schueller
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
HIV epidemic among men who have sex with men in the Czech Republic, 2016: high time for targeted action
Authors: Viktor Mravčík, Michal Pitoňák, Robert Hejzák, Barbara Janíková, Ivo Procházka
Journal: Eurosurveillance (2017)

Reported incidence of human immunodeficiency virus (HIV) infection in the Czech Republic increased steeply over the past decade from 90 new cases in 2005 to 266 in 2015. This increase is almost exclusively attributed to sexual transmissions between men who have sex with men (MSM). In 2015, there were 79% (n=210) newly diagnosed cases among MSM, 17% (n=45) were attributed to heterosexual transmission and 1% (n=3) to people who inject drugs. Interventions targeted at MSM have not yet been prioritised in the broadly focused national HIV prevention strategy which this is envisaged to change in the programme set out for 2018 to 2022. The national budget for HIV prevention has been reduced, however, and this remains. Availability of voluntary counselling and testing has decreased substantially in the past decade. Post- and pre-exposure prophylaxis for sexual intercourse among MSM are not part of the HIV prevention policy and the concept of treatment as prevention is not fully recognised. Provision of a combined prevention strategy with a focus on MSM, reflecting the above factors including stigmatisation, should contribute to reverse the development of a concentrated HIV epidemic among MSM in the Czech Republic.
STUDIES ON ANTIBODY PRODUCTION
Authors: Thomas F. O'Brien, Albert H. Coons
Journal: The Journal of Experimental Medicine (1963)

Incorporation of 5-bromodeoxyuridine (BUDR) in the culture medium for the 2nd, 3rd, or 4th day after in vitro antigen stimulation of rabbit popliteal lymph node fragments suppressed the in vitro anamnestic antibody response described previously. Before or after this 3-day period, BUDR had no measurable effect. The results suggest that the antibody response in this in vitro system depends upon cell multiplication during this period.
The short‐term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct‐acting antivirals: An ERCHIVES study
Authors: Darrick K. Li, Yanjie Ren, Daniel S. Fierer, Stephanie Rutledge, Obaid S. Shaikh, Vincent Lo Re, Tracey Simon, Abdul‐Badi Abou‐Samra, Raymond T. Chung, Adeel A. Butt
Journal: Hepatology (2017)

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct‐acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)‐based regimens. We performed a retrospective, population‐based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC‐free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person‐years; P = 0.78 and log‐rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person‐years) compared to those treated with either IFN or DAAs ( P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log‐rank, P = 0.0004). Conclusion: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (H epatology 2018;67:2244‐2253).
Cellular responses to down regulation of human Cdc7 kinase
Authors: Alessia Montagnoli, Pierluigi Tenca, Deborah Brotherton, Daniela Carpani, Sonia Rainoldi, Barbara Valsasina, Corrado Santocanale
Journal: Cancer Research (2004)

2799   DNA replication is a fundamental process for cell proliferation. Mechanisms that control entry into S-phase and proper execution of DNA synthesis are often altered in malignant cells and at the same time are attractive targets for the development of antitumoral agents. DNA replication is a two-step process: first, during the initiation reaction, proteins bound to origin DNA are activated by phosphorylation in order to assemble replication forks and, second, during elongation DNA polymerases together with accessory factors synthesize new DNA strands. Cdc7 kinase is an evolutionary conserved protein that triggers activation of replication origins in several eukaryotic organisms such yeast and xenopus. We have used siRNA technique to down regulate human Cdc7 kinase in a variety of cell lines. Down regulation of Cdc7 causes a substantial decrease in DNA replication and cell proliferation in human cells. We have also observed that response to DNA replication blockade caused by Cdc7 depletion is different both at the cellular and at the molecular level from the one caused by DNA replication elongation inhibitors having clinical applications. From this analysis we suggest that inhibition of Cdc7 kinase and DNA replication initiation reaction could represent a novel and promising approach for the development of efficacious anticancer drugs.
Tamoxifen Resistance in Breast Cancer Is Regulated by the EZH2–ERα–GREB1 Transcriptional Axis
Authors: Yanming Wu, Zhao Zhang, Mauro E. Cenciarini, Cecilia J. Proietti, Matias Amasino, Tao Hong, Mei Yang, Yiji Liao, Huai-Chin Chiang, Virginia G. Kaklamani, Rinath Jeselsohn, Ratna K. Vadlamudi, Tim Hui-Ming Huang, Rong Li, Carmine De Angelis, Xiaoyong Fu, Patricia V. Elizalde, Rachel Schiff, Myles Brown, Kexin Xu
Journal: Cancer Research (2017)

Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG-enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERα cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERα coregulators, converting the antiestrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program.Significance: This study suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program defined within. Cancer Res; 78(3); 671-84. ©2017 AACR.
Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia
Authors: Christine Chen, David Siegel, Martin Gutierrez, Meagan Jacoby, Craig C. Hofmeister, Nashat Gabrail, Rachid Baz, Morten Mau-Sorensen, Jesus G. Berdeja, Michael Savona, Lynn Savoie, Suzanne Trudel, Nuchanan Areethamsirikul, T. J. Unger, Tami Rashal, Tim Hanke, Michael Kauffman, Sharon Shacham, Donna Reece
Journal: Blood (2017)
Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A
Authors: Wouter B Nagengast, Elmire Hartmans, Pilar B Garcia-Allende, Frans T M Peters, Matthijs D Linssen, Maximilian Koch, Marjory Koller, Jolien J J Tjalma, Arend Karrenbeld, Annelies Jorritsma-Smit, Jan H Kleibeuker, Gooitzen M van Dam, Vasilis Ntziachristos
Journal: Gut (2017)

The incidence of oesophageal adenocarcinoma (EAC) is steeply rising. Early lesion detection is a critical factor for improving disease prognosis. We developed and investigated wide-field near-infrared fluorescence molecular endoscopy (NIR-FME), using systemic and topical administration of a fluorescence-labelled antibody against vascular endothelial growth factor (VEGFA). Fourteen patients with Barrett’s oesophagus (BE) underwent endoscopic mucosal resection (EMR) combined with NIR-MFE. From a total of 20 confirmed aberrant lesions identified with NIR-FME, 4 lesions were missed by high-definition (HD) narrowband imaging (NBI) and white-light endoscopy (WLE). This overall 25% detection enhancement advocates NIR-FME as a promising ‘red-flag’ technique for improving early oesophageal lesion detection. ClinicalTrials.gov ID NCT02129933. 

Worldwide, >450 000 people are diagnosed with oesophageal cancer each year. In the western world, at least 80% of these cancers concern EAC.1–4 Late-stage disease detection challenges the efficacy of therapies, resulting in 400 000 deaths each year. Therefore, there is a pressing need for new endoscopic techniques that enable early EAC detection. Endoscopic imaging of targeted fluorescent agents directed against cancer-specific cellular and subcellular moieties, that is, fluorescence molecular endoscopy (FME), has been heralded as a novel method for oesophageal dysplasia and cancer detection.5 FME enables surface and subsurface visualisation of cancer-specific pathophysiology, going beyond the surface-only morphology and tissue discolourations visible with HD-WLE.6–10

In this study, we investigated for the first time real-time NIR-FME of EAC and dysplasia. A pilot study in patients with BE was based on a novel custom-built NIR fluorescence endoscope, paired to a HD-WL clinical scope (online supplementary figure 1) and employed the anti-VEGFA antibody bevacizumab, labelled with the NIR-fluorescent 800CW. The potential of VEGFA as an early discriminating target in BE was first confirmed by immunohistochemistry, demonstrating that all dysplastic tissues expressed VEGFA (online supplementary figure 2).

### Supplementary file 1

[SP1.pdf]

The study furthermore compared systemic versus topical tracer administration during clinical inspection of …
Malaria and the development of pulmonary fibrosis
Authors: Ezra R. Miller, Gary M. Hunninghake
Journal: European Respiratory Journal (2017)

Sorry for the bait-and-switch. This is not a review about the role of parasitic infections and lung scarring. Instead, the manuscript by Sack et al . [1] in this issue of the European Respiratory Journal gives us the opportunity to consider the relationship between air pollution, or "bad air" (the literal translation of the contracted Italian words mala aria ), and the development of, and progression from, early stages of pulmonary fibrosis. Intriguing new evidence suggests that early pulmonary fibrosis is associated with exposure to air pollutants <http://ow.ly/FDor30gAYzS>
Edema and Ulceration of the Lower Extremities—All That’s Red Is Not Infection
Authors: Christina Yek, Nicholas S. Hendren, Arturo R. Dominguez
Journal: JAMA Internal Medicine (2017)

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
Preference phenotypes to facilitate shared decision-making in rheumatoid arthritis
Authors: Liana Fraenkel, W Benjamin Nowell, George Michel, Carole Wiedmeyer
Journal: Annals of the Rheumatic Diseases (2017)

Objective Implementing treat-to-target (TTT) strategies requires that patients with rheumatoid arthritis (RA) and their rheumatologists decide on how best to escalate care when indicated. The objective of this study was to develop preference phenotypes to facilitate shared decision-making at the point of care for patients failing methotrexate monotherapy. Methods We developed a conjoint analysis survey to measure the preferences of patient with RA for triple therapy, biologics and Janus kinase (JAK) inhibitors. The survey included seven attributes: administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information and cost. Each choice set (n=12) included three hypothetical profiles. Preference phenotypes were identified by applying latent class analysis to the conjoint data. Results 1273 participants completed the survey. A five-group solution was chosen based on progressively lower values of the Akaike and Bayesian information criteria. Members of the largest group (group 3: 38.4%) were most strongly impacted by the cost of the medication. The next largest group (group 1: 25.8%) was most strongly influenced by the risk of bothersome side effects. Members of group 2 (11.2%) were also risk averse, but were most concerned with the risk of very rare side effects. Group 4 (6.6%) strongly preferred oral over parenteral medications. Members of group 5 (18.0%) were most strongly and equally influenced by onset of action and the risk of serious infections. Conclusions Treatment preferences of patients with RA can be measured and represented by distinct phenotypes. Our results underscore the variability in patients’ values and the importance of using a shared decision-making approach to implement TTT.