tbuckley/cabot-search huggingface dataset:
Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial
Authors: Vanessa C. Harris, Bastiaan W. Haak, Scott A. Handley, Baoming Jiang, Daniel E. Velasquez, Barry L. Hykes, Lindsay Droit, Guy A.M. Berbers, Elles Marleen Kemper, Ester M.M. van Leeuwen, Michael Boele van Hensbroek, Willem Joost Wiersinga
Journal: Cell Host & Microbe (2018)

Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV immunogenicity was boosted at 7 days in the narrow-spectrum group. Further, antibiotics increased fecal shedding of RV while also rapidly altering gut bacterial beta diversity. Beta diversity associated with RVV immunogenicity boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and RV shedders were identified. Despite the negative primary endpoint, this study demonstrates that microbiota modification alters the immune response to RVV and supports further exploration of microbiome manipulation to improve RVV immunogenicity.
Abstract 492: Downregulation of microRNA-17-5p promotes EMT by targeting vimentin in colorectal cancer
Authors: Tea Won Kim, Yeo Song Lee, Hye Kyung Hong, Su Jeong Song, Nak Hyeon Yun, Yong Beom Cho
Journal: Cancer Research (2018)

Abstract Background: Colorectal cancer (CRC) is one of the most frequent forms of cancer worldwide. Cells with abnormal growth have the ability to invade or spread to other parts of the body (metastasis). Metastasis is the most common cause of death in CRC patients and activation of epithelial-mesenchymal transition (EMT) triggers metastasis. Thus, it is important to understand the mechanisms of EMT to increase the survival rate of CRC. MicroRNA-17 (miRNA-17) has been proven to be significantly higher in CRC tissues than normal tissues. However, there are few papers about the role of miRNA-17 in CRC metastasis. Therefore, in this study, we evaluated the mechanism underlying miRNA-17-5p related EMT in colon cancer cells. Methods: Expression level of miRNA-17-5p as well as target mRNA were analyzed in HCT-15, HT29, LoVo, SW480 and COLO205 cell lines. In order to evaluate the correlation between miRNA-17-5p and EMT phenomenon, selected cell lines were transiently transfected either miRNA-17-5p mimic or miRNA-17-5p inhibitor and then phenotyping studies were conducted. Moreover, to find out the direct target of miRNA-17-5p, we performed AGO2 immunoprecipitation in each colon cancer cell lines. Results: Real-time PCR revealed that miRNA-17-5p expression reversely correlated with vimentin expression in five colon cancer cell lines. Overexpression of miRNA-17-5p inhibited vimentin expression, cell migration and cell invasion in both LoVo and HT29 cells. On the other hand, inhibition of miRNA-17-5p promoted vimentin expression, cell migration and cell invasion in the same parallel cell lines. Through AGO2 immunoprecipitation analysis, we observed that miRNA-17-5p directly bind to vimentin 3'UTR to influence its stability and expression at the transcriptional level. Conclusion: Our data demonstrated that down-regulated miRNA-17-5p promotes colon cancer cell migration and invasion by regulating vimentin expression. These findings propose that miRNA-17-5p may serve as a potential prognostic biomarker in colorectal cancer. Citation Format: Tea Won Kim, Yeo Song Lee, Hye Kyung Hong, Su Jeong Song, Nak Hyeon Yun, Yong Beom Cho. Downregulation of microRNA-17-5p promotes EMT by targeting vimentin in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 492.
A Refugee’s Journey
Authors: Khristopher M. Nguyen
Journal: JAMA (2018)

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 SY32-01: Knowledge management and decision support for commonly tested susceptibility mutations
Authors: Giovanni Parmigiani, Danielle Braun, Kevin S. Hughes
Journal: Cancer Research (2018)

Abstract Challenges: Germline testing for inherited genetic susceptibility to cancer has become cheaper and widely used. Multigene panels now routinely test 25 to 123 genes. Health care providers, including clinicians and genetic counselors, must interpret results, assess the risk of various cancers, and advise on clinical management strategies. Aside from a small number of well-known genes, clinicians lack simple and reliable tools to personalize prevention decisions for individuals who test positive. Evidence on the types of cancer associated with susceptibility genes, and on the magnitude of increased risks associated with a mutation, is emerging at a fast rate. However, a large number of combinations of cancer type and gene variant needs to be considered. No comprehensive databases exist, information is dispersed over a vast number of published studies, the quality of the studies is uneven, and the data presented are seldom directly applicable to precision prevention decisions, which require absolute risk estimates. Thus, when assessing cancer risks for mutation carriers, clinical practice can take little advantage of the impressive scientific advancements in this field. Approaches: This presentation describes ongoing work to develop tools that could facilitate the translation into clinical practice of research results that would otherwise be difficult to access, systematize, interpret, and convert into actionable knowledge. The long-term goal should be to develop a clinical decision-support system that allows a clinician to enter important factors about a patient with a mutation and immediately receive patient-specific absolute risk estimates. The foundation for the clinical decision-support system needs to be laid by systematically collecting and curating studies on gene cancer associations and, ideally, developing a public access knowledge base for researchers and health care providers. These steps need computational tools for efficient implementations of this plan and for sustainable long-term updating of the knowledge base and decision-support system. The ask2me.org project and the data science behind it are attempting to achieve some of these steps. This project will be used as an illustration throughout. Impact: Progress in this area will have a direct clinical impact by providing patient-specific absolute risk estimates. These risk estimates will, in turn, lead to more carefully personalized prevention and management for individuals undergoing susceptibility testing, and will help us optimize screening and behavioral interventions to reduce risk. Citation Format: Giovanni Parmigiani, Danielle Braun, Kevin S. Hughes. Knowledge management and decision support for commonly tested susceptibility mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY32-01.
Ex Vivo Functionality of 3D Bioprinted Corneal Endothelium Engineered with Ribonuclease 5‐Overexpressing Human Corneal Endothelial Cells
Authors: Kyoung Woo Kim, Soo Jin Lee, Soo Hyun Park, Jae Chan Kim
Journal: Advanced Healthcare Materials (2018)

Abstract Human corneal endothelial cells (HCECs) are scarcely proliferative in vivo. The cultured HCECs engineered to overexpress ribonuclease (RNase) 5 (R5‐HCECs) are prepared after transient transfection with RNase 5 plasmid vector. As candidate targets of R5‐HCECs for enhancement of cellular proliferation and survival of R5‐HCECs, programmed cell death protein 4 is inhibited, and cyclin D1 and cyclin E1 are activated. The cultured R5‐HCECs and control HCECs on lyophilized amniotic membrane (AM) are deposited as a carrier by extrusion‐based 3D bioprinting to prepare transplantable RNase 5 vector‐transfected HCECs–laden AM graft (R5‐Graft) and the control HCECs–laden AM graft (Ct‐Graft), respectively. The ready‐to‐use R5‐Graft shows clearer basolateral expression of Na + ‐K + ATPase pump and higher cell confluency than Ct‐Graft. From 2 weeks after graft transplantation, both R5‐Graft and Ct‐Graft start restoring clarity of the rabbit corneas, and their central corneal edema are much less than those in the control group at 3 and 4 weeks. The ex vivo expression of corneal endothelial phenotypical markers is clear in R5‐Grafs rather than in Ct‐Grafts at 4 weeks. In conclusion, the fabricated corneal endothelium with cultured HCECs easily survives and functions as corneal endothelium in vivo. Furthermore, the use of the cultured HCECs engineered to overexpress RNase 5 (R5‐HCECs) may be an option to obtain higher graft cellularity and to enhance the function of transplanted grafts.
Progesterone Antagonizes the Vasoprotective Effect of Estrogen on Antioxidant Enzyme Expression and Function
Authors: KerstinWassmann, SvenWassmann, GeorgNickenig
Journal: Circulation Research (2005)

Oxidative stress plays an important role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzymes. Estrogens exert antioxidative effects in the vasculature; however, cotreatment with progesterone may abrogate the vasoprotective effects of estrogen. Therefore, the effects of progesterone on the production of reactive oxygen species (ROS) and expression and function of antioxidant and oxidant enzymes were investigated in cultured vascular smooth muscle cells (VSMCs) and vascular tissue of mice. Progesterone time- and concentration-dependently downregulated extracellular superoxide dismutase (ecSOD) and manganese superoxide dismutase (MnSOD) expression and enzyme activity and reversed 17β-estradiol–induced overexpression of ecSOD and MnSOD in VSMCs. Nuclear run-on assays revealed that progesterone decreases MnSOD and ecSOD transcription rates. Consequently, progesterone increased ROS release in VSMCs that was prevented by concomitant treatment with 17β-estradiol....
Maintenance Treatment for Patients With Mantle Cell Lymphoma
Authors: Liat Vidal, Anat Gafter‐Gvili, Martin Dreyling, Michele Ghielmini, Mathias Witzens‐Harig, Ofer Shpilberg, Michael Unterhalt, Mathias Rummel, Ronit Gurion
Journal: HemaSphere (2018)

Current treatment of patient with mantle cell lymphoma (MCL) is insufficient and does not result in cure. To assess the efficacy and safety of maintenance therapy for patients with MCL, we performed a systematic review and meta-analysis of randomized controlled trials. Six trials randomizing 858 patients were included in the meta-analysis. In 5 trials, maintenance therapy consisted of rituximab. The pooled hazard ratio (HR) of death with rituximab maintenance compared to observation was 0.79, 95% CI 0.58 to 1.06 (4 trials, 737 patients). Progression free survival was longer with rituximab maintenance in each of the trials and in the pooled analysis (HR 0.58, 95% CI 0.45-0.73). The risk of neutropenia was higher with maintenance compared to observation risk ratio (RR) 1.31, 95% CI 1.03 to 1.66. None of the trials reported on quality of life outcomes. The grade 3 to 4 infection rate was 7% in each of the treatment groups. The risk of grade 3 to 4 infection was not affected by allocation to maintenance. Rituximab maintenance is recommended after R-CHOP or R-cytarabine-containing induction in the frontline setting for transplant eligible and ineligible patients, and after R-CHOP in the relapse setting. It is unclear if maintenance is of benefit after different induction chemotherapy such as bendamustine or fludarabine. It is too early to conclude on other type of maintenance for MCL patients.
Abstract 83: Effect of Therapeutic Hypothermia on Oxygenation Index in Rat Model of Cardiac Arrest
Authors: HaifangYu, LuYin, PingGong, JiangangWang, ZhengfeiYang, ShenZhao, JieQian, XiaoboWu, JenaCahoon, WanchunTang
Journal: Circulation (2014)

Introduction: Therapeutic hypothermia improves the outcomes of cerebral function after resuscitation from cardiac arrest (CA). The effect of therapeutic hypothermia on post resuscitation pulmonary function, however, is less known. In the present study, we investigated the effect of therapeutic hypothermia on oxygenation index, a sensitive index of pulmonary function,in a rat model of cardiac arrest and resuscitation. Hypothesis: We hypothesize that during therapeutic mild hypothermia in a rat model of cardiac arrest, the pulmonary function following resuscitation is less impaired when compare to normothermia. Methods: Twenty-one male Sprague-Dawley rats were randomized into three groups: 1) control group (control, n=5): the normothermic rats only received anesthesia and the surgical procedure as the other groups without ventricular fibrillation (VF); 2) normothermia group (NT, n=7): the normothermic rats were subjected to induced VF for 8 mins followed by 8 mins of cardiopulmonary resuscitation (CPR); 3) ...
Genetic Manipulation of the Rabbit Heart via Transgenesis
Authors: JeanneJames, AtsushiSanbe, KarenYager, LisaMartin, RaisaKlevitsky, JeffreyRobbins
Journal: Circulation (2000)

Background—Transgenesis using cardiac-specific expression has been valuable in exploring cardiac structure-function relationships. To date, cardiac-selective studies have been confined to the mouse. However, the utility of the mouse is limited in certain, possibly critical, aspects with respect to cardiovascular function. Methods and Results—To establish the potential validity of transgenic methodology for remodeling a larger mammalian heart, we explored cardiac-selective expression in transgenic rabbits. The murine α- and β-cardiac myosin heavy chain gene promoters were used to express a reporter gene, and transgene expression was quantified in cardiac, skeletal, and smooth muscles as well as in nonmuscle tissues. Although neither promoter exactly mimics endogenous patterns of myosin heavy chain expression, both are able to drive high levels of transgene expression in the cardiac compartment. Neither promoter is active in smooth muscle or nonmuscle tissues. Conclusions—Directed organ-specific expression ...
Abstract 3914: ZW49, a HER2-targeted biparatopic antibody-drug conjugate for the treatment of HER2-expressing cancers
Authors: Kevin J. Hamblett, Phil W. Hammond, Stuart D. Barnscher, Vincent K. Fung, Rupert H. Davies, Grant R. Wickman, Andrea Hernandez, Tong Ding, Adam S. Galey, Geoffrey C. Winters, Jamie R. Rich, John S. Babcook
Journal: Cancer Research (2018)

Abstract Therapies targeting HER2 have transformed the treatment of patients with HER2-expressing breast and gastric cancers. Unfortunately, many patients recur following HER2-targeted treatments and new therapies are needed. Multiple antibody-drug conjugate (ADC) technologies are being explored in this setting, some of which utilize the anti-HER2 antibody trastuzumab. Here we present the preclinical characterization of a new anti-HER2 biparatopic ADC, ZW49, which is generated from the conjugation of a novel N-acyl sulfonamide auristatin payload to the inter-chain disulfide bond cysteines of the bispecific anti-HER2 IgG1 antibody ZW25, via a protease cleavable linker. A series of in vitro and in vivo experiments were performed to characterize ZW49 as a potential therapeutic candidate. In cellular binding assays, it was confirmed that the payload conjugation to ZW25 did not affect the antibody's binding to HER2-expressing cells. ZW49 displayed potent in vitro cytotoxicity in multiple cancer cell lines expressing HER2 and was efficacious in multiple patient-derived xenograft (PDX) models. In mice bearing the HBCx-13b HER2 3+ PDX, two doses of ZW49 administered two weeks apart generated tumor regressions. Furthermore, preliminary results from PDX models with lower levels of HER2 expression treated with ZW49 also generated regressions. In nonhuman primates ZW49 administered intravenously every two weeks for three doses was well tolerated. Based on these findings, we are proceeding with further development of ZW49 as a therapeutic candidate in HER2-expressing cancers. Citation Format: Kevin J. Hamblett, Phil W. Hammond, Stuart D. Barnscher, Vincent K. Fung, Rupert H. Davies, Grant R. Wickman, Andrea Hernandez, Tong Ding, Adam S. Galey, Geoffrey C. Winters, Jamie R. Rich, John S. Babcook. ZW49, a HER2-targeted biparatopic antibody-drug conjugate for the treatment of HER2-expressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3914.
Arrhythmia Burden in Elderly Patients With Severe Aortic Stenosis as Determined by Continuous Electrocardiographic Recording
Authors: Marina Urena, Salim Hayek, Asim N. Cheema, Vicenç Serra, Ignacio J. Amat-Santos, Luis Nombela-Franco, Henrique B. Ribeiro, Ricardo Allende, Jean-Michel Paradis, Eric Dumont, Vinod H. Thourani, Vasilis Babaliaros, Jaume Francisco Pascual, Carlos Cortés, Bruno García del Blanco, François Philippon, Stamatios Lerakis, Josep Rodés-Cabau
Journal: Circulation (2014)

This study sought to evaluate the prevalence of previously undiagnosed arrhythmias in candidates for transcatheter aortic valve replacement (TAVR) and to determine the impact on therapy changes and arrhythmic events after the procedure.A total of 435 candidates for TAVR underwent 24-hour continuous ECG monitoring the day before the procedure. Newly diagnosed arrhythmias were observed in 70 patients (16.1%) before TAVR: paroxysmal atrial fibrillation (AF)/atrial tachycardia (AT) in 28, advanced atrioventricular block or severe bradycardia in 24, nonsustained ventricular tachycardia in 26, and intermittent left bundle-branch block in 3 patients. All arrhythmic events but one were asymptomatic and led to a therapy change in 43% of patients. In patients without known AF/AT, the occurrence of AF/AT during 24-hour ECG recording was associated with a higher rate of 30-day cerebrovascular events (7.1% versus 0.4%; P=0.030). Among the 53 patients with new-onset AF/AT after TAVR, 30.2% had newly diagnosed paroxysmal AF/AT before the procedure. In patients who needed permanent pacemaker implantation after the procedure (n=35), 31.4% had newly diagnosed advanced atrioventricular block or severe bradycardia before TAVR. New-onset persistent left bundle-branch block after TAVR occurred in 37 patients, 8.1% of whom had intermittent left bundle-branch block before the procedure.Newly diagnosed arrhythmias were observed in approximately a fifth of TAVR candidates, led to a higher rate of cerebrovascular events, and accounted for a third of arrhythmic events after the procedure. This high arrhythmia burden highlights the importance of an early diagnosis of arrhythmic events in such patients to implement the appropriate therapeutic measures earlier.
Abstract 5215: Vitamin D receptor regulates intestinal barriers in colon cancer
Authors: Yong-guo Zhang, Rong Lu, Danika Bakke, Yinglin Xia, Jun Sun
Journal: Cancer Research (2018)

Abstract Background Vitamin D and Vitamin D receptor (VDR) play important roles in the development of colon cancer. Tight junction structures are essential in intestinal barrier integrity, inflammation, and cancer. The disruption of tight junctions is a common manifestation of various diseases including cancers. Claudin-5 is a tight junction protein that is expressed in epithelia and endothelia and form paracellular barriers and pores that determine permeability. It is downregulated in colon cancer. Although VDR and Claudin-5 are all involved in colon cancer, it remains unclear whether they are closely related or function independently. Methods In the current study, we investigate the novel role of VDR in regulating Claudin-5, using whole body VDR knockout mice (VDR-/-) and intestinal epithelial VDR knockout mice (VDRΔIEC). In vitro, VDR-/- embryonic fibroblasts (MEF) cells, cultured human intestinal epithelial cells, organoids, and human colon cancer samples were used to determine the molecular mechanism. Results In intestinal samples of colon cancer patients, VDR expression is low, whereas the expression of Claudin-5 is also decreased. In the colon of VDR-/- mice and VDRΔIEC mice, deletion of VDR led to lower claudin-5 at the protein and mRNA levels. This observation was also confirmed by immunostaining of Claudin-5. In VDR-/- MEF cells, both Western blot and real time PCR revealed that VDR deletion led to lower protein and mRNA levels of claudin-5 in cells without any treatment. Vitamin D3 is known to increase VDR expression and activate VDR signaling. Protein and mRNA levels of Claudin-5 were significantly elevated in mice, mouse organoids, and human intestinal epithelial SKCO15 cells treated with 1, 25 vitamin D3. In contrast, knockdown of Claudin-5 using siRNA did not change the expression level of VDR protein in human colonic epithelial cells. Our data suggest that the Claudin-5 gene is a downstream target of the VDR signaling pathway. Conclusion Taken together, we show that VDR is important for the maintenance of physiological level of Claudin-5. This study also reveals a complex role for vitamin D/VDR regulation of intestinal barrier functions in colon cancer. Citation Format: Yong-guo Zhang, Rong Lu, Danika Bakke, Yinglin Xia, Jun Sun. Vitamin D receptor regulates intestinal barriers in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5215.
Abstract 20853: Knock Down of Activated FOXO Transcription Factors in the Heart in the Lamin Null Mice Attenuates the Phenotype and Prolongs Survival
Authors: Gaelle Auguste, Priyatansh Gurha, Cristian Coarfa, Raffaella Lombardi, Sirisha Marreddy, James T Willerson, Ali J Marian
Journal: Circulation (2017)

Rationale: LMNA (Lamin A/C) is a nuclear membrane protein that interacts with the genome and regulates gene expression. Mutations in the LMNA gene cause several distinct diseases, referred to as la...