tbuckley/cabot-search huggingface dataset:
A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants
Authors: Katie J. Ryan, Charles C. White, Kruti Patel, Jishu Xu, Marta Olah, Joseph M. Replogle, Michael Frangieh, Maria Cimpean, Phoebe Winn, Allison McHenry, Belinda J. Kaskow, Gail Chan, Nicole Cuerdon, David A. Bennett, Justin D. Boyd, Jaime Imitola, Wassim Elyaman, Philip L. De Jager, Elizabeth M. Bradshaw
Journal: Science Translational Medicine (2017)

A microglial-like cellular model can be used to identify functional consequences of genetic variants associated with neurodegenerative disease.
Mitochondrial dysregulation in BJ-hTERT “survivors” of Cr(VI) genotoxic insult that are resistant to genotoxin-induced clonogenic death.
Authors: Susan M. Ceryak, Therese Lizardo, Ashley Larrimore, Daryl Pritchard, Linan Ha, Steven R. Patierno
Journal: Cancer Research (2006)

5005   Dysregulation of the complex balance between cell growth and death is determinant for neoplastic progression. Certain forms of hexavalent chromium [(Cr(VI)] are human respiratory carcinogens. We have generated sub-populations of BJ-hTERT fibroblasts (transfected with the telomerase gene), which have acquired resistance to Cr (VI)-induced death. DP 5.14 cells were cloned from clonogenic survivors of 24 h exposure to 5 uM Cr (VI), and were markedly resistant to Cr(VI)-induced apoptosis and clonogenic lethality, which was not due to altered uptake. Transport across the outer mitochondrial membrane (OMM) is regulated by a multi-protein pore complex, containing the voltage dependent anion channel (VDAC). Maintenance of OMM permeability is critical for cell survival. Our recent studies have uncovered a novel toxic stress response pathway involving Cr-induced transcriptional up-regulation of the mitochondrial VDAC protein in normal human fibroblasts, and its abrogation in death-resistant DP 5.14 cells. This discovery leads to the intriguing hypothesis that recovery after genotoxic insult may involve the selection of cells with intrinsic or induced mitochondrial dysregulation, leading to death resistance. The aim of the present study was to determine the role of VDAC and mitochondrial function in death resistance after genotoxic insult. We studied VDAC protein expression in BJ-hTERT and DP 5.14 cells by Western blotting. Similar to the gene expression data, 5 uM Na 2 CrO 4  exposure for 24h was associated with a 3-fold increase in VDAC protein expression, which was abrogated in the DP 5.14 subclone. Alterations in VDAC function lead to the mitochondrial membrane permeability transition, which results in the release of the inter-membrane space components into the cytosol. We have previously shown that Cr (VI)-induced apoptosis disrupted mitochondrial membrane potential, and induced cytochrome c release. Therefore, we determined mitochondrial membrane polarity using the cationic JC-9 dye. Cr (VI) enhanced mitochondrial membrane depolarization in BJ-hTERT cells, in a dose-dependent fashion, that was 2 -fold above the control with 9 um Na 2 CrO 4 , but remained unchanged in DP 5.14 cells. In addition, 2 uM exposure to H 2 O 2  for 30 min induced a significant 5.5 -fold increase in mitochondrial membrane depolarization in BJ-hTERT cells , which was only 1.6- fold higher in DP 5.1 4 cells, thus supporting a role for VDAC in death resistance. These results suggest that VDAC may be intrinsically dysregulated in “survivors” of in-situ Cr (VI) treatment. Since acquired resistance to genotoxin-induced death is a hallmark of neoplastic progression, VDAC dysregulation may promote cell survival in the face of genotoxin-induced damage, which in turn may contribute to genomic instability and lead to carcinogenesis. Supported by NIH grants CA107972 to SC, and ES05304 and ES09961 to SRP.
Роль вегетативної дисфункції та її корекції при гастроезофагеальній рефлюксній хворобі
Authors: G.V. Osyodlo, M.V. Radushinska
Journal: GASTROENTEROLOGY (2014)

У статті проаналізовано результати досліджень щодо впливу вегетативної дисфункції на перебіг гастроезофагеальної рефлюксної хвороби, показано доцільність корекції вегетативного дисбалансу фенібутом на тлі антисекреторної терапії пантопразолом, що сприяє покращенню безпосередніх та віддалених результатів лікування.
A Time to Talk
Authors: Dean G. Gianakos
Journal: Annals of Internal Medicine (2017)

Ad Libitum19 December 2017A Time to TalkDean G. Gianakos, MDDean G. Gianakos, MDLynchburg, Virginia (D.G.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-1084 Audio Reading - “A Time to Talk” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Time to Talk," by D.G. Gianakos. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It is difficultto get the news from poemsyet men die miserably every dayfor lackof what is found there.—William Carlos Williams, MD, “Asphodel, That Greeny Flower,” 1955For a friendly ... Author, Article, and Disclosure InformationAffiliations: Lynchburg, Virginia (D.G.G.)Current Author Address: Dean G. Gianakos, MD; e-mail, [email protected]com PreviousarticleNextarticle Advertisement Audio Reading - “A Time to Talk” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Time to Talk," by D.G. Gianakos. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 19 December 2017Volume 167, Issue 12Page: 894KeywordsBloodChartsComputersDrugsElectrode recordingExerciseInsomniaNursesOverweightSuicide ePublished: 19 December 2017 Issue Published: 19 December 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis
Authors: Hai Wang, Zhi-Yong Li, Wen-Xiu Jiang, Bo Liao, Guan-Ting Zhai, Nan Wang, Zhen Zhen, Jian-wen Ruan, Xiao-Bo Long, Heng Wang, Wei-Hong Liu, Geng-Tian Liang, Wei-Min Xu, Atsushi Kato, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2017)
Cooperative Epigenetic Remodeling by TET2 Loss and NRAS Mutation Drives Myeloid Transformation and MEK Inhibitor Sensitivity
Authors: Hiroyoshi Kunimoto, Cem Meydan, Abbas Nazir, Justin Whitfield, Kaitlyn Shank, Franck Rapaport, Rebecca Maher, Elodie Pronier, Sara C. Meyer, Francine E. Garrett-Bakelman, Martin Tallman, Ari Melnick, Ross L. Levine, Alan H. Shih
Journal: Cancer Cell (2017)
Exploring immune checkpoints as potential therapeutic targets in atherosclerosis
Authors: Pascal J H Kusters, Esther Lutgens, Tom T P Seijkens
Journal: Cardiovascular Research (2017)

In the past decades, the inflammatory nature of atherosclerosis has been well-recognized and despite the development of therapeutic strategies targeted at its classical risk factors such as dyslipidemia and hypertension, atherosclerosis remains a major cause of morbidity and mortality. Additional strategies targeting the chronic inflammatory pathways underlying the development of atherosclerosis are therefore required. Interactions between different immune cells result in the secretion of inflammatory mediators, such as cytokines and chemokines, and fuel atherogenesis. Immune checkpoint proteins have a critical role in facilitating immune cell interactions and play an essential role in the development of atherosclerosis. Although the therapeutic potential of these molecules is well-recognized in clinical oncology, the use of immune checkpoint modulators in atherosclerosis is still limited to experimental models. Here, we review recent insights on the role of immune checkpoint proteins in atherosclerosis. Additionally, we explore the therapeutic potential and challenges of immune checkpoint modulating strategies in cardiovascular medicine and we discuss novel therapeutic approaches to target these proteins in atherosclerosis.
Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma
Authors: Amrita Krishnan, Prashant Kapoor, Joycelynne M. Palmer, Ni-Chun Tsai, Shaji Kumar, Sagar Lonial, Myo Htut, Chatchada Karanes, Nitya Nathwani, Michael Rosenzweig, Firoozeh Sahebi, George Somlo, Lupe Duarte, James F. Sanchez, Daniel Auclair, Stephen J. Forman, Jesus G. Berdeja
Journal: Leukemia (2018)
Современные подходы к инициальному и противорецидивному лечению гастроэзофагеальной рефлюксной болезни
Authors: S.M. Tkach
Journal: GASTROENTEROLOGY (2020)

В статье рассмотрены современные подходы к инициальному и противорецидивному лечению гастроэзофагеальной рефлюксной болезни (ГЭРБ), основанные на рекомендациях двух последних американских консенсусов. Согласно этим данным, основными препаратами для лечения ГЭРБ являются ингибиторы протонной помпы (ИПП), которые условно делятся на препараты I и II поколения и могут применяться как в стандартных, так и в двойных и половинных дозах. Препараты II поколения являются более эффективными и безопасными, поскольку меньше зависят от полиморфизма CYP2C19. Сделан вывод, что в большинстве случаев инициальное лечение должно начинаться с применения стандартных или двойных доз ИПП, а поддерживающее — в стандартных или половинных дозах, применяемых по разным схемам — постоянной, интермиттирующей или терапии «по требованию». Наилучшим препаратом для длительного лечения ГЭРБ, особенно при необходимости приема других препаратов, является пантопразол.
Micro(glial)-managing executive function: white matter inflammation drives catatonia
Authors: Sarah E. Pease-Raissi, Jonah R. Chan
Journal: Journal of Clinical Investigation (2017)

White matter abnormalities are prevalent in neuropsychiatric disorders such as schizophrenia, but it is unclear whether these abnormalities represent a cause or consequence of these disorders. Reduced levels of the myelin protein 2′-3′-cyclic nucleotide 3′-phosphodiesterase (CNP) are associated with the schizophrenic symptom catatonia in both humans and mouse models. In this issue of the JCI, Janova et al. show that reduced CNP levels correlate with catatonia and white matter inflammation in human subjects. Furthermore, they demonstrate that microglial ablation prevents and alleviates catatonic signs in Cnp–/– mice, indicating that microglial-mediated inflammation causes catatonia. Together, this study identifies a cellular mechanism by which subtle myelin abnormalities cause low-grade neuroinflammation and catatonic behavior.
Abstract 19909: Ovarian Vein Thrombosis: Risk Factors and Outcomes
Authors: Charles J Lenz, Kevin Cohoon, Robert McBane, Rayya Saadiq, Benjamin Simmons, Ewa Wysokinska, Waldemar Wysokinski
Journal: Circulation (2016)

Introduction: The natural history of ovarian vein thrombosis (OVT) is not currently well described in the literature. Risk factor and recurrence data would help in the development of optimal treatm...
Methylation patterns in serum DNA for early identification of disseminated breast cancer
Authors: Martin Widschwendter, Iona Evans, Allison Jones, Shohreh Ghazali, Daniel Reisel, Andy Ryan, Aleksandra Gentry-Maharaj, Michal Zikan, David Cibula, Johannes Eichner, Marianna Alunni-Fabbroni, Julian Koch, Wolfgang J. Janni, Tobias Paprotka, Timo Wittenberger, Usha Menon, Benjamin Wahl, Brigitte Rack, Harri Lempiäinen
Journal: Genome Medicine (2017)

Monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of substantial quantities of background DNA. We used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer (which will or will not lead to death), respectively, as primary endpoints. A total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs) (HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25% of women who were diagnosed with a fatal BC within 3–6 and 6–12 months of sample donation, respectively, with a specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC. Detection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become clinically apparent.
Modifiable Risk Factors and Prevention of Dementia
Authors: Kristine Yaffe
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
Abstract 16743: Limitations of the Utstein Variables in Predicting Outcomes From Traumatic Out-of-hospital Cardiac Arrest
Authors: Ben Beck, Janet E Bray, Peter Cameron, Lahn Straney, Emily Andrew, Stephen Bernard, Karen Smith
Journal: Circulation (2016)

Background: Given low survival rates in cases of traumatic out-of-hospital cardiac arrest (OHCA), there is a need to identify factors that are associated with outcomes. In this study, we aimed to i...
MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer
Authors: Takahiro Maeda, Masayuki Hiraki, Caining Jin, Hasan Rajabi, Ashujit Tagde, Maroof Alam, Audrey Bouillez, Xiufeng Hu, Yozo Suzuki, Masaaki Miyo, Tsuyoshi Hata, Kunihiko Hinohara, Donald Kufe
Journal: Cancer Research (2017)

The immune checkpoint ligand PD-L1 and the transmembrane mucin MUC1 are upregulated in triple-negative breast cancer (TNBC), where they contribute to its aggressive pathogenesis. Here, we report that genetic or pharmacological targeting of the oncogenic MUC1 subunit MUC1-C is sufficient to suppress PD-L1 expression in TNBC cells. Mechanistic investigations showed that MUC1-C acted to elevate
Chemoradiotherapy as neoadjuvant conversion therapy for merkel cell carcinoma may provide durable disease control.
Authors: John WT Walker, David Olson, Michael Smylie, Kurian Joseph
Journal: Journal of Clinical Oncology (2015)

e20117 Background: Merkel cell carcinoma (MCC) is an uncommon neoplasm, with an annual incidence of 0.44/100 000 persons. 10-year survival for patients with regional disease is < 50%, despite the fact that it is a radio- and chemosensitive cancer. Patients with early stage/operable disease achieve the best outcomes, but there is currently no specific data to guide treatment for patients presenting with unresectable regional (M0) disease. Methods: This project was undertaken as a retrospective quality control analysis. Patients with locally advanced, unresectable MCC treated with neoadjuvant therapy before surgical resections were identified and data was abstracted from an electronic health record. Survival and treatment-related toxicity data was analyzed. Results: 4 male patients treated between 2012 and the present were identified, all presenting with locally advanced, unresectable MCC involving the groin. Mean age at diagnosis was 69 years, and all patients had a performance status of ECOG 0-1. Two patients were treated with neoadjuvant chemoradiotherapy with a platinum doublet prior to wide local excision and sentinel-node biopsy (SLNB) +/- dissection of the involved nodal basin; 2 patients received neoadjuvant chemotherapy before surgery and subsequent post-operative radiation. Radiation dose varied between 48 and 60 Gy. With mean follow-up of 17 months, all 4 patients remain alive with no evidence of disease. Three patients had a pathologic complete response to neoadjuvant therapy; the fourth had micrometastases on SLNB (treated subsequently with radiotherapy). Significant toxicities included fatigue (grade 2, n = 1), febrile neutropenia (grade 3, n = 2), anemia (grade 3, n = 1). Conclusions: MCC is a rare cancer with a lack of evidence to guide therapy; therefore case series such as this have value. Notwithstanding the limitations to our data (retrospective nature, small sample size), carefully selected patients presenting with inoperable, locally advanced MCC can be considered for neoadjuvant conversion therapy. The benefits to this approach may include durable disease control and less long-term treatment-related toxicity with the facilitation of minimally invasive surgery.
Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment
Authors: Musab S. Hommos, Caihong Zeng, Zhihong Liu, Jonathan P. Troost, Avi Z. Rosenberg, Matthew Palmer, Walter K. Kremers, Lynn D. Cornell, Fernando C. Fervenza, Laura Barisoni, Andrew D. Rule
Journal: Kidney International (2017)
Clinical trial design for systemic agents in patients with brain metastases from solid tumours: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group
Authors: D Ross Camidge, Eudocia Q Lee, Nancy U Lin, Kim Margolin, Manmeet S Ahluwalia, Martin Bendszus, Susan M Chang, Janet Dancey, Elisabeth G E de Vries, Gordon J Harris, F Stephen Hodi, Andrew B Lassman, David R Macdonald, David M Peereboom, David Schiff, Ricardo Soffietti, Martin J van den Bent, Jeffrey S Wefel, Patrick Y Wen
Journal: The Lancet Oncology (2017)
Incremental effects of antihypertensive drugs: instrumental variable analysis
Authors: Adam A Markovitz, Jacob A Mack, Brahmajee K Nallamothu, John Z Ayanian, Andrew M Ryan
Journal: BMJ (2017)

To assess the incremental effects of adding extra antihypertensive drugs from a new class to a patient's regimen.Instrumental variable analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). To account for confounding by indication-when treatments seem less effective if they are administered to sicker patients-randomization status was used as the instrumental variable. Patients' randomization status was either intensive (systolic blood pressure target <120 mm Hg) or standard (systolic blood pressure target <140 mm Hg) treatment. Results from instrumental variable models were compared with those from standard multivariable models.Secondary data analysis of a randomized clinical trial conducted at 102 sites in 2010-15.9092 SPRINT participants with hypertension and increased cardiovascular risk but no history of diabetes or stroke.Systolic blood pressure, major cardiovascular events, and serious adverse events.In standard multivariable models not adjusted for confounding by indication, addition of an antihypertensive drug from a new class was associated with modestly lower systolic blood pressure (-1.3 mm Hg, 95% confidence interval -1.6 to -1.0) and no change in major cardiovascular events (absolute risk of events per 1000 patient years, 0.5, 95% confidence interval -1.5 to 2.3). In instrumental variable models, the addition of an antihypertensive drug from a new class led to clinically important reductions in systolic blood pressure (-14.4 mm Hg, -15.6 to -13.3) and fewer major cardiovascular events (absolute risk -6.2, -10.9 to -1.3). Incremental reductions in systolic blood pressure remained large and similar in magnitude for patients already taking drugs from zero, one, two, or three or more drug classes. This finding was consistent across all subgroups of patients. The addition of another antihypertensive drug class was not associated with adverse events in either standard or instrumental variable models.After adjustment for confounding by indication, the addition of a new antihypertensive drug class led to large reductions in systolic blood pressure and major cardiovascular events among patients at high risk for cardiovascular events but without diabetes. Effects on systolic blood pressure persisted across all levels of baseline drug use and all subgroups of patients.
Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development
Authors: Yuting Chen, Martin Widschwendter, Andrew E. Teschendorff
Journal: Genome biology (2017)

Diverse molecular alterations associated with smoking in normal and precursor lung cancer cells have been reported, yet their role in lung cancer etiology remains unclear. A prominent example is hypomethylation of the aryl hydrocarbon-receptor repressor (AHRR) locus, which is observed in blood and squamous epithelial cells of smokers, but not in lung cancer.Using a novel systems-epigenomics algorithm, called SEPIRA, which leverages the power of a large RNA-sequencing expression compendium to infer regulatory activity from messenger RNA expression or DNA methylation (DNAm) profiles, we infer the landscape of binding activity of lung-specific transcription factors (TFs) in lung carcinogenesis. We show that lung-specific TFs become preferentially inactivated in lung cancer and precursor lung cancer lesions and further demonstrate that these results can be derived using only DNAm data. We identify subsets of TFs which become inactivated in precursor cells. Among these regulatory factors, we identify AHR, the aryl hydrocarbon-receptor which controls a healthy immune response in the lung epithelium and whose repressor, AHRR, has recently been implicated in smoking-mediated lung cancer. In addition, we identify FOXJ1, a TF which promotes growth of airway cilia and effective clearance of the lung airway epithelium from carcinogens.We identify TFs, such as AHR, which become inactivated in the earliest stages of lung cancer and which, unlike AHRR hypomethylation, are also inactivated in lung cancer itself. The novel systems-epigenomics algorithm SEPIRA will be useful to the wider epigenome-wide association study community as a means of inferring regulatory activity.