tbuckley/cabot-search huggingface dataset:
Abstract 301: Initial Increase of <i>Klf5</i> and <i>Ppara</i> Expression After Myocardial Ischemia/Reperfusion in Mice Appears to be Critical for Survival
Authors: Christine J Pol, Mesele-Christina Valenti, Sarah M Schumacher, Ancai Yuan, Erhe Gao, Ira J Goldberg, Walter J Koch, Konstantinos Drosatos
Journal: Circulation Research (2016)

Krüppel-like factors (KLF) have important roles in metabolism. We previously found that KLF5 is a positive transcriptional regulator of peroxisome proliferator-activated receptor α ( Ppara) , a central regulator of cardiac fatty acid oxidation (FAO). Mice with cardiomyocyte-specific Klf5 ablation ( α MHC-Klf5 -/- ) had reduced cardiac Ppara expression and FAO. At age 6-12 months these mice develop distinct cardiac dysfunction. The role of PPARα activation in I/R injury is unclear as both beneficial and detrimental effects have been reported. We aimed to study if Ppara expression changes during I/R are driven by KLF5 and explore its protective or detrimental role. Wild type mice were subjected to in vivo I/R or sham surgery. I/R resulted in an initial increase in Ppara , and its target gene pyruvate dehydrogenase kinase 4 ( Pdk4) mRNA after 2h reperfusion, followed by decreased expression after 24h reperfusion. The Ppara expression is associated with parallel changes in cardiac Klf5 mRNA expression. Concurrent, there was a decrease of cardiac FAO-related genes carnitine palmitoyl-transferase 1β ( Cpt1b), very long chain acyl-CoA dehydrogenase (Vlcad), and acyl-CoA oxidase ( Aox) in mice with I/R. To define the cell type causing the temporal changes in Klf5 and Ppara after I/R we isolated primary cardiomyocytes and fibroblasts. Our data suggest a similar effect in primary isolated cardiomyocytes only. Klf5 mRNA expression is increased after 2 hour hypoxia and normalized after 4 hour re-oxygenation in cardiomyocytes, whereas there are no changes after hypoxia/normoxia in fibroblasts. To assess the importance of cardiomyocyte KLF5 in I/R we used α MHC-Klf5 -/- mice. Interestingly, despite reduced FAO, 7 month old αMHC-Klf5 -/- mice subjected to I/R had a marked increase in mortality; 4 of 7 αMHC-Klf5 -/- mice died within the first 24h of reperfusion while no mortality was observed in age-matched wild type mice that underwent I/R. In conclusion, I/R is associated with an increase in Klf5 and Ppara in the first hours of reperfusion followed by a decrease in Klf5 and Ppara , likely accounted for by cardiomyocytes. Increased mortality for α MHC-Klf5 -/- mice with I/R injury suggests that the initial increase may be an adaptive response that is critical for survival.
Phase I/IB Study of Azacitidine and Hedgehog Pathway Inhibition with Sonidegib (LDE225) in Myeloid Malignancies
Authors: Raoul Tibes, Heidi Elizabeth Kosiorek, Amylou Dueck, Jeanne Palmer, James L. Slack, Emily Ann Knight, Saman Khalid Hashmi, James M. Bogenberger, Darci Zblewski, William J. Hogan, Mark R. Litzow, Ruben A Mesa, James M. Foran, Lisa Sproat, Aref Al-Kali
Journal: Blood (2017)
Stem cell treatment: FDA court victory opens way to regulation in US
Authors: Owen Dyer
Journal: BMJ (2019)

Companies that offer treatments in the US that are based on mesenchymal stem cells derived from human fat are likely to face effective regulation by the Food and Drug Administration for the first time, after the agency’s groundbreaking court victory over one of the best known practitioners, US Stem Cell Clinic.

The industry has long argued that, because it uses cells taken from the patient’s own body, its treatments were not drugs and shouldn’t be regulated by the FDA. But the agency contended that the extensive processing of patients’ adipose tissue after its removal from the body made it an “adulterated” product in need of oversight.

Although further appeals are still possible, for now at least US District Judge Ursula Ungaro of the Southern District of Florida seems to have settled that argument decisively in the government’s favour. …
Business Strategies to Promote Health—Reply
Authors: Howard K. Koh, Sara J. Singer, Amy C. Edmondson
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Climate change: the greatest public health threat of the century
Authors: Jeremy Wight, John Middleton
Journal: BMJ (2019)

Stott and colleagues’ editorial is as timely as the Extinction Rebellion protests and Greta Thunberg’s blunt warnings.1 Climate change together with ecosystem damage and biodiversity loss are by far the greatest public health threats of the century, not just globally, but to the United Kingdom.

Public health professionals have a responsibility to recognise, warn about, and help society to deal with threats to …
Abstract 16589: Calcium Sensor Receptor-mediated Effects on Store-Operated Ca2+ Entry and Kv1.5 Channel Activity
Authors: Shanshan Song, Ramon J Ayon, Jason X Yuan
Journal: Circulation (2017)

Calcium sensor receptor (CaSR) is a G-protein coupled receptor (GPCR), and activation of CaSR results in increased cytosolic free Ca2+ concentration ([Ca2+]cyt) due to IP3-dependent Ca2+ release an...
Parkinson's disease in the Western Pacific Region
Authors: Shen-Yang Lim, Ai Huey Tan, Azlina Ahmad-Annuar, Christine Klein, Louis C S Tan, Raymond L Rosales, Roongroj Bhidayasiri, Yih-Ru Wu, Hui-Fang Shang, Andrew H Evans, Pramod K Pal, Nobutaka Hattori, Chong Tin Tan, Beomseok Jeon, Eng-King Tan, Anthony E Lang
Journal: The Lancet Neurology (2019)
TCT-647 Long-Term Clinical Outcomes of Elderly Korean Patients With Multivessel Disease Underwent Percutaneous Coronary Intervention With Drug Eluting Stents
Authors: Kareem Abdelshafi, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Ahmed Mashaly, Yoonjee Park, Won Young Jang, Woohyeun Kim, Jin Oh Na, Cheol Ung Choi, Chang Gyu Park, Hong Seog Seo
Journal: Journal of the American College of Cardiology (2019)
Abstract 15978: Combined Use of Warfarin and Oral P2Y12 Inhibitors in Patients With Atrial Fibrillation and Acute Coronary Syndrome
Authors: William S Jones, Xiaojuan Mi, Manesh R Patel, Rogers Mills, Adrian F Hernandez, Lesley H Curtis
Journal: Circulation (2013)

Background: Although atrial fibrillation (AF) occurs frequently in patients hospitalized with acute coronary syndrome (ACS), strategies for prevention of thromboembolic complications are poorly cha...
Influence of Nanomolar Deltamethrin on the Hallmarks of Primary Cultured Cortical Neuronal Network and the Role of Ryanodine Receptors
Authors: Jing Zheng, Yiyi Yu, Wei Feng, Jing Li, Ju Liu, Chunlei Zhang, Yao Dong, Isaac N. Pessah, Zhengyu Cao
Journal: Environmental Health Perspectives (2019)

Background: The pyrethroid deltamethrin (DM) is broadly used for insect control. Although DM hyperexcites neuronal networks by delaying inactivation of axonal voltage-dependent Na+ channels, this mechanism is unlikely to mediate neurotoxicity at lower exposure levels during critical perinatal periods in mammals. Objectives: We aimed to identify mechanisms by which acute and subchronic DM altered axonal and dendritic growth, patterns of synchronous Ca2+ oscillations (SCOs), and electrical spike activity (ESA) functions critical to neuronal network formation. Methods: Measurements of SCOs using Ca2+ imaging, ESA using microelectrode array (MEA) technology, and dendritic complexity using Sholl analysis were performed in primary murine cortical neurons from wild-type (WT) and/or ryanodine receptor 1 (RyR1T4826I/T4826I) mice between 5 and 14 d in vitro (DIV). [H3]ryanodine binding analysis and a single-channel voltage clamp were utilized to measure engagement of RyRs as a direct target of DM. Results: Neuronal networks responded to DM (30–70 nM) as early as 5 DIV, reducing SCO amplitude and depressing ESA and burst frequencies by 60–70%. DM (10–300 nM) enhanced axonal growth in a nonmonotonic manner. DM≥100 nM enhanced dendritic complexity. DM stabilized channel open states of RyR1, RyR2, and cortical preparations expressing all three isoforms. DM (30 nM) altered gating kinetics of RyR1 channels, increasing mean open time, decreasing mean closed time, and thereby enhancing overall open probability. SCO patterns from cortical networks expressing RyR1T4826I/T4826I were more responsive to DM than WT. RyR1T4826I/T4826I neurons showed inherently longer axonal lengths than WT neurons and maintained less length-promoting responses to nanomolar DM. Conclusions: Our findings suggested that RyRs were sensitive molecular targets of DM with functional consequences likely relevant for mediating abnormal neuronal network connectivity in vitro. https://doi.org/10.1289/EHP4583
Effects of a large-scale distribution of water filters and natural draft rocket-style cookstoves on diarrhea and acute respiratory infection: A cluster-randomized controlled trial in Western Province, Rwanda
Authors: Miles A. Kirby, Corey L. Nagel, Ghislaine Rosa, Laura D. Zambrano, Sanctus Musafiri, Jean de Dieu Ngirabega, Evan A. Thomas, Thomas Clasen
Journal: PLoS Medicine (2019)

Unsafe drinking water and household air pollution (HAP) are major causes of morbidity and mortality among children under 5 in low and middle-income countries. Household water filters and higher-efficiency biomass-burning cookstoves have been widely promoted to improve water quality and reduce fuel use, but there is limited evidence of their health effects when delivered programmatically at scale.
Association of Serum Markers of Oxidative Stress With Incident Major Cardiovascular Events, Cancer Incidence, and All-Cause Mortality in Type 2 Diabetes Patients: Pooled Results From Two Cohort Studies
Authors: Yang Xuan, Xin Gào, Ankita Anusruti, Bernd Holleczek, Eugène H.J.M. Jansen, Dana Clarissa Muhlack, Hermann Brenner, Ben Schöttker
Journal: Diabetes Care (2019)

OBJECTIVE Oxidative stress plays an important role in the pathophysiology of type 2 diabetes mellitus (T2DM). However, associations of biomarkers of oxidative stress with diabetes complications have not yet been addressed in large cohort studies. RESEARCH DESIGN AND METHODS Derivatives of reactive oxygen metabolites (d-ROMs) levels, a proxy for the reactive oxygen species burden, and total thiol levels (TTLs), a proxy for the reductive capacity, were measured in 2,125 patients with T2DM from two German cohort studies of almost equal size at baseline and 3–4 years later. Multivariable adjusted Cox proportional hazards models with time-dependent modeled d-ROMs levels and TTLs were used to assess the associations with incident major cardiovascular events (MCE), cancer incidence, and all-cause mortality. RESULTS In total, 205, 179, and 394 MCE, cancer, and all-cause mortality cases were observed during 6–7 years of follow-up, respectively. Both oxidative stress biomarkers and the d-ROMs-to-TTL ratio were statistically significantly associated with all-cause mortality in both cohorts, and the pooled hazard ratios (HRs) and 95% CIs for top versus bottom tertiles were 2.10 (95% CI 1.43, 3.09) for d-ROMs levels, 0.59 (0.40, 0.87) for TTLs, and 2.50 (1.86, 3.36) for d-ROMs-to-TTL ratio. The d-ROMs-to-TTL ratio was also statistically significantly associated with incident MCE for top versus bottom tertile (1.65 [1.07, 2.54]), but this association did not persist after additional adjustment for chronic diseases. No associations with cancer were detected. CONCLUSIONS The observed strong associations of both biomarkers with mortality suggest an important contribution of an imbalanced redox system to the premature mortality of patients with diabetes.
The Tumor Metabolic Microenvironment: Lessons from Lactate
Authors: Juan C. García-Cañaveras, Li Chen, Joshua D. Rabinowitz
Journal: Cancer Research (2019)

Abstract The extracellular milieu of tumors is generally assumed to be immunosuppressive due in part to metabolic factors. Here, we review methods for probing the tumor metabolic microenvironment. In parallel, we consider the resulting available evidence, with a focus on lactate, which is the most strongly increased metabolite in bulk tumors. Limited microenvironment concentration measurements suggest depletion of glucose and modest accumulation of lactate (less than 2-fold). Isotope tracer measurements show rapid lactate exchange between the tumor and circulation. Such exchange is catalyzed by MCT transporters, which cotransport lactate and protons (H+). Rapid lactate exchange seems at odds with tumor lactate accumulation. We propose a potential resolution to this paradox. Because of the high pH of tumor cells relative to the microenvironment, H+-coupled transport by MCTs tends to drive lactate from the interstitium into tumor cells. Accordingly, lactate may accumulate preferentially in tumor cells, not the microenvironment. Thus, although they are likely subject to other immunosuppressive metabolic factors, tumor immune cells may not experience a high lactate environment. The lack of clarity regarding microenvironmental lactate highlights the general need for careful metabolite measurements in the tumor extracellular milieu.
Naturally acquired immunity against immature<i>Plasmodium falciparum</i>gametocytes
Authors: Kathleen W. Dantzler, Siyuan Ma, Priscilla Ngotho, Will J. R. Stone, Dingyin Tao, Sanna Rijpma, Mariana De Niz, Sandra K. Nilsson Bark, Matthijs M. Jore, Tonke K. Raaijmakers, Angela M. Early, Ceereena Ubaida-Mohien, Leandro Lemgruber, Joseph J. Campo, Andy A. Teng, Timothy Q. Le, Cassidy L. Walker, Patricia Hermand, Philippe Deterre, D. Huw Davies, Phil Felgner, Isabelle Morlais, Dyann F. Wirth, Daniel E. Neafsey, Rhoel R. Dinglasan, Miriam Laufer, Curtis Huttenhower, Karl Seydel, Terrie Taylor, Teun Bousema, Matthias Marti
Journal: Science Translational Medicine (2019)

The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. Immature P. falciparum transmission stages, termed stages I to IV gametocytes, sequester in human bone marrow before release into the circulation as mature stage V gametocytes. This process likely involves interactions between host receptors and potentially immunogenic adhesins on the infected red blood cell (iRBC) surface. Here, we developed a flow cytometry assay to examine immune recognition of live gametocytes of different developmental stages by naturally exposed Malawians. We identified strong antibody recognition of the earliest immature gametocyte-iRBCs (giRBCs) but not mature stage V giRBCs. Candidate surface antigens (n = 30), most of them shared between asexual- and gametocyte-iRBCs, were identified by mass spectrometry and mouse immunizations, as well as correlations between responses by protein microarray and flow cytometry. Naturally acquired responses to a subset of candidate antigens were associated with reduced asexual and gametocyte density, and plasma samples from malaria-infected individuals were able to induce immune clearance of giRBCs in vitro. Infected RBC surface expression of select candidate antigens was validated using specific antibodies, and genetic analysis revealed a subset with minimal variation across strains. Our data demonstrate that humoral immune responses to immature giRBCs and shared iRBC antigens are naturally acquired after malaria exposure. These humoral immune responses may have consequences for malaria transmission potential by clearing developing gametocytes, which could be leveraged for malaria intervention.
Correction: The development of assessment of SpondyloArthritis international society classification criteria for axial spondyloarthritis (part II): Validation and final selection (Annals of the Rheumatic Diseases (2009) 68 (777-783) DOI: 10.1136/ard.2009.108233)
Authors: M. Rudwaleit, D. van de Heijde, R. Landewe
Journal: Annals of the Rheumatic Diseases (2019)

Conflicts of interest (competing interests) for this article were not provided in the paper. This correction now serves to provide conflict of interest statements of individual authors and of ASAS as an organisation with relevance to the years 2008/2009. Conflicts of interest (in the order of authorship): M Rudwaleit: speaking fees and/or consulting fees from Abbott, Centocor, MSD, Pfizer, Roche, Schering-Plough, Wyeth D van der Heijde: research grants and/or consulting fees from Abbott, Amgen, BMS, Centocor, Chugai, Novartis, Pfizer, Schering-Plough, UCB and Wyeth. R Landewe: research grants and/or consulting fees Abbott, Amgen/Immunex, Centocor, MSD (Merck), Shering-Plough, UCB, Wyeth J Listing: no competing interests. N Accoc: speaking fees and/or consultancies from Abbott, Wyeth, UCB, Schering and Novartis. J Brandt: consultancy or speaking fees from Abbott, MSD, Pfizer, Roche. J Braun: nothing declared CT Chou: nothing declared E Collantes-Estevez: research grants or consultation fees from Abbott, Schering Plough and Wyeth M Dougados: research grants, speaking fees and consulting fees from Abbott, Janssen, Lilly, Merck, Novartis, Wyeth, UCB F Huang: no competing interests. J Gu: nothing declared. MA Khan: consultancy and speaker fees from Amgen and Abbott. Y Kirazli: research grants or consultation fees from Allergan, Amgen, Lilly, Novartis, Pfizer and Sandoz. WP Maksymowych: fees for consulting, honoraria, and research grants from Abbott, Amgen-Wyeth, Schering-Plough. H Mielants: no competing interests. IJ Sorensen: lecture fees from Schering-Plough A/S, Wyeth and Abbott; consultancy fees from Bristol-Myers Squibb. S Ozgocmen: no competing interests. E Roussou: no competing interests. R Valle-Onate: no competing interests. U Weber: no competing interests. J Wei: research grants or consultation fee from Abbott, BMS, Chugai, Eisai, Wyeth. J Sieper: honoraria for consultancies and/or being a member of speaker's bureau from Abbott, Amgen, Centocor, Merck, Schering-Plough, Wyeth. ASAS organisation: ASAS has received unrestricted grants for corporate membership from Abbott, Centocor, MSD, Pfizer, Schering-Plough, Wyeth.
Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide
Authors: Chanju Lee, Hyunju Jeong, Younghyeon Bae, Kyungmoon Shin, Sinwoo Kang, Hwikyung Kim, Jayoung Oh, Hyunsu Bae
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating immune cells. Macrophages are broadly categorized as M1 or M2 types, and TAMs have been shown to express an M2-like phenotype. TAMs promote tumor progression and contribute to resistance to chemotherapies. Therefore, M2-like TAMs are potential targets for the cancer immunotherapy. In this study, we targeted M2-like TAMs using a hybrid peptide, MEL-dKLA, composed of melittin (MEL), which binds preferentially to M2-like TAMs, and the pro-apoptotic peptide d (KLAKLAK)<sub>2</sub> (dKLA), which induces mitochondrial death after cell membrane penetration. <h3>Methods</h3> The M1 or M2-differentiated RAW264.7 cells were used for mitochondrial colocalization and apoptosis test in vitro. For in vivo study, the murine Lewis lung carcinoma cells were inoculated subcutaneously in the right flank of mouse. The dKLA, MEL and MEL-dKLA peptides were intraperitoneally injected at 175 nmol/kg every 3 days. Flow cytometry analysis of tumor-associated macrophages and immunofluorescence staining were performed to investigate the immunotherapeutic effects of MEL-dKLA. <h3>Results</h3> We showed that MEL-dKLA induced selective cell death of M2 macrophages in vitro, whereas MEL did not disrupt the mitochondrial membrane. We also showed that MEL-dKLA selectively targeted M2-like TAMs without affecting other leukocytes, such as T cells and dendritic cells, in vivo. These features resulted in lower tumor growth rates, tumor weights, and angiogenesis in vivo. Importantly, although both MEL and MEL-dKLA reduced numbers of CD206<sup>+</sup> M2-like TAMs in tumors, only MEL-dKLA induced apoptosis in CD206<sup>+</sup> M2-like TAMs, and MEL did not induce cell death. <h3>Conclusion</h3> Taken together, our study demonstrated that MEL-dKLA could be used to target M2-like TAMs as a promising cancer therapeutic agent.
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
Authors: Laure Frésard, Craig Smail, Nicole M. Ferraro, Nicole A. Teran, Xin Li, Kevin S. Smith, Devon Bonner, Kristin D. Kernohan, Shruti Marwaha, Zachary Zappala, Brunilda Balliu, Joe R. Davis, Boxiang Liu, Cameron J. Prybol, Jennefer N. Kohler, Diane B. Zastrow, Chloe M. Reuter, Dianna G. Fisk, Megan E. Grove, Jean M. Davidson, Taila Hartley, Ruchi Joshi, Benjamin J. Strober, Sowmithri Utiramerur, Lars Lind, Erik Ingelsson, Alexis Battle, Gill Bejerano, Jonathan A. Bernstein, Euan A. Ashley, Kym M. Boycott, Jason D. Merker, Matthew T. Wheeler, Stephen B. Montgomery
Journal: Nature Medicine (2019)