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REVIEW
Deirdre K Tobias, Jordi Merino, Abrar Ahmad, Catherine Aiken, Jamie L Benham, Dhanasekaran Bodhini, Amy L Clark, Kevin Colclough, Rosa Corcoy, Sara J Cromer, Daisy Duan, Jamie L Felton, Ellen C Francis, Pieter Gillard, Véronique Gingras, Romy Gaillard, Eram Haider, Alice Hughes, Jennifer M Ikle, Laura M Jacobsen, Anna R Kahkoska, Jarno L T Kettunen, Raymond J Kreienkamp, Lee-Ling Lim, Jonna M E Männistö, Robert Massey, Niamh-Maire Mclennan, Rachel G Miller, Mario Luca Morieri, Jasper Most, Rochelle N Naylor, Bige Ozkan, Kashyap Amratlal Patel, Scott J Pilla, Katsiaryna Prystupa, Sridharan Raghavan, Mary R Rooney, Martin Schön, Zhila Semnani-Azad, Magdalena Sevilla-Gonzalez, Pernille Svalastoga, Wubet Worku Takele, Claudia Ha-Ting Tam, Anne Cathrine B Thuesen, Mustafa Tosur, Amelia S Wallace, Caroline C Wang, Jessie J Wong, Jennifer M Yamamoto, Katherine Young, Chloé Amouyal, Mette K Andersen, Maxine P Bonham, Mingling Chen, Feifei Cheng, Tinashe Chikowore, Sian C Chivers, Christoffer Clemmensen, Dana Dabelea, Adem Y Dawed, Aaron J Deutsch, Laura T Dickens, Linda A DiMeglio, Monika Dudenhöffer-Pfeifer, Carmella Evans-Molina, María Mercè Fernández-Balsells, Hugo Fitipaldi, Stephanie L Fitzpatrick, Stephen E Gitelman, Mark O Goodarzi, Jessica A Grieger, Marta Guasch-Ferré, Nahal Habibi, Torben Hansen, Chuiguo Huang, Arianna Harris-Kawano, Heba M Ismail, Benjamin Hoag, Randi K Johnson, Angus G Jones, Robert W Koivula, Aaron Leong, Gloria K W Leung, Ingrid M Libman, Kai Liu, S Alice Long, William L Lowe, Robert W Morton, Ayesha A Motala, Suna Onengut-Gumuscu, James S Pankow, Maleesa Pathirana, Sofia Pazmino, Dianna Perez, John R Petrie, Camille E Powe, Alejandra Quinteros, Rashmi Jain, Debashree Ray, Mathias Ried-Larsen, Zeb Saeed, Vanessa Santhakumar, Sarah Kanbour, Sudipa Sarkar, Gabriela S F Monaco, Denise M Scholtens, Elizabeth Selvin, Wayne Huey-Herng Sheu, Cate Speake, Maggie A Stanislawski, Nele Steenackers, Andrea K Steck, Norbert Stefan, Julie Støy, Rachael Taylor, Sok Cin Tye, Gebresilasea Gendisha Ukke, Marzhan Urazbayeva, Bart Van der Schueren, Camille Vatier, John M Wentworth, Wesley Hannah, Sara L White, Gechang Yu, Yingchai Zhang, Shao J Zhou, Jacques Beltrand, Michel Polak, Ingvild Aukrust, Elisa de Franco, Sarah E Flanagan, Kristin A Maloney, Andrew McGovern, Janne Molnes, Mariam Nakabuye, Pål Rasmus Njølstad, Hugo Pomares-Millan, Michele Provenzano, Cécile Saint-Martin, Cuilin Zhang, Yeyi Zhu, Sungyoung Auh, Russell de Souza, Andrea J Fawcett, Chandra Gruber, Eskedar Getie Mekonnen, Emily Mixter, Diana Sherifali, Robert H Eckel, John J Nolan, Louis H Philipson, Rebecca J Brown, Liana K Billings, Kristen Boyle, Tina Costacou, John M Dennis, Jose C Florez, Anna L Gloyn, Maria F Gomez, Peter A Gottlieb, Siri Atma W Greeley, Kurt Griffin, Andrew T Hattersley, Irl B Hirsch, Marie-France Hivert, Korey K Hood, Jami L Josefson, Soo Heon Kwak, Lori M Laffel, Siew S Lim, Ruth J F Loos, Ronald C W Ma, Chantal Mathieu, Nestoras Mathioudakis, James B Meigs, Shivani Misra, Viswanathan Mohan, Rinki Murphy, Richard Oram, Katharine R Owen, Susan E Ozanne, Ewan R Pearson, Wei Perng, Toni I Pollin, Rodica Pop-Busui, Richard E Pratley, Leanne M Redman, Maria J Redondo, Rebecca M Reynolds, Robert K Semple, Jennifer L Sherr, Emily K Sims, Arianne Sweeting, Tiinamaija Tuomi, Miriam S Udler, Kimberly K Vesco, Tina Vilsbøll, Robert Wagner, Stephen S Rich, Paul W Franks
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications...
October 5, 2023: Nature Medicine
#2
JOURNAL ARTICLE
Rinki Murphy, Kevin Colclough, Toni I Pollin, Jennifer M Ikle, Pernille Svalastoga, Kristin A Maloney, Cécile Saint-Martin, Janne Molnes, Shivani Misra, Ingvild Aukrust, Elisa de Franco, Sarah E Flanagan, Pål R Njølstad, Liana K Billings, Katharine R Owen, Anna L Gloyn
BACKGROUND: Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field...
October 5, 2023: Commun Med (Lond)
#3
JOURNAL ARTICLE
Venktesh S Shirure, Sergey Yechikov, Bhupinder S Shergill, Tima Dehghani, Anton V Block, Harkanwalpreet Sodhi, Alyssa Panitch, Steven C George
A feature of severe COVID-19 is the onset of an acute and intense systemic inflammatory response referred to as the "cytokine storm". The cytokine storm is characterized by high serum levels of inflammatory cytokines and the subsequent transport of inflammatory cells to damaging levels in vital organs ( e.g. , myocarditis). Immune trafficking and its effect on underlying tissues ( e.g. , myocardium) are challenging to observe at a high spatial and temporal resolution in mouse models. In this study, we created a vascularized organ-on-a-chip system to mimic cytokine storm-like conditions and tested the effectiveness of a novel multivalent selectin-targeting carbohydrate conjugate (composed of DS - dermatan sulfate and IkL - a selectin-binding peptide, termed DS-IkL) in blocking infiltration of polymorphonuclear leukocytes (PMN)...
June 6, 2023: Lab on a Chip
#4
Rinki Murphy, Kevin Colclough, Toni I Pollin, Jennifer M Ikle, Pernille Svalastoga, Kristin A Maloney, Cécile Saint-Martin, Janne Molnes, Shivani Misra, Ingvild Aukrust, AIElisa de Franco, Sarah E Flanagan, Pål R Njølstad, Liana K Billings, Katharine R Owen, Anna L Gloyn
UNLABELLED: Monogenic forms of diabetes present opportunities for precision medicine as identification of the underlying genetic cause has implications for treatment and prognosis. However, genetic testing remains inconsistent across countries and health providers, often resulting in both missed diagnosis and misclassification of diabetes type. One of the barriers to deploying genetic testing is uncertainty over whom to test as the clinical features for monogenic diabetes overlap with those for both type 1 and type 2 diabetes...
April 19, 2023: medRxiv
#5
JOURNAL ARTICLE
Yasaman Khaksarfard, Ahmad Bagheri, Amir Abbas Rafati
In this paper, the surfactant-modified clinoptilolite zeolite (with two methods) were used to remove diclofenac sodium (DFS) as a widely used drug in an aqueous solution. Clinoptilolite was modified by using pure cationic surfactant (cetyltrimethylammonium chloride, CTAC) and the mixed surfactants of CTAC + Triton-X100 (TX100). In the new approach, the synergistic effects between CTAC and TX100 were determined by surface tension measurements in different mole fractions and the optimum ratio (y1 ≈ 0...
April 18, 2023: Journal of Colloid and Interface Science
#6
JOURNAL ARTICLE
Yamei Tu, Xiaoqi Wang, Rui Qiu, Han-Wei Shen
The Internet of Food (IoF) is an emerging field in smart foodsheds, involving the creation of a knowledge graph (KG) about the environment, agriculture, food, diet, and health. However, the heterogeneity and size of the KG present challenges for downstream tasks, such as information retrieval and interactive exploration. To address those challenges, we propose an interactive knowledge and learning environment (IKLE) that integrates three programming and modeling languages to support multiple downstream tasks in the analysis pipeline...
April 3, 2023: IEEE Computer Graphics and Applications
#7
JOURNAL ARTICLE
Katia K Mattis, Nicole A J Krentz, Christoph Metzendorf, Fernando Abaitua, Aliya F Spigelman, Han Sun, Jennifer M Ikle, Swaraj Thaman, Antje K Rottner, Austin Bautista, Eugenia Mazzaferro, Marta Perez-Alcantara, Jocelyn E Manning Fox, Jason M Torres, Agata Wesolowska-Andersen, Grace Z Yu, Anubha Mahajan, Anders Larsson, Patrick E MacDonald, Benjamin Davies, Marcel den Hoed, Anna L Gloyn
AIMS/HYPOTHESIS: Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycaemic traits. However, little is known about the function of the zinc finger transcription factor Ras-responsive element binding protein 1 (RREB1) in glucose homeostasis or how changes in its expression and/or function influence diabetes risk. METHODS: A zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo...
January 12, 2023: Diabetologia
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JOURNAL ARTICLE
Jennifer M Ikle, Robert C Tryon, Soma S Singareddy, Nathaniel W York, Maria S Remedi, Colin G Nichols
ATP-sensitive potassium channel (KATP )gain- (GOF) and loss-of-function (LOF) mutations underlie human neonatal diabetes mellitus (NDM) and hyperinsulinism (HI), respectively. While transgenic mice expressing incomplete KATP LOF do reiterate mild hyperinsulinism, KATP knockout animals do not exhibit persistent hyperinsulinism. We have shown that islet excitability and glucose homeostasis are regulated by identical KATP channels in zebrafish. SUR1 truncation mutation (K499X) was introduced into the abcc8 gene to explore the possibility of using zebrafish for modeling human HI...
December 31, 2022: Islets
#9
JOURNAL ARTICLE
Priscila C Albuquerque, Fabio Zicker, Bruna P Fonseca
The advancement of drug repurposing (DR) relies on scientific leadership and innovative institutions with access to knowledge. We performed a bibliometric and social network analysis (covering the period 2011-2020) to map the DR research trends and to identify innovation and knowledge leaders (IKLs). The indexing rate of DR publications has steadily increased. Major research areas included emerging viruses, cancer, methodological approaches, preclinical research, and infectious diseases. Government and academia accounted for nearly 65% of funding...
December 2022: Drug Discovery Today
#10
JOURNAL ARTICLE
Kushal Sharma, Kwon Woo Kang, Young-Woo Seo, Elisabeth Glowatzki, Eunyoung Yi
Cochlear afferent nerve fibers (ANF) are the first neurons in the ascending auditory pathway. We investigated the low-voltage activating K+ channels expressed in ANF dendrites using isolated rat cochlear segments. Whole cell patch clamp recordings were made from the dendritic terminals of ANFs. Outward currents activating at membrane potentials as low as -64 mV were observed in all dendrites studied. These currents were inhibited by 4-aminopyridine (4-AP), a blocker known to preferentially inhibit low-voltage activating K+ currents (IKL ) in CNS auditory neurons and spiral ganglion neurons...
August 31, 2022: Experimental Neurobiology
#11
JOURNAL ARTICLE
Soma S Singareddy, Helen I Roessler, Conor McClenaghan, Jen Ikle, Rob Tryon, Gijs van Haaften, Colin G Nichols
KEY POINTS: Zebrafish cardiac myocytes (CM) and vascular smooth muscle (VSM) express functional KATP channels of similar subunit composition, structure, and metabolic sensitivity to their mammalian counterparts. In contrast to mammalian cardiovascular KATP channels, zebrafish channels are insensitive to potassium channel opener drugs (pinacidil, minoxidil) in both chambers of the heart and in VSM. We provide a first characterization of the molecular properties of fish KATP channels and validate the use of such genetically modified fish as models of human Cantú Syndrome and ABCC9-related Intellectual disability and Myopathy Syndrome...
November 24, 2021: Journal of Physiology
#12
JOURNAL ARTICLE
Jennifer M Iklé, Lawrence S Prince, David M Maahs
No abstract text is available yet for this article.
August 2021: Journal of Pediatrics
#13
REVIEW
Jennifer M Ikle, Anna L Gloyn
Since the discovery of insulin 100 years ago, our knowledge and understanding of diabetes have grown exponentially. Specifically, with regards to the genetics underlying diabetes risk, our discoveries have paralleled developments in our understanding of the human genome and our ability to study genomics at scale; these advancements in genetics have both accompanied and led to those in diabetes treatment. This review will explore the timeline and history of gene discovery and how this has coincided with progress in the fields of genomics...
July 22, 2021: Journal of Endocrinology
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JOURNAL ARTICLE
Yuan-Yuan Jia, Yue Yu, Hong-Jun Li
Periostin (POSTN) is an extracellular matrix (ECM) protein, involved in various diseases. This research focused on the detailed mechanisms study of periostin (POSTN) overexpression in renal cell carcinoma (RCC) invasion and migration. Western blot and RT-PCR were performed to explore POSTN expression in various RCC cells. Cells were transfected with siRNAs or lentivirus to regulate the expression of POSTN. The effects of POSTN on cell viability, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT) of RCC cells were determined by CCK-8, flow cytometry, migration and invasion assay and Western blot analysis...
2021: Journal of Cancer
#15
JOURNAL ARTICLE
Jennifer M Iklé, David M Maahs
No abstract text is available yet for this article.
June 2021: Journal of Pediatrics
#16
JOURNAL ARTICLE
Thangamani Muthukumar, Kemal M Akat, Hua Yang, Joseph E Schwartz, Carol Li, Heejung Bang, Iddo Z Ben-Dov, John R Lee, David Ikle, Anthony J Demetris, Thomas Tuschl, Manikkam Suthanthiran
BACKGROUND: Acute rejection (AR) and recurrent HCV (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management. METHODS: We performed small RNA sequencing and miRNA microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized RT-qPCR assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients...
May 11, 2021: Transplantation
#17
JOURNAL ARTICLE
Tima Dehghani, Phung N Thai, Harkanwalpreet Sodhi, Lu Ren, Padmini Sirish, Carol E Nader, Valeriy Timofeyev, James L Overton, Xiaocen Li, Kit S Lam, Nipavan Chiamvimonvat, Alyssa Panitch
AIMS: One of the hallmarks of myocardial infarction (MI) is excessive inflammation. During an inflammatory insult, damaged endothelial cells shed their glycocalyx, a carbohydrate-rich layer on the cell surface which provides a regulatory interface to immune cell adhesion. Selectin-mediated neutrophilia occurs as a result of endothelial injury and inflammation. We recently designed a novel selectin-targeting glycocalyx mimetic (termed DS-IkL) capable of binding inflamed endothelial cells...
January 7, 2022: Cardiovascular Research
#18
MULTICENTER STUDY
Sandy Feng, John C Bucuvalas, George V Mazariegos, John C Magee, Alberto Sanchez-Fueyo, Katharine M Spain, Andrew Lesniak, Sai Kanaparthi, Emily Perito, Veena L Venkat, Bryna E Burrell, Estella M Alonso, Nancy D Bridges, Edward Doo, Nitika A Gupta, Ryan W Himes, David Ikle, Annette M Jackson, Steven J Lobritto, Juan Jose Lozano, Mercedes Martinez, Vicky L Ng, Elizabeth B Rand, Averell H Sherker, Shikha S Sundaram, Yumirle P Turmelle, Michele Wood-Trageser, Anthony J Demetris
BACKGROUND AND AIMS: Tolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance. APPROACH AND RESULTS: We conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48 weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3-4)...
May 2021: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
#19
JOURNAL ARTICLE
Adnan Kefal, Erkan Oterkus
Shape sensing is one of most crucial components of typical structural health monitoring systems and has become a promising technology for future large-scale engineering structures to achieve significant improvement in their safety, reliability, and affordability. The inverse finite element method (iFEM) is an innovative shape-sensing technique that was introduced to perform three-dimensional displacement reconstruction of structures using in situ surface strain measurements. Moreover, isogeometric analysis (IGA) presents smooth function spaces such as non-uniform rational basis splines (NURBS), to numerically solve a number of engineering problems, and recently received a great deal of attention from both academy and industry...
May 8, 2020: Sensors
#20
JOURNAL ARTICLE
Peter G Stock, Roslyn B Mannon, Brian Armstrong, Natasha Watson, David Ikle, Mark Robien, Yvonne Morrison, Jon Odorico, Jonathan Fridell, Aneesh K Mehta, Kenneth A Newell
In a phase 2 multi-center open label randomized trial sponsored by the National Institutes of Health, simultaneous pancreas-kidney (SPK) recipients were randomized to a calcineurin inhibitor (CNI) based immunosuppressive regimen (tacrolimus) (n=21) or an investigational arm using low-dose CNI plus co-stimulation blockade (belatacept) with intended CNI withdrawal (n=22). Both arms included induction therapy with rabbit ATG, mycophenolate sodium or mycophenolate mofetil, and rapid withdrawal of steroids. Enrollment and CNI withdrawal were stopped after 43/60 planned subjects had been enrolled...
February 10, 2020: American Journal of Transplantation
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