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1. Eco-friendly synthesis of silver nanoparticles from peel and juice C. limon and their antiviral efficacy against HSV-1 and SARS-CoV-2

Author

Federica Dell'Annunziata, Ekaterine Mosidze, Veronica Folliero, Erwin P. Lamparelli, Valentina Lopardo, Pasquale Pagliano, Giovanna Della Porta, Massimiliano Galdiero, Aliosha Dzh Bakuridze, and Gianluigi Franci

Subjects
Nanotechnology, Silver nanoparticles (AgNPs), Antiviral activity, HSV-1, SARS-CoV-2, Green synthesis, Biomedical applications, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract

The growing threat of viral infections requires innovative therapeutic approaches to safeguard human health. Nanomaterials emerge as a promising solution to overcome the limitations associated with conventional therapies. The eco-friendly synthesis of silver nanoparticles (AgNPs) currently represents a method that guarantees antimicrobial efficacy, safety, and cost-effectiveness. This study explores the use of AgNPs derived from the peel (Lp-AgNPs) and juice (Lj-AgNPs) Citrus limon “Ovale di Sorrento”, cultivars of the Campania region. The antiviral potential was tested against viruses belonging to the Coronaviridae and Herpesviridae. AgNPs were synthesized by reduction method using silver nitrate solution mixed with aqueous extract of C. limon peel and juice. The formation of Lp-AgNPs and Lj-AgNPs was assessed using a UV–Vis spectrophotometer. The size, ζ-potential, concentration, and morphology of AgNPs were evaluated by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and field emission-scanning electron microscopy (FE-SEM). Cytotoxicity was evaluated in a concentration range between 500 and 7.8 µg/mL on VERO-76 and HaCaT cells, with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium test bromide (MTT). Antiviral activity consisted of virus pre-treatment, co-treatment, cellular pre-treatment, and post-infection tests versus HSV-1 and SARS-CoV-2 at a multiplicity of infections (MOI) of 0.01. Plaque reduction assays and real-time PCR provided data on the antiviral potential of tested compounds. Lp-AgNPs and Lj-AgNPs exhibited spherical morphology with respective diameters of 60 and 92 nm with concentrations of 4.22 and 4.84 × 1010 particles/mL, respectively. The MTT data demonstrated minimal cytotoxicity, with 50 % cytotoxic concentrations (CC50) of Lp-AgNPs and Lj-AgNPs against VERO cells of 754.6 and 486.7 µg/mL. Similarly, CC50 values against HaCaT were 457.3 µg/mL for Lp-AgNPs and 339.6 µg/mL for Lj-AgNPs, respectively. In the virus pre-treatment assay, 90 % inhibitory concentrations of HSV-1 and SARS-CoV-2 were 8.54–135.04 µg/mL for Lp-AgNPs and 6.13–186.77 µg/mL for Lj-AgNPs, respectively. The molecular investigation confirmed the antiviral data, recording a reduction in the UL54 and UL27 genes for HSV-1 and in the Spike (S) gene for SARS-CoV-2, following AgNP exposure. The results of this study suggest that Lp-AgNPs and Lj-AgNPs derived from C. Limon could offer a valid ecological, natural, local and safe strategy against viral infections.

Published
2024
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2. Genetic insights into resting heart rate and its role in cardiovascular disease

Author

Yordi J. van de Vegte, Ruben N. Eppinga, M. Yldau van der Ende, Yanick P. Hagemeijer, Yuvaraj Mahendran, Elias Salfati, Albert V. Smith, Vanessa Y. Tan, Dan E. Arking, Ioanna Ntalla, Emil V. Appel, Claudia Schurmann, Jennifer A. Brody, Rico Rueedi, Ozren Polasek, Gardar Sveinbjornsson, Cecile Lecoeur, Claes Ladenvall, Jing Hua Zhao, Aaron Isaacs, Lihua Wang, Jian’an Luan, Shih-Jen Hwang, Nina Mononen, Kirsi Auro, Anne U. Jackson, Lawrence F. Bielak, Linyao Zeng, Nabi Shah, Maria Nethander, Archie Campbell, Tuomo Rankinen, Sonali Pechlivanis, Lu Qi, Wei Zhao, Federica Rizzi, Toshiko Tanaka, Antonietta Robino, Massimiliano Cocca, Leslie Lange, Martina Müller-Nurasyid, Carolina Roselli, Weihua Zhang, Marcus E. Kleber, Xiuqing Guo, Henry J. Lin, Francesca Pavani, Tessel E. Galesloot, Raymond Noordam, Yuri Milaneschi, Katharina E. Schraut, Marcel den Hoed, Frauke Degenhardt, Stella Trompet, Marten E. van den Berg, Giorgio Pistis, Yih-Chung Tham, Stefan Weiss, Xueling S. Sim, Hengtong L. Li, Peter J. van der Most, Ilja M. Nolte, Leo-Pekka Lyytikäinen, M. Abdullah Said, Daniel R. Witte, Carlos Iribarren, Lenore Launer, Susan M. Ring, Paul S. de Vries, Peter Sever, Allan Linneberg, Erwin P. Bottinger, Sandosh Padmanabhan, Bruce M. Psaty, Nona Sotoodehnia, Ivana Kolcic, The DCCT/EDIC Research Group, David O. Arnar, Daniel F. Gudbjartsson, Hilma Holm, Beverley Balkau, Claudia T. Silva, Christopher H. Newton-Cheh, Kjell Nikus, Perttu Salo, Karen L. Mohlke, Patricia A. Peyser, Heribert Schunkert, Mattias Lorentzon, Jari Lahti, Dabeeru C. Rao, Marilyn C. Cornelis, Jessica D. Faul, Jennifer A. Smith, Katarzyna Stolarz-Skrzypek, Stefania Bandinelli, Maria Pina Concas, Gianfranco Sinagra, Thomas Meitinger, Melanie Waldenberger, Moritz F. Sinner, Konstantin Strauch, Graciela E. Delgado, Kent D. Taylor, Jie Yao, Luisa Foco, Olle Melander, Jacqueline de Graaf, Renée de Mutsert, Eco J. C. de Geus, Åsa Johansson, Peter K. Joshi, Lars Lind, Andre Franke, Peter W. Macfarlane, Kirill V. Tarasov, Nicholas Tan, Stephan B. Felix, E-Shyong Tai, Debra Q. Quek, Harold Snieder, Johan Ormel, Martin Ingelsson, Cecilia Lindgren, Andrew P. Morris, Olli T. Raitakari, Torben Hansen, Themistocles Assimes, Vilmundur Gudnason, Nicholas J. Timpson, Alanna C. Morrison, Patricia B. Munroe, David P. Strachan, Niels Grarup, Ruth J. F. Loos, Susan R. Heckbert, Peter Vollenweider, Caroline Hayward, Kari Stefansson, Philippe Froguel, Leif Groop, Nicholas J. Wareham, Cornelia M. van Duijn, Mary F. Feitosa, Christopher J. O’Donnell, Mika Kähönen, Markus Perola, Michael Boehnke, Sharon L. R. Kardia, Jeanette Erdmann, Colin N. A. Palmer, Claes Ohlsson, David J. Porteous, Johan G. Eriksson, Claude Bouchard, Susanne Moebus, Peter Kraft, David R. Weir, Daniele Cusi, Luigi Ferrucci, Sheila Ulivi, Giorgia Girotto, Adolfo Correa, Stefan Kääb, Annette Peters, John C. Chambers, Jaspal S. Kooner, Winfried März, Jerome I. Rotter, Andrew A. Hicks, J. Gustav Smith, Lambertus A. L. M. Kiemeney, Dennis O. Mook-Kanamori, Brenda W. J. H. Penninx, Ulf Gyllensten, James F. Wilson, Stephen Burgess, Johan Sundström, Wolfgang Lieb, J. Wouter Jukema, Mark Eijgelsheim, Edward L. M. Lakatta, Ching-Yu Cheng, Marcus Dörr, Tien-Yin Wong, Charumathi Sabanayagam, Albertine J. Oldehinkel, Harriette Riese, Terho Lehtimäki, Niek Verweij, and Pim van der Harst

Subjects
Science
Abstract

Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Published
2023
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3. Biomimetic proteolipid vesicles for reverting GPI deficiency in paroxysmal nocturnal hemoglobinuria

Author

Valentina Giudice, Pasqualina Scala, Erwin P. Lamparelli, Marisa Gorrese, Bianca Serio, Angela Bertolini, Francesca Picone, Giovanna Della Porta, and Carmine Selleri

Subjects
Drug delivery system, Natural sciences, Biological sciences, Biochemistry, Biomolecules, Science
Abstract

Summary: Nano-vesicular carriers are promising tissue-specific drug delivery platforms. Here, biomimetic proteolipid vesicles (BPLVs) were used for delivery of glycosylphosphatidylinositol (GPI)-anchored proteins to GPI deficient paroxysmal nocturnal hemoglobinuria (PNH) cells. BPLVs were assembled as single unilamellar monodispersed (polydispersity index, 0.1) negatively charged (ζ-potential, −28.6 ± 5.6 mV) system using microfluidic technique equipped with Y-shaped chip. GPI-anchored and not-GPI proteins on BPLV surface were detected by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy and PNH subjects were treated with BPLVs (final concentration, 0.5 mg/mL), and cells displayed an excellent protein uptake, documented by flow cytometry immunophenotyping and confocal microscopy. BPLV-treated cells stressed with complement components showed an increased resistance to complement-mediated lysis, both healthy and PNH PBMCs. In conclusion, BPLVs could be effective nanocarriers for protein transfer to targeted cells to revert protein deficiency, like in PNH disease. However, further in vivo studies are required to validate our preclinical in vitro results.

Published
2024
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4. Enhancing Seed Germination Test Classification for Pole Sitao (Vigna unguiculata (L.) Walp.) Using SSD MobileNet and Faster R-CNN Models

Author

Mariel John B. Brutas, Arthur L. Fajardo, Erwin P. Quilloy, Luther John R. Manuel, and Adrian A. Borja

Subjects
pole sitao seed germination, machine learning in agriculture, seed germination classification, germination test automation, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

The classification of germinated pole sitao (Vigna unguiculata (L.) Walp.) seeds is important in seed germination tests. The automation of this process has been explored for different grain and legume seeds but is only limited to binary classification. This study aimed to develop a classifier system that can recognize three classes: normal, abnormal, and ungerminated. SSD MobileNet and Faster R-CNN models were trained to perform the classification. Both were trained using 1500 images of germinated seeds at fifth- and eighth-day observations. Each class had 500 images. The trained models were evaluated using 150 images per class. The SSD MobileNet model had an accuracy of 0.79 while the Faster R-CNN model had an accuracy of 0.75. The results showed that the average accuracies for the classes were significantly different from one another based on one-way ANOVA at a 95% confidence level with an F-critical value of 3.0159. The SSD MobileNet model outperformed the Faster R-CNN model in classifying pole sitao seeds, with improved precision in identifying abnormal and ungerminated seeds on the fifth day and normal and ungerminated seeds on the eighth day. The results confirm the potential of the SSD MobileNet model as a more reliable classifier in germination tests.

Published
2024
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5. Mendelian randomization indicates causal effects of estradiol levels on kidney function in males

Author

M. Kamal Nasr, Claudia Schurmann, Erwin P. Böttinger, and Alexander Teumer

Subjects
glomerular filtration rate, steroids, albuminuria, genome-wide association study, causality, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

ContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.ObjectiveWe conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.DesignWe performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men (n = 206,927) and women (n = 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR, n = 567,460), urine albumin-to-creatinine ratio (UACR, n = 547,361), and CKD (n = 41,395 cases and n = 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data (n = 11,798 men and n = 6,835 women) to identify novel genetic associations with levels of estradiol, and then used these variants as instruments in a one-sample MR.ResultsThe two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077; p = 5.2E-05). We identified a single locus at chromosome 14 associated with estradiol levels in men being significant in the one-sample MR on eGFR (beta = 0.199; p = 0.017). We revealed significant results with eGFR in postmenopausal women and with UACR in premenopausal women, which did not reach statistical significance in the sensitivity MR analyses. No causal effect of eGFR or UACR on estradiol levels was found.ConclusionsWe conclude that serum estradiol levels may have a causal effect on kidney function. Our MR results provide starting points for studies to develop therapeutic strategies to reduce kidney disease.

Published
2023
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6. Polyethylene glycol-induced drought stress screening of selected Philippine high-yielding sugarcane varieties

Author

Jose Arnel O. Reyes, Denzel E. Casas, Jayson L. Gandia, Milkie Joy L. Parducho, Eunice M. Renovalles, Erwin P. Quilloy, and Evelyn F. Delfin

Subjects
Chlorophyll fluorescence, Drought, Polyethylene glycol, Rapid screening, Sugarcane, Agriculture (General), S1-972, Nutrition. Foods and food supply, TX341-641
Abstract

A greenhouse study was conducted to characterize the drought response of eight high-yielding sugarcane varieties at tillering stage using polyethylene glycol 6000 (PEG6000) induced drought conditions. Plant height, stalk diameter, dry matter accumulation, root characteristics, stomatal conductance, chlorophyll fluorescence, SPAD, normalized difference vegetation index (NDVI), and canopy temperature were evaluated at 2.5 months after planting after four weeks of induced drought conditions. The study aimed to determine whether 1.0% PEG treatment would be able to produce significant differences among test genotypes and use it as a basis to determine drought-tolerant and susceptible varieties. Significant differences were observed among genotypes in PEG stress treatments. PEG stress resulted in significant reductions relative to non-PEG treatment in plant height (32.1%), leaf dry matter (31.6%), and stalk dry matter (49.5%) while total root length (11.8%), root surface area (7.8%) and root volume (19.6%) have generally increased. Reduced plant height, stalk diameter, and dry matter accumulation were observed in susceptible genotypes, while potential tolerant lines maintained or exhibited less reduction in these traits. Moreover, principal component analysis suggests that stalk dry matter, stomatal conductance, chlorophyll fluorescence plant height, SPAD, canopy temperature, and NDVI, highly contributed to the overall variation in the data (41.5%). With this, vars. 2289, 1011, 2569, and 1899 were identified to be potential drought-tolerant varieties while vars. 1763 and 2155 were potential drought susceptible varieties. Screening for drought tolerance under controlled conditions using PEG-induced drought stress offers a promising approach for sugarcane breeding especially when focusing on specific drought responses during important formative stages such as tillering stage. Being able to select genotypes of interest as early as the tillering stage would significantly hasten breeding cycles and will highly benefit the efforts towards drought stress tolerance in sugarcane.

Published
2023
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7. Implementation and evaluation of personal genetic testing as part of genomics analysis courses in German universities

Author

Tamara Slosarek, Susanne Ibing, Barbara Schormair, Henrike O. Heyne, Erwin P. Böttinger, Till F. M. Andlauer, and Claudia Schurmann

Subjects
Genomics education, Personal genotyping, Personalized medicine, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Purpose Due to the increasing application of genome analysis and interpretation in medical disciplines, professionals require adequate education. Here, we present the implementation of personal genotyping as an educational tool in two genomics courses targeting Digital Health students at the Hasso Plattner Institute (HPI) and medical students at the Technical University of Munich (TUM). Methods We compared and evaluated the courses and the students’ perceptions on the course setup using questionnaires. Results During the course, students changed their attitudes towards genotyping (HPI: 79% [15 of 19], TUM: 47% [25 of 53]). Predominantly, students became more critical of personal genotyping (HPI: 73% [11 of 15], TUM: 72% [18 of 25]) and most students stated that genetic analyses should not be allowed without genetic counseling (HPI: 79% [15 of 19], TUM: 70% [37 of 53]). Students found the personal genotyping component useful (HPI: 89% [17 of 19], TUM: 92% [49 of 53]) and recommended its inclusion in future courses (HPI: 95% [18 of 19], TUM: 98% [52 of 53]). Conclusion Students perceived the personal genotyping component as valuable in the described genomics courses. The implementation described here can serve as an example for future courses in Europe.

Published
2023
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8. Conservative Treatment of Ulnar Nerve Compression at the Elbow: A Systematic Review and Meta-Analysis

Author

Tinatin Natroshvili, Milly S. van de Warenburg, Erwin P. Heine, Nicholas J. Slater, Erik T. Walbeehm, and Ronald H. M. A. Bartels

Subjects
ulnar nerve compression syndromes, nerve compression syndromes, conservative treatment, Surgery, RD1-811
Abstract

Background The clinical results of conservative treatment options for ulnar compression at the elbow have not been clearly determined. The aim of this review was to evaluate available conservative treatment options and their effectiveness for ulnar nerve compression at the elbow. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a systematic review and meta-analysis of studies was performed. Literature search was performed using Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Results Of the 1,079 retrieved studies, 20 were eligible for analysis and included 687 cases of ulnar neuropathy at the elbow. Improvement of symptoms was reported in 54% of the cases receiving a steroid/lidocaine injection (95% confidence interval [CI], 41–67) and in 89% of the cases using a splint device (95% CI, 69–99). Conclusions Conservative management seems to be effective. Both lidocaine/steroid injections and splint devices gave a statistically significant improvement of symptoms and are suitable options for patients who refuse an operative procedure or need a bridge to their surgery. Splinting is preferred over injections, as it shows a higher rate of improvement.

Published
2023
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9. Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization [version 1; peer review: 2 approved]

Author

Natasha H. J. Ng, Sara M. Willems, Jian'an Luan, Rebecca S. Fine, Juan Fernandez, Jennifer Wessel, Eleanor Wheeler, Gaelle Marenne, Hidetoshi Kitajima, Hanieh Yaghootkar, Xueling Sim, Ian J. Deary, Sai Chen, Shuai Wang, Yii-Der Ida Chen, Caroline Hayward, Yuning Chen, Jennifer L. Asimit, Claudia Langenberg, Tibor V. Varga, Archie Campbell, Rona J. Strawbridge, Shuang Feng, Tarunveer S. Ahluwalia, Erica L. Kleinbrink, Emil V. Appel, Ping An, Lawrence F. Bielak, Dan E. Arking, Jennifer A. Brody, Nathan A. Bihlmeyer, David Porteous, Ayse Demirkan, Audrey Y. Chu, Franco Giulianini, James S. Floyd, Stefan Gustafsson, Xiuqing Guo, Johanna Jakobsdottir, Anne U. Jackson, Stavroula Kanoni, Richard A. Jensen, Igor Rudan, Man Li, Sirkka Keinanen-Kiukaanniemi, Alisa K. Manning, Yingchang Lu, Karina Meidtner, Jonathan Marten, Giorgio Pistis, Taulant Muka, Kenneth M. Rice, Bram Prins, Albert Vernon Smith, Serena Sanna, Lorraine Southam, Jennifer A. Smith, Vinicius Tragante, Heather M. Stringham, Helen R. Warren, Sander W. van der Laan, Andrianos M. Yiorkas, Jie Yao, Wei Zhao, Weihua Zhang, Heather M. Highland, Mariaelisa Graff, Eirini Marouli, Anne E. Justice, Wesam A. Alhejily, Saima Afaq, Folkert W. Asselbergs, Najaf Amin, Michiel L. Bots, Lori L. Bonnycastle, Ji Chen, Ivan Brandslund, Abbas Dehghan, John Danesh, Tapani Ebeling, Jessica D. Faul, Aliki-Eleni Farmaki, Steve Franks, Paul W. Franks, Anette P. Gjesing, Andreas Fritsche, Göran Hallmans, Mark O. Goodarzi, Karl-Heinz Herzig, Tamara B. Harris, Min A Jhun, Marie-France Hivert, Marit E. Jørgensen, Torben Jørgensen, Eero Kajantie, Pekka Jousilahti, Sharon L.R. Kardia, Maria Karaleftheri, Heikki A. Koistinen, Leena Kinnunen, Peter Kovacs, Pirjo Komulainen, Markku Laakso, Johanna Kuusisto, Aaron Leong, Lenore J. Launer, Jocelyn E. Manning Fox, Jaana Lindström, Nisa M. Maruthur, Satu Männistö, Antonella Mulas, Leena Moilanen, Matthew Neville, Mike A. Nalls, Alison Pattie, James S. Pankow, Hannu Puolijoki, Eva R.B. Petersen, Paul Redmond, Asif Rasheed, Michael Roden, Frida Renström, Juha Saltevo, Danish Saleheen, Sylvain Sebert, Kai Savonen, Alena Stančáková, Kerrin S. Small, Konstantin Strauch, Jakob Stokholm, Betina H. Thuesen, Juha Auvinen, E-Shyong Tai, Emmanouil Tsafantakis, Anke Tönjes, Jaakko Tuomilehto, Tiinamaija Tuomi, Marja Vääräsmäki, Matti Uusitupa, Magdalena Zoledziewska, Ilonca Vaartjes, Beverley Balkau, Goncalo Abecasis, Alexandra I. Blakemore, Hans Bisgaard, Heiner Boeing, Ruth J.F. Loos, Matthias Blüher, Klaus Bønnelykke, Eric Boerwinkle, Mark J. Caulfield, Erwin P. Bottinger, Daniel I. Chasman, John C. Chambers, Francis S. Collins, Ching-Yu Cheng, Francesco Cucca, Josef Coresh, George Dedoussis, Gert J. de Borst, Hester M. den Ruijter, Panos Deloukas, Ele Ferrannini, Michele K. Evans, Harald Grallert, Oscar H. Franco, Arfan Ikram, Joel N. Hirschhorn, Fredrik Karpe, Erik Ingelsson, Wieland Kiess, Carolina Medina-Gomez, Kay-Tee Kaw, Antje Körner, Jaspal S. Kooner, Cecilia M. Lindgren, Timo Lakka, Ching-Ti Liu, Leonard Lipovich, Patrick E. MacDonald, Jun Liu, Andrew D. Morris, Karen L. Mohlke, Alison Murray, Patricia B. Munroe, Gerard Pasterkamp, Colin N. A . Palmer, Patricia A. Peyser, Oluf Pedersen, Paul M. Ridker, Rainer Rauramaa, Patrik Rorsman, Olov Rolandsson, Veikko Salomaa, Frits R. Rosendaal, Robert Sladek, Matthias B. Schulze, Michael Stumvoll, Timothy D. Spector, Mark Walker, Cornelia M. van Duijn, David R. Weir, Nick J. Wareham, Tien Yin Wong, James G. Wilson, Alan B. Zonderman, Eleftheria Zeggini, Andrew P. Morris, Jerome I. Rotter, Jose C. Florez, Michael Boehnke, James B. Meigs, Mark I. McCarthy, Robert A. Scott, Anubha Mahajan, Inês Barroso, Anna L. Gloyn, Michael A. Province, Niels Grarup, Ruifang Li-Gao, Jette Bork-Jensen, Yongmei Liu, Allan Linneberg, Leslie A. Lange, Sandosh Padmanabhan, Gail Davies, Lars Lind, Bruce M. Psaty, Tea Skaaby, Torben Hansen, Ozren Polasek, John M. Starr, Dennis O. Mook-Kanamori, Vilmundur Gudnason, Kent D. Taylor, Marjo-Riitta Järvelin, Renée de Mutsert, Paul Elliott, Josée Dupuis, Blair H. Smith, and Andrew T. Hattersley

Subjects
exome chip, glycaemic traits, genetic discovery, effector genes, summary statistics resources, eng, Medicine, Science
Abstract

Background Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. Methods To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. Results Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. Conclusions Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

Published
2023
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10. Rare Tumors Causing Median Nerve Compression in Adults—A Narrative Review

Author

Tinatin Natroshvili, Kirsten Peperkamp, Masoud A. Malyar, David Wijnberg, Erwin P. Heine, and Erik T. Walbeehm

Subjects
median neuropathy, neoplasms, rare diseases, Surgery, RD1-811
Abstract

The median nerve can be compressed due to a tumor along the course of the median nerve, causing typical compression symptoms or even persistence or recurrence after an operation. The aim of this review is to provide a comprehensive overview of rare tumors described in recent publications that cause median nerve compression and to evaluate treatment options. The PubMed, Embase, and Web of Science databases were searched for studies describing median nerve compression due to a tumor in adults, published from the year 2000 and written in English. From 94 studies, information of approximately 100 patients have been obtained. Results The rare tumors causing compression were in 32 patients located at the carpal tunnel, in 21 cases in the palm of the hand, and 28 proximal from the carpal tunnel. In the other cases the compression site extended over a longer trajectory. There were 37 different histological types of lesions. Complete resection of the tumor was possible in 58 cases. A total of 8 patients presented for the second time after receiving initial therapy. During follow-up, three cases of recurrence were reported with a mean follow-up period of 11 months. The most common published cause of median nerve compression is the lipofibromatous hamartoma. Besides the typical sensory and motor symptoms of median nerve compression, a thorough physical examination of the complete upper extremity is necessary to find any swelling or triggering that might raise suspicion of the presence of a tumor.

Published
2022
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11. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author

Thomas W. Winkler, Humaira Rasheed, Alexander Teumer, Mathias Gorski, Bryce X. Rowan, Kira J. Stanzick, Laurent F. Thomas, Adrienne Tin, Anselm Hoppmann, Audrey Y. Chu, Bamidele Tayo, Chris H. L. Thio, Daniele Cusi, Jin-Fang Chai, Karsten B. Sieber, Katrin Horn, Man Li, Markus Scholz, Massimiliano Cocca, Matthias Wuttke, Peter J. van der Most, Qiong Yang, Sahar Ghasemi, Teresa Nutile, Yong Li, Giulia Pontali, Felix Günther, Abbas Dehghan, Adolfo Correa, Afshin Parsa, Agnese Feresin, Aiko P. J. de Vries, Alan B. Zonderman, Albert V. Smith, Albertine J. Oldehinkel, Alessandro De Grandi, Alexander R. Rosenkranz, Andre Franke, Andrej Teren, Andres Metspalu, Andrew A. Hicks, Andrew P. Morris, Anke Tönjes, Anna Morgan, Anna I. Podgornaia, Annette Peters, Antje Körner, Anubha Mahajan, Archie Campbell, Barry I. Freedman, Beatrice Spedicati, Belen Ponte, Ben Schöttker, Ben Brumpton, Bernhard Banas, Bernhard K. Krämer, Bettina Jung, Bjørn Olav Åsvold, Blair H. Smith, Boting Ning, Brenda W. J. H. Penninx, Brett R. Vanderwerff, Bruce M. Psaty, Candace M. Kammerer, Carl D. Langefeld, Caroline Hayward, Cassandra N. Spracklen, Cassianne Robinson-Cohen, Catharina A. Hartman, Cecilia M. Lindgren, Chaolong Wang, Charumathi Sabanayagam, Chew-Kiat Heng, Chiara Lanzani, Chiea-Chuen Khor, Ching-Yu Cheng, Christian Fuchsberger, Christian Gieger, Christian M. Shaffer, Christina-Alexandra Schulz, Cristen J. Willer, Daniel I. Chasman, Daniel F. Gudbjartsson, Daniela Ruggiero, Daniela Toniolo, Darina Czamara, David J. Porteous, Dawn M. Waterworth, Deborah Mascalzoni, Dennis O. Mook-Kanamori, Dermot F. Reilly, E. Warwick Daw, Edith Hofer, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, E-Shyong Tai, Eulalia Catamo, Federica Rizzi, Feng Guo, Fernando Rivadeneira, Franco Guilianini, Gardar Sveinbjornsson, Georg Ehret, Gerard Waeber, Ginevra Biino, Giorgia Girotto, Giorgio Pistis, Girish N. Nadkarni, Graciela E. Delgado, Grant W. Montgomery, Harold Snieder, Harry Campbell, Harvey D. White, He Gao, Heather M. Stringham, Helena Schmidt, Hengtong Li, Hermann Brenner, Hilma Holm, Holgen Kirsten, Holly Kramer, Igor Rudan, Ilja M. Nolte, Ioanna Tzoulaki, Isleifur Olafsson, Jade Martins, James P. Cook, James F. Wilson, Jan Halbritter, Janine F. Felix, Jasmin Divers, Jaspal S. Kooner, Jeannette Jen-Mai Lee, Jeffrey O’Connell, Jerome I. Rotter, Jianjun Liu, Jie Xu, Joachim Thiery, Johan Ärnlöv, Johanna Kuusisto, Johanna Jakobsdottir, Johanne Tremblay, John C. Chambers, John B. Whitfield, John M. Gaziano, Jonathan Marten, Josef Coresh, Jost B. Jonas, Josyf C. Mychaleckyj, Kaare Christensen, Kai-Uwe Eckardt, Karen L. Mohlke, Karlhans Endlich, Katalin Dittrich, Kathleen A. Ryan, Kenneth M. Rice, Kent D. Taylor, Kevin Ho, Kjell Nikus, Koichi Matsuda, Konstantin Strauch, Kozeta Miliku, Kristian Hveem, Lars Lind, Lars Wallentin, Laura M. Yerges-Armstrong, Laura M. Raffield, Lawrence S. Phillips, Lenore J. Launer, Leo-Pekka Lyytikäinen, Leslie A. Lange, Lorena Citterio, Lucija Klaric, M. Arfan Ikram, Marcus Ising, Marcus E. Kleber, Margherita Francescatto, Maria Pina Concas, Marina Ciullo, Mario Piratsu, Marju Orho-Melander, Markku Laakso, Markus Loeffler, Markus Perola, Martin H. de Borst, Martin Gögele, Martina La Bianca, Mary Ann Lukas, Mary F. Feitosa, Mary L. Biggs, Mary K. Wojczynski, Maryam Kavousi, Masahiro Kanai, Masato Akiyama, Masayuki Yasuda, Matthias Nauck, Melanie Waldenberger, Miao-Li Chee, Miao-Ling Chee, Michael Boehnke, Michael H. Preuss, Michael Stumvoll, Michael A. Province, Michele K. Evans, Michelle L. O’Donoghue, Michiaki Kubo, Mika Kähönen, Mika Kastarinen, Mike A. Nalls, Mikko Kuokkanen, Mohsen Ghanbari, Murielle Bochud, Navya Shilpa Josyula, Nicholas G. Martin, Nicholas Y. Q. Tan, Nicholette D. Palmer, Nicola Pirastu, Nicole Schupf, Niek Verweij, Nina Hutri-Kähönen, Nina Mononen, Nisha Bansal, Olivier Devuyst, Olle Melander, Olli T. Raitakari, Ozren Polasek, Paolo Manunta, Paolo Gasparini, Pashupati P. Mishra, Patrick Sulem, Patrik K. E. Magnusson, Paul Elliott, Paul M. Ridker, Pavel Hamet, Per O. Svensson, Peter K. Joshi, Peter Kovacs, Peter P. Pramstaller, Peter Rossing, Peter Vollenweider, Pim van der Harst, Rajkumar Dorajoo, Ralene Z. H. Sim, Ralph Burkhardt, Ran Tao, Raymond Noordam, Reedik Mägi, Reinhold Schmidt, Renée de Mutsert, Rico Rueedi, Rob M. van Dam, Robert J. Carroll, Ron T. Gansevoort, Ruth J. F. Loos, Sala Cinzia Felicita, Sanaz Sedaghat, Sandosh Padmanabhan, Sandra Freitag-Wolf, Sarah A. Pendergrass, Sarah E. Graham, Scott D. Gordon, Shih-Jen Hwang, Shona M. Kerr, Simona Vaccargiu, Snehal B. Patil, Stein Hallan, Stephan J. L. Bakker, Su-Chi Lim, Susanne Lucae, Suzanne Vogelezang, Sven Bergmann, Tanguy Corre, Tarunveer S. Ahluwalia, Terho Lehtimäki, Thibaud S. Boutin, Thomas Meitinger, Tien-Yin Wong, Tobias Bergler, Ton J. Rabelink, Tõnu Esko, Toomas Haller, Unnur Thorsteinsdottir, Uwe Völker, Valencia Hui Xian Foo, Veikko Salomaa, Veronique Vitart, Vilmantas Giedraitis, Vilmundur Gudnason, Vincent W. V. Jaddoe, Wei Huang, Weihua Zhang, Wen Bin Wei, Wieland Kiess, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Xin Gao, Xueling Sim, Ya Xing Wang, Yechiel Friedlander, Yih-Chung Tham, Yoichiro Kamatani, Yukinori Okada, Yuri Milaneschi, Zhi Yu, Lifelines cohort study, DiscovEHR/MyCode study, VA Million Veteran Program, Klaus J. Stark, Kari Stefansson, Carsten A. Böger, Adriana M. Hung, Florian Kronenberg, Anna Köttgen, Cristian Pattaro, and Iris M. Heid

Subjects
Biology (General), QH301-705.5
Abstract

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.

Published
2022
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12. State Financial Incentives for Work-Based Learning. Policy Brief

Author

Education Commission of the States (ECS), Tom Keily, and Ben Erwin

Abstract

High-quality work-based learning opportunities enable students to develop necessary skills and contribute to positive employment outcomes. State leaders are recognizing the value of work-based learning experiences -- not only for individuals but in service of state attainment and workforce development goals. As leaders recognize the value, financial incentives can help offset costs associated with offering, engaging in and supporting work-based learning and serve as one tool to address barriers to access and expansion of work-based learning. Informed by a 50-state policy scan, this Policy Brief highlights key elements of financial incentives in state policy for each group: students, employers, and education institutions and intermediaries. Each section is informed by a 50-state policy scan and state examples are included throughout.

Published
2024

13. Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition

Author

Rebecca Rimbach, Yosuke Yamada, Hiroyuki Sagayama, Philip N. Ainslie, Lene F. Anderson, Liam J. Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E. Blaak, Stephane Blanc, Alberto G. Bonomi, Carlijn V. C. Bouten, Pascal Bovet, Maciej S. Buchowski, Nancy F. Butte, Stefan G. J. A. Camps, Graeme L. Close, Jamie A. Cooper, Sai Krupa Das, Lara R. Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W. Fudge, Annelies H. Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B. Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M. Joosen, Peter Katzmarzyk, Kitty P. Kempen, Misaka Kimura, William E. Kraus, Robert F. Kushner, Estelle V. Lambert, William R. Leonard, Nader Lessan, Corby K. Martin, Anine C. Medin, Erwin P. Meijer, James C. Morehen, James P. Morton, Marian L. Neuhouser, Theresa A. Nicklas, Robert M. Ojiambo, Kirsi H. Pietiläinen, Yannis P. Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L. Prentice, Roberto A. Rabinovich, Susan B. Racette, David A. Raichlen, Eric Ravussin, Rebecca M. Reynolds, Susan B. Roberts, Albertine J. Schuit, Anders M. Sjödin, Eric Stice, Samuel S. Urlacher, Giulio Valenti, Ludo M. Van Etten, Edgar A. Van Mil, Jonathan C. K. Wells, George Wilson, Brian M. Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J. Murphy-Alford, Cornelia U. Loechl, Amy H. Luke, Jennifer Rood, Dale A. Schoeller, Klaas R. Westerterp, William W. Wong, John R. Speakman, Herman Pontzer, and The IAEA DLW Database Consortium

Subjects
Science
Abstract

Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.

Published
2022
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14. Lessons on Expanding Quality CTE and Work-Based Learning. Policy Brief

Author

Education Commission of the States (ECS), Tom Keily, Ben Erwin, and Lauren Peisach

Abstract

High-quality career and technical education (CTE) and work-based learning opportunities can support students along a pathway to credential attainment, employment and upward economic mobility through intentional skill development and experiential learning. CTE concentration in high school can increase graduation rates while helping students build employability skills that can support positive outcomes in the workforce. When CTE concentration is paired with opportunities for postsecondary credit or a quality work-based learning experience, students are more likely to attain postsecondary and workforce credentials, successfully enter the workforce and earn higher wages. The Education Commission of the States staff members interviewed state leaders and policymakers, including state education agency staff, state workforce development agency staff, higher education agency staff and district leaders in Delaware, Iowa, Maryland, North Dakota, South Carolina and Washington to better understand how they align CTE and work-based learning policies and programs with workforce needs. This Policy Brief highlights key findings from the interviews, including insight into obstacles and promising practices in increasing student access, program quality and stakeholder engagement.

Published
2024

15. Human total, basal and activity energy expenditures are independent of ambient environmental temperature

Author

Xueying Zhang, Yosuke Yamada, Hiroyuki Sagayama, Philip N. Ainslie, Ellen E. Blaak, Maciej S. Buchowski, Graeme L. Close, Jamie A. Cooper, Sai Krupa Das, Lara R. Dugas, Michael Gurven, Asmaa El Hamdouchi, Sumei Hu, Noorjehan Joonas, Peter Katzmarzyk, William E. Kraus, Robert F. Kushner, William R. Leonard, Corby K. Martin, Erwin P. Meijer, Marian L. Neuhouser, Robert M. Ojiambo, Yannis P. Pitsiladis, Guy Plasqui, Ross L. Prentice, Susan B. Racette, Eric Ravussin, Leanne M. Redman, Rebecca M. Reynolds, Susan B. Roberts, Luis B. Sardinha, Analiza M. Silva, Eric Stice, Samuel S. Urlacher, Edgar A. Van Mil, Brian M. Wood, Alexia J. Murphy-Alford, Cornelia Loechl, Amy H. Luke, Jennifer Rood, Dale A. Schoeller, Klaas R. Westerterp, William W. Wong, Herman Pontzer, John R. Speakman, Lene F. Andersen, Liam J. Anderson, Lenore Arab, Issad Baddou, Bedu Addo, Stephane Blanc, Alberto Bonomi, Carlijn V.C. Bouten, Pascal Bovet, Stefan Branth, Niels C. De Bruin, Nancy F. Butte, Lisa H. Colbert, Stephan G. Camps, Alice E. Dutman, Simon D. Eaton, Ulf Ekelund, Sonja Entringer, Cara Ebbeling, Sölve Elmståhl, Mikael Fogelholm, Terrence Forrester, Barry W. Fudge, Tamara Harris, Rik Heijligenberg, Annelies H. Goris, Catherine Hambly, Marije B. Hoos, Hans U. Jorgensen, Annemiek M. Joosen, Kitty P. Kempen, Misaka Kimura, Watanee Kriengsinyos, Estelle V. Lambert, Christel L. Larsson, Nader Lessan, David S. Ludwig, Margaret McCloskey, Anine C. Medin, Gerwin A. Meijer, Eric Matsiko, Alida Melse-Boonstra, James C. Morehen, James P. Morton, Theresa A. Nicklas, Daphne L. Pannemans, Kirsi H. Pietiläinen, Renaat M. Philippaerts, Roberto A. Rabinovich, John J. Reilly, Elisabet M. Rothenberg, Albertine J. Schuit, Sabine Schulz, Anders M. Sjödin, Amy Subar, Minna Tanskanen, Ricardo Uauy, Giulio Valenti, Ludo M. Van Etten, Rita Van den Berg-Emons, Wim G. Van Gemert, Erica J. Velthuis-te Wierik, Wilhelmine W. Verboeket-van de Venne, Jeanine A. Verbunt, Jonathan C.K. Wells, and George Wilson

Subjects
Human activity in medical context, Human Physiology, Human metabolism, Science
Abstract

Summary: Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p

Published
2022
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17. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author

Ioanna Ntalla, Lu-Chen Weng, James H. Cartwright, Amelia Weber Hall, Gardar Sveinbjornsson, Nathan R. Tucker, Seung Hoan Choi, Mark D. Chaffin, Carolina Roselli, Michael R. Barnes, Borbala Mifsud, Helen R. Warren, Caroline Hayward, Jonathan Marten, James J. Cranley, Maria Pina Concas, Paolo Gasparini, Thibaud Boutin, Ivana Kolcic, Ozren Polasek, Igor Rudan, Nathalia M. Araujo, Maria Fernanda Lima-Costa, Antonio Luiz P. Ribeiro, Renan P. Souza, Eduardo Tarazona-Santos, Vilmantas Giedraitis, Erik Ingelsson, Anubha Mahajan, Andrew P. Morris, Fabiola Del Greco M, Luisa Foco, Martin Gögele, Andrew A. Hicks, James P. Cook, Lars Lind, Cecilia M. Lindgren, Johan Sundström, Christopher P. Nelson, Muhammad B. Riaz, Nilesh J. Samani, Gianfranco Sinagra, Sheila Ulivi, Mika Kähönen, Pashupati P. Mishra, Nina Mononen, Kjell Nikus, Mark J. Caulfield, Anna Dominiczak, Sandosh Padmanabhan, May E. Montasser, Jeff R. O’Connell, Kathleen Ryan, Alan R. Shuldiner, Stefanie Aeschbacher, David Conen, Lorenz Risch, Sébastien Thériault, Nina Hutri-Kähönen, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Olli T. Raitakari, Catriona L. K. Barnes, Harry Campbell, Peter K. Joshi, James F. Wilson, Aaron Isaacs, Jan A. Kors, Cornelia M. van Duijn, Paul L. Huang, Vilmundur Gudnason, Tamara B. Harris, Lenore J. Launer, Albert V. Smith, Erwin P. Bottinger, Ruth J. F. Loos, Girish N. Nadkarni, Michael H. Preuss, Adolfo Correa, Hao Mei, James Wilson, Thomas Meitinger, Martina Müller-Nurasyid, Annette Peters, Melanie Waldenberger, Massimo Mangino, Timothy D. Spector, Michiel Rienstra, Yordi J. van de Vegte, Pim van der Harst, Niek Verweij, Stefan Kääb, Katharina Schramm, Moritz F. Sinner, Konstantin Strauch, Michael J. Cutler, Diane Fatkin, Barry London, Morten Olesen, Dan M. Roden, M. Benjamin Shoemaker, J. Gustav Smith, Mary L. Biggs, Joshua C. Bis, Jennifer A. Brody, Bruce M. Psaty, Kenneth Rice, Nona Sotoodehnia, Alessandro De Grandi, Christian Fuchsberger, Cristian Pattaro, Peter P. Pramstaller, Ian Ford, J. Wouter Jukema, Peter W. Macfarlane, Stella Trompet, Marcus Dörr, Stephan B. Felix, Uwe Völker, Stefan Weiss, Aki S. Havulinna, Antti Jula, Katri Sääksjärvi, Veikko Salomaa, Xiuqing Guo, Susan R. Heckbert, Henry J. Lin, Jerome I. Rotter, Kent D. Taylor, Jie Yao, Renée de Mutsert, Arie C. Maan, Dennis O. Mook-Kanamori, Raymond Noordam, Francesco Cucca, Jun Ding, Edward G. Lakatta, Yong Qian, Kirill V. Tarasov, Daniel Levy, Honghuang Lin, Christopher H. Newton-Cheh, Kathryn L. Lunetta, Alison D. Murray, David J. Porteous, Blair H. Smith, Bruno H. Stricker, André Uitterlinden, Marten E. van den Berg, Jeffrey Haessler, Rebecca D. Jackson, Charles Kooperberg, Ulrike Peters, Alexander P. Reiner, Eric A. Whitsel, Alvaro Alonso, Dan E. Arking, Eric Boerwinkle, Georg B. Ehret, Elsayed Z. Soliman, Christy L. Avery, Stephanie M. Gogarten, Kathleen F. Kerr, Cathy C. Laurie, Amanda A. Seyerle, Adrienne Stilp, Solmaz Assa, M. Abdullah Said, M. Yldau van der Ende, Pier D. Lambiase, Michele Orini, Julia Ramirez, Stefan Van Duijvenboden, David O. Arnar, Daniel F. Gudbjartsson, Hilma Holm, Patrick Sulem, Gudmar Thorleifsson, Rosa B. Thorolfsdottir, Unnur Thorsteinsdottir, Emelia J. Benjamin, Andrew Tinker, Kari Stefansson, Patrick T. Ellinor, Yalda Jamshidi, Steven A. Lubitz, and Patricia B. Munroe

Subjects
Science
Abstract

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Published
2020
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18. Detecting Coronary Artery Disease Using Rest Seismocardiography and Gyrocardiography

Author

Parastoo Dehkordi, Erwin P. Bauer, Kouhyar Tavakolian, Zhen G. Xiao, Andrew P. Blaber, and Farzad Khosrow-Khavar

Subjects
seismocardiography, gyrocardiography, coronary artery disease (CAD), cardiac mechanical activity, angiography, Physiology, QP1-981
Abstract

In this study, we present a non-invasive solution to identify patients with coronary artery disease (CAD) defined as ⩾50% stenosis in at least one coronary artery. The solution is based on the analysis of linear acceleration (seismocardiogram, SCG) and angular velocity (gyrocardiogram, GCG) of the heart recorded in the x, y, and z directional axes from an accelerometer/gyroscope sensor mounted on the sternum. The database was collected from 310 individuals through a multicenter study. The time-frequency features extracted from each SCG and GCG data channel were fed to a one-dimensional Convolutional Neural Network (1D CNN) to train six separate classifiers. The results from different classifiers were later fused to estimate the CAD risk for each participant. The predicted CAD risk was validated against related results from angiography. The SCG z and SCG y classifiers showed better performance relative to the other models (p < 0.05) with the area under the curve (AUC) of 91%. The sensitivity range for CAD detection was 92–94% for the SCG models and 73–87% for the GCG models. Based on our findings, the SCG models achieved better performance in predicting the CAD risk compared to the GCG models; the model based on the combination of all SCG and GCG classifiers did not achieve higher performance relative to the other models. Moreover, these findings showed that the performance of the proposed 3-axial SCG/GCG solution based on recordings obtained during rest was comparable, or better than stress ECG. These data may indicate that 3-axial SCG/GCG could be used as a portable at-home CAD screening tool.

Published
2021
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19. Interaction-Based Feature Selection Algorithm Outperforms Polygenic Risk Score in Predicting Parkinson’s Disease Status

Author

Justin L. Cope, Hannes A. Baukmann, Jörn E. Klinger, Charles N. J. Ravarani, Erwin P. Böttinger, Stefan Konigorski, and Marco F. Schmidt

Subjects
epistasis, machine learning, feature selection, parkinson's disease, PPMI (parkinson’s progression markers initiative), Genetics, QH426-470
Abstract

Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson’s Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson’s disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem.

Published
2021
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20. Factors Associated With Longitudinal Psychological and Physiological Stress in Health Care Workers During the COVID-19 Pandemic: Observational Study Using Apple Watch Data

Author

Robert P Hirten, Matteo Danieletto, Lewis Tomalin, Katie Hyewon Choi, Micol Zweig, Eddye Golden, Sparshdeep Kaur, Drew Helmus, Anthony Biello, Renata Pyzik, Claudia Calcagno, Robert Freeman, Bruce E Sands, Dennis Charney, Erwin P Bottinger, James W Murrough, Laurie Keefer, Mayte Suarez-Farinas, Girish N Nadkarni, and Zahi A Fayad

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundThe COVID-19 pandemic has resulted in a high degree of psychological distress among health care workers (HCWs). There is a need to characterize which HCWs are at an increased risk of developing psychological effects from the pandemic. Given the differences in the response of individuals to stress, an analysis of both the perceived and physiological consequences of stressors can provide a comprehensive evaluation of its impact. ObjectiveThis study aimed to determine characteristics associated with longitudinal perceived stress in HCWs and to assess whether changes in heart rate variability (HRV), a marker of autonomic nervous system function, are associated with features protective against longitudinal stress. MethodsHCWs across 7 hospitals in New York City, NY, were prospectively followed in an ongoing observational digital study using the custom Warrior Watch Study app. Participants wore an Apple Watch for the duration of the study to measure HRV throughout the follow-up period. Surveys measuring perceived stress, resilience, emotional support, quality of life, and optimism were collected at baseline and longitudinally. ResultsA total of 361 participants (mean age 36.8, SD 10.1 years; female: n=246, 69.3%) were enrolled. Multivariate analysis found New York City’s COVID-19 case count to be associated with increased longitudinal stress (P=.008). Baseline emotional support, quality of life, and resilience were associated with decreased longitudinal stress (P

Published
2021
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21. Associations of autozygosity with a broad range of human phenotypes

Author

David W Clark, Yukinori Okada, Kristjan H S Moore, Dan Mason, Nicola Pirastu, Ilaria Gandin, Hannele Mattsson, Catriona L K Barnes, Kuang Lin, Jing Hua Zhao, Patrick Deelen, Rebecca Rohde, Claudia Schurmann, Xiuqing Guo, Franco Giulianini, Weihua Zhang, Carolina Medina-Gomez, Robert Karlsson, Yanchun Bao, Traci M Bartz, Clemens Baumbach, Ginevra Biino, Matthew J Bixley, Marco Brumat, Jin-Fang Chai, Tanguy Corre, Diana L Cousminer, Annelot M Dekker, David A Eccles, Kristel R van Eijk, Christian Fuchsberger, He Gao, Marine Germain, Scott D Gordon, Hugoline G de Haan, Sarah E Harris, Edith Hofer, Alicia Huerta-Chagoya, Catherine Igartua, Iris E Jansen, Yucheng Jia, Tim Kacprowski, Torgny Karlsson, Marcus E Kleber, Shengchao Alfred Li, Ruifang Li-Gao, Anubha Mahajan, Koichi Matsuda, Karina Meidtner, Weihua Meng, May E Montasser, Peter J van der Most, Matthias Munz, Teresa Nutile, Teemu Palviainen, Gauri Prasad, Rashmi B Prasad, Tallapragada Divya Sri Priyanka, Federica Rizzi, Erika Salvi, Bishwa R Sapkota, Daniel Shriner, Line Skotte, Melissa C Smart, Albert Vernon Smith, Ashley van der Spek, Cassandra N Spracklen, Rona J Strawbridge, Salman M Tajuddin, Stella Trompet, Constance Turman, Niek Verweij, Clara Viberti, Lihua Wang, Helen R Warren, Robyn E Wootton, Lisa R Yanek, Jie Yao, Noha A Yousri, Wei Zhao, Adebowale A Adeyemo, Saima Afaq, Carlos Alberto Aguilar-Salinas, Masato Akiyama, Matthew L Albert, Matthew A Allison, Maris Alver, Tin Aung, Fereidoun Azizi, Amy R Bentley, Heiner Boeing, Eric Boerwinkle, Judith B Borja, Gert J de Borst, Erwin P Bottinger, Linda Broer, Harry Campbell, Stephen Chanock, Miao-Li Chee, Guanjie Chen, Yii-Der I Chen, Zhengming Chen, Yen-Feng Chiu, Massimiliano Cocca, Francis S Collins, Maria Pina Concas, Janie Corley, Giovanni Cugliari, Rob M van Dam, Anna Damulina, Maryam S Daneshpour, Felix R Day, Graciela E Delgado, Klodian Dhana, Alexander S F Doney, Marcus Dörr, Ayo P Doumatey, Nduna Dzimiri, S Sunna Ebenesersdóttir, Joshua Elliott, Paul Elliott, Ralf Ewert, Janine F Felix, Krista Fischer, Barry I Freedman, Giorgia Girotto, Anuj Goel, Martin Gögele, Mark O Goodarzi, Mariaelisa Graff, Einat Granot-Hershkovitz, Francine Grodstein, Simonetta Guarrera, Daniel F Gudbjartsson, Kamran Guity, Bjarni Gunnarsson, Yu Guo, Saskia P Hagenaars, Christopher A Haiman, Avner Halevy, Tamara B Harris, Mehdi Hedayati, David A van Heel, Makoto Hirata, Imo Höfer, Chao Agnes Hsiung, Jinyan Huang, Yi-Jen Hung, M Arfan Ikram, Anuradha Jagadeesan, Pekka Jousilahti, Yoichiro Kamatani, Masahiro Kanai, Nicola D Kerrison, Thorsten Kessler, Kay-Tee Khaw, Chiea Chuen Khor, Dominique P V de Kleijn, Woon-Puay Koh, Ivana Kolcic, Peter Kraft, Bernhard K Krämer, Zoltán Kutalik, Johanna Kuusisto, Claudia Langenberg, Lenore J Launer, Deborah A Lawlor, I-Te Lee, Wen-Jane Lee, Markus M Lerch, Liming Li, Jianjun Liu, Marie Loh, Stephanie J London, Stephanie Loomis, Yingchang Lu, Jian’an Luan, Reedik Mägi, Ani W Manichaikul, Paolo Manunta, Gísli Másson, Nana Matoba, Xue W Mei, Christa Meisinger, Thomas Meitinger, Massimo Mezzavilla, Lili Milani, Iona Y Millwood, Yukihide Momozawa, Amy Moore, Pierre-Emmanuel Morange, Hortensia Moreno-Macías, Trevor A Mori, Alanna C Morrison, Taulant Muka, Yoshinori Murakami, Alison D Murray, Renée de Mutsert, Josyf C Mychaleckyj, Mike A Nalls, Matthias Nauck, Matt J Neville, Ilja M Nolte, Ken K Ong, Lorena Orozco, Sandosh Padmanabhan, Gunnar Pálsson, James S Pankow, Cristian Pattaro, Alison Pattie, Ozren Polasek, Neil Poulter, Peter P Pramstaller, Lluis Quintana-Murci, Katri Räikkönen, Sarju Ralhan, Dabeeru C Rao, Wouter van Rheenen, Stephen S Rich, Paul M Ridker, Cornelius A Rietveld, Antonietta Robino, Frank J A van Rooij, Daniela Ruggiero, Yasaman Saba, Charumathi Sabanayagam, Maria Sabater-Lleal, Cinzia Felicita Sala, Veikko Salomaa, Kevin Sandow, Helena Schmidt, Laura J Scott, William R Scott, Bahareh Sedaghati-Khayat, Bengt Sennblad, Jessica van Setten, Peter J Sever, Wayne H-H Sheu, Yuan Shi, Smeeta Shrestha, Sharvari Rahul Shukla, Jon K Sigurdsson, Timo Tonis Sikka, Jai Rup Singh, Blair H Smith, Alena Stančáková, Alice Stanton, John M Starr, Lilja Stefansdottir, Leon Straker, Patrick Sulem, Gardar Sveinbjornsson, Morris A Swertz, Adele M Taylor, Kent D Taylor, Natalie Terzikhan, Yih-Chung Tham, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Annika Tillander, Russell P Tracy, Teresa Tusié-Luna, Ioanna Tzoulaki, Simona Vaccargiu, Jagadish Vangipurapu, Jan H Veldink, Veronique Vitart, Uwe Völker, Eero Vuoksimaa, Salma M Wakil, Melanie Waldenberger, Gurpreet S Wander, Ya Xing Wang, Nicholas J Wareham, Sarah Wild, Chittaranjan S Yajnik, Jian-Min Yuan, Lingyao Zeng, Liang Zhang, Jie Zhou, Najaf Amin, Folkert W Asselbergs, Stephan J L Bakker, Diane M Becker, Benjamin Lehne, David A Bennett, Leonard H van den Berg, Sonja I Berndt, Dwaipayan Bharadwaj, Lawrence F Bielak, Murielle Bochud, Mike Boehnke, Claude Bouchard, Jonathan P Bradfield, Jennifer A Brody, Archie Campbell, Shai Carmi, Mark J Caulfield, David Cesarini, John C Chambers, Giriraj Ratan Chandak, Ching-Yu Cheng, Marina Ciullo, Marilyn Cornelis, Daniele Cusi, George Davey Smith, Ian J Deary, Rajkumar Dorajoo, Cornelia M van Duijn, David Ellinghaus, Jeanette Erdmann, Johan G Eriksson, Evangelos Evangelou, Michele K Evans, Jessica D Faul, Bjarke Feenstra, Mary Feitosa, Sylvain Foisy, Andre Franke, Yechiel Friedlander, Paolo Gasparini, Christian Gieger, Clicerio Gonzalez, Philippe Goyette, Struan F A Grant, Lyn R Griffiths, Leif Groop, Vilmundur Gudnason, Ulf Gyllensten, Hakon Hakonarson, Anders Hamsten, Pim van der Harst, Chew-Kiat Heng, Andrew A Hicks, Hagit Hochner, Heikki Huikuri, Steven C Hunt, Vincent W V Jaddoe, Philip L De Jager, Magnus Johannesson, Åsa Johansson, Jost B Jonas, J Wouter Jukema, Juhani Junttila, Jaakko Kaprio, Sharon L. R. Kardia, Fredrik Karpe, Meena Kumari, Markku Laakso, Sander W van der Laan, Jari Lahti, Matthias Laudes, Rodney A Lea, Wolfgang Lieb, Thomas Lumley, Nicholas G Martin, Winfried März, Giuseppe Matullo, Mark I McCarthy, Sarah E Medland, Tony R Merriman, Andres Metspalu, Brian F Meyer, Karen L Mohlke, Grant W Montgomery, Dennis Mook-Kanamori, Patricia B Munroe, Kari E North, Dale R Nyholt, Jeffery R O’connell, Carole Ober, Albertine J Oldehinkel, Walter Palmas, Colin Palmer, Gerard G Pasterkamp, Etienne Patin, Craig E Pennell, Louis Perusse, Patricia A Peyser, Mario Pirastu, Tinca J. C. Polderman, David J Porteous, Danielle Posthuma, Bruce M Psaty, John D Rioux, Fernando Rivadeneira, Charles Rotimi, Jerome I Rotter, Igor Rudan, Hester M Den Ruijter, Dharambir K Sanghera, Naveed Sattar, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Robert A Scott, Alan R Shuldiner, Xueling Sim, Neil Small, Jennifer A Smith, Nona Sotoodehnia, E-Shyong Tai, Alexander Teumer, Nicholas J Timpson, Daniela Toniolo, David-Alexandre Tregouet, Tiinamaija Tuomi, Peter Vollenweider, Carol A Wang, David R Weir, John B Whitfield, Cisca Wijmenga, Tien-Yin Wong, John Wright, Jingyun Yang, Lei Yu, Babette S Zemel, Alan B Zonderman, Markus Perola, Patrik K. E. Magnusson, André G Uitterlinden, Jaspal S Kooner, Daniel I Chasman, Ruth J. F. Loos, Nora Franceschini, Lude Franke, Chris S Haley, Caroline Hayward, Robin G Walters, John R. B. Perry, Tōnu Esko, Agnar Helgason, Kari Stefansson, Peter K Joshi, Michiaki Kubo, and James F Wilson

Subjects
Science
Abstract

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Published
2019
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29. Global decoupling of functional and phylogenetic diversity in plant communities

Author

Hähn, Georg J. A., Damasceno, Gabriella, Alvarez-Davila, Esteban, Aubin, Isabelle, Bauters, Marijn, Bergmeier, Erwin, Biurrun, Idoia, Bjorkman, Anne D., Bonari, Gianmaria, Botta-Dukát, Zoltán, Campos, Juan A., Čarni, Andraž, Chytrý, Milan, Ćušterevska, Renata, de Gasper, André Luís, De Sanctis, Michele, Dengler, Jürgen, Dolezal, Jiri, El-Sheikh, Mohamed A., Finckh, Manfred, Galán-de-Mera, Antonio, Garbolino, Emmanuel, Gholizadeh, Hamid, Golub, Valentin, Haider, Sylvia, Hatim, Mohamed Z., Hérault, Bruno, Homeier, Jürgen, Jandt, Ute, Jansen, Florian, Jentsch, Anke, Kattge, Jens, Kessler, Michael, Khanina, Larisa, Kreft, Holger, Küzmič, Filip, Lenoir, Jonathan, Moeslund, Jesper Erenskjold, Mucina, Ladislav, Naqinezhad, Alireza, Noroozi, Jalil, Pérez-Haase, Aaron, Phillips, Oliver L., Pillar, Valério D., Rivas-Torres, Gonzalo, Ruprecht, Eszter, Sandel, Brody, Schmidt, Marco, Schmiedel, Ute, Schnitzer, Stefan, Schrodt, Franziska, Šilc, Urban, Sparrow, Ben, Sporbert, Maria, Stančić, Zvjezdana, Strohbach, Ben, Svenning, Jens-Christian, Tang, Cindy Q., Tang, Zhiyao, Vibrans, Alexander Christian, Violle, Cyrille, Waller, Donald, Wana, Desalegn, Wang, Hua-Feng, Whitfeld, Timothy, Zizka, Georg, Sabatini, Francesco Maria, and Bruelheide, Helge

Published
2024
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31. Preventive Measures and Risk Factors for Post-ERCP Pancreatitis: A Systematic Review and Individual Patient Data Meta-Analysis

Author

Sperna Weiland, Christina J., Akshintala, Venkata S., Singh, Anmol, Buxbaum, James, Choi, Jun-Ho, Elmunzer, Badih J., Fogel, Evan S., Lai, Jian-Han, Levenick, John M., Gardner, Timothy B., Lua, Guan W., Luo, Hui, de Jong, Mike, Mok, Shaffer R. S., Phillip, Veit, Singh, Vikesh, Siersema, Peter D., Drenth, Joost P. H., and van Geenen, Erwin J. M.

Published
2024
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44. Association of SARS-CoV-2 viral load at admission with in-hospital acute kidney injury: A retrospective cohort study.

Author

Ishan Paranjpe, Kumardeep Chaudhary, Kipp W Johnson, Suraj K Jaladanki, Shan Zhao, Jessica K De Freitas, Elisabet Pujdas, Fayzan Chaudhry, Erwin P Bottinger, Matthew A Levin, Zahi A Fayad, Alexander W Charney, Jane Houldsworth, Carlos Cordon-Cardo, Benjamin S Glicksberg, and Girish N Nadkarni

Subjects
Medicine, Science
Abstract

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated Coronavirus Disease 2019 (COVID-19) is a public health emergency. Acute kidney injury (AKI) is a common complication in hospitalized patients with COVID-19 although mechanisms underlying AKI are yet unclear. There may be a direct effect of SARS-CoV-2 virus on the kidney; however, there is currently no data linking SARS-CoV-2 viral load (VL) to AKI. We explored the association of SARS-CoV-2 VL at admission to AKI in a large diverse cohort of hospitalized patients with COVID-19.Methods and findingsWe included patients hospitalized between March 13th and May 19th, 2020 with SARS-CoV-2 in a large academic healthcare system in New York City (N = 1,049) with available VL at admission quantified by real-time RT-PCR. We extracted clinical and outcome data from our institutional electronic health records (EHRs). AKI was defined by KDIGO guidelines. We fit a Fine-Gray competing risks model (with death as a competing risk) using demographics, comorbidities, admission severity scores, and log10 transformed VL as covariates and generated adjusted hazard ratios (aHR) and 95% Confidence Intervals (CIs). VL was associated with an increased risk of AKI (aHR = 1.04, 95% CI: 1.01-1.08, p = 0.02) with a 4% increased hazard for each log10 VL change. Patients with a viral load in the top 50th percentile had an increased adjusted hazard of 1.27 (95% CI: 1.02-1.58, p = 0.03) for AKI as compared to those in the bottom 50th percentile.ConclusionsVL is weakly but significantly associated with in-hospital AKI after adjusting for confounders. This may indicate the role of VL in COVID-19 associated AKI. This data may inform future studies to discover the mechanistic basis of COVID-19 associated AKI.

Published
2021
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45. Retrospective cohort study of clinical characteristics of 2199 hospitalised patients with COVID-19 in New York City

Author

Girish N Nadkarni, Zahi A Fayad, Benjamin S Glicksberg, David L Reich, Prem Timsina, Arash Kia, Patricia Kovatch, Jessica K De Freitas, Paul O’Reilly, Allan Just, Dennis Charney, Ishan Paranjpe, Ross O'Hagan, Adam J Russak, Anuradha Lala, Riccardo Miotto, Akhil Vaid, Kipp W Johnson, Matteo Danieletto, Eddye Golden, Dara Meyer, Manbir Singh, Sulaiman Somani, Arjun Kapoor, Sayan Manna, Udit Nangia, Suraj K Jaladanki, Laura M Huckins, Patricia Glowe, Robert M Freeman, Matthew A Levin, Jeffrey Jhang, Adolfo Firpo, Joseph Finkelstein, Judith A Aberg, Emilia Bagiella, Carol R Horowitz, Barbara Murphy, Jagat Narula, Eric J Nestler, V Fuster, Carlos Cordon-Cardo, Erwin P Bottinger, and Alexander W Charney

Subjects
Medicine
Abstract

Objective The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive.Design Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive.Setting All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system.Participants Participants over the age of 18 years were included.Primary outcomes We investigated in-hospital mortality during the study period.Results A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 μg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 μg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL.Conclusions In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.

Published
2020
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46. Visualizing the Contribution of Keratin-14+ Limbal Epithelial Precursors in Corneal Wound Healing

Author

Mijeong Park, Alexander Richardson, Elvis Pandzic, Erwin P. Lobo, Renee Whan, Stephanie L. Watson, J. Guy Lyons, Denis Wakefield, and Nick Di Girolamo

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Summary: It is thought that corneal epithelial injuries resolve by leading-edge cells “sliding” or “rolling” into the wound bed. Here, we challenge this notion and show by real-time imaging that corneal wounds initially heal by “basal cell migration.” The K14CreERT2-Confetti multi-colored reporter mouse was employed to spatially and temporally fate-map cellular behavior during corneal wound healing. Keratin-14+ basal epithelia are forced into the wound bed by increased population pressure gradient from the limbus to the wound edge. As the defect resolves, centripetally migrating epithelia decelerate and replication in the periphery is reduced. With time, keratin-14+-derived clones diminish in number concomitant with their expansion, indicative that clonal evolution aligns with neutral drifting. These findings have important implications for the involvement of stem cells in acute tissue regeneration, in key sensory tissues such as the cornea. : In this article, Di Girolamo and colleagues visualized the contribution of K14+ limbal epithelial precursors in resolving corneal epithelial debridement wounds. They noted that population pressure from the limbal perimeter is the main driver of K14+ basal cell displacement during the initial phase of injury repair. Keywords: cornea wound healing, limbal epithelial stem cells, K14CreERT2-Confetti transgenic mice, basal cell migration, organ-culture system, spatiotemporal image correlation spectroscopy, computational modeling

Published
2019
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47. Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies

Author

Andrew P. Morris, Thu H. Le, Haojia Wu, Artur Akbarov, Peter J. van der Most, Gibran Hemani, George Davey Smith, Anubha Mahajan, Kyle J. Gaulton, Girish N. Nadkarni, Adan Valladares-Salgado, Niels Wacher-Rodarte, Josyf C. Mychaleckyj, Nicole D. Dueker, Xiuqing Guo, Yang Hai, Jeffrey Haessler, Yoichiro Kamatani, Adrienne M. Stilp, Gu Zhu, James P. Cook, Johan Ärnlöv, Susan H. Blanton, Martin H. de Borst, Erwin P. Bottinger, Thomas A. Buchanan, Sylvia Cechova, Fadi J. Charchar, Pei-Lun Chu, Jeffrey Damman, James Eales, Ali G. Gharavi, Vilmantas Giedraitis, Andrew C. Heath, Eli Ipp, Krzysztof Kiryluk, Holly J. Kramer, Michiaki Kubo, Anders Larsson, Cecilia M. Lindgren, Yingchang Lu, Pamela A. F. Madden, Grant W. Montgomery, George J. Papanicolaou, Leslie J. Raffel, Ralph L. Sacco, Elena Sanchez, Holger Stark, Johan Sundstrom, Kent D. Taylor, Anny H. Xiang, Aleksandra Zivkovic, Lars Lind, Erik Ingelsson, Nicholas G. Martin, John B. Whitfield, Jianwen Cai, Cathy C. Laurie, Yukinori Okada, Koichi Matsuda, Charles Kooperberg, Yii-Der Ida Chen, Tatjana Rundek, Stephen S. Rich, Ruth J. F. Loos, Esteban J. Parra, Miguel Cruz, Jerome I. Rotter, Harold Snieder, Maciej Tomaszewski, Benjamin D. Humphreys, and Nora Franceschini

Subjects
Science
Abstract

Estimated glomerular filtration rate (eGFR) is a measure of kidney function used to define chronic kidney disease. Here, Morris et al. perform trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals and identify novel loci and downstream putative causal genes.

Published
2019
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48. Policy Levers to Advance Credential Transparency. Policy Brief

Author

Education Commission of the States (ECS), Lexi Anderson, Ben Erwin, and Zeke Perez

Abstract

There are nearly 1 million credentials in the United States that students and workers can take advantage of, but how information about these credentials is collected and communicated is oftentimes inconsistent and hard to access. In February, we invited a group of postsecondary and workforce development experts to consider how policymakers can leverage credential transparency to further state workforce and attainment goals. Inspired by those conversations, this Policy Brief highlights data capacity, governance and funding as key policy areas and provides considerations that states, systems and practitioners can use to develop credential transparency. [This brief was produced with Credential Engine.]

Published
2023

49. Keratin-14-Positive Precursor Cells Spawn a Population of Migratory Corneal Epithelia that Maintain Tissue Mass throughout Life

Author

Alexander Richardson, Erwin P. Lobo, Naomi C. Delic, Mary R. Myerscough, J. Guy Lyons, Denis Wakefield, and Nick Di Girolamo

Subjects
cornea, epithelium, stem cell, development, lineage tracing, limbus, Confetti mouse, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

The dynamics of epithelial stem cells (SCs) that contribute to the formation and maintenance of the cornea are poorly understood. Here, we used K14CreERT2-Confetti (Confetti) mice, sophisticated imaging, and computational modeling to trace the origins and fate of these cells during embryogenesis and adult life. We show that keratin-14 (K14+)-expressing progenitors are defined and widely distributed across the E16.5 cornea, after which they undergo cycles of proliferation and dispersal prior to eyelid opening. K14+ clonal patches disappear from the central cornea and are replaced by limbal-derived K14+ streaks, a finding that aligned with bromodeoxyuridine label-retaining studies. We also elucidated the mechanism by which SC clones are lost during life and propose this is due to population asymmetry and neutral drift. Finally, we established that the occurrence of an equatorial migratory mid-line is a consequence of apoptosis in a narrow nasal-temporal region, the site where eyelids meet during blinking.

Published
2017
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50. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author

Aurélien Macé, Marcus A. Tuke, Patrick Deelen, Kati Kristiansson, Hannele Mattsson, Margit Nõukas, Yadav Sapkota, Ursula Schick, Eleonora Porcu, Sina Rüeger, Aaron F. McDaid, David Porteous, Thomas W. Winkler, Erika Salvi, Nick Shrine, Xueping Liu, Wei Q. Ang, Weihua Zhang, Mary F. Feitosa, Cristina Venturini, Peter J. van der Most, Anders Rosengren, Andrew R. Wood, Robin N. Beaumont, Samuel E. Jones, Katherine S. Ruth, Hanieh Yaghootkar, Jessica Tyrrell, Aki S. Havulinna, Harmen Boers, Reedik Mägi, Jennifer Kriebel, Martina Müller-Nurasyid, Markus Perola, Markku Nieminen, Marja-Liisa Lokki, Mika Kähönen, Jorma S. Viikari, Frank Geller, Jari Lahti, Aarno Palotie, Päivikki Koponen, Annamari Lundqvist, Harri Rissanen, Erwin P. Bottinger, Saima Afaq, Mary K. Wojczynski, Petra Lenzini, Ilja M. Nolte, Thomas Sparsø, Nicole Schupf, Kaare Christensen, Thomas T. Perls, Anne B. Newman, Thomas Werge, Harold Snieder, Timothy D. Spector, John C. Chambers, Seppo Koskinen, Mads Melbye, Olli T. Raitakari, Terho Lehtimäki, Martin D. Tobin, Louise V. Wain, Juha Sinisalo, Annette Peters, Thomas Meitinger, Nicholas G. Martin, Naomi R. Wray, Grant W. Montgomery, Sarah E. Medland, Morris A. Swertz, Erkki Vartiainen, Katja Borodulin, Satu Männistö, Anna Murray, Murielle Bochud, Sébastien Jacquemont, Fernando Rivadeneira, Thomas F. Hansen, Albertine J. Oldehinkel, Massimo Mangino, Michael A. Province, Panos Deloukas, Jaspal S. Kooner, Rachel M. Freathy, Craig Pennell, Bjarke Feenstra, David P. Strachan, Guillaume Lettre, Joel Hirschhorn, Daniele Cusi, Iris M. Heid, Caroline Hayward, Katrin Männik, Jacques S. Beckmann, Ruth J. F. Loos, Dale R. Nyholt, Andres Metspalu, Johan G. Eriksson, Michael N. Weedon, Veikko Salomaa, Lude Franke, Alexandre Reymond, Timothy M. Frayling, and Zoltán Kutalik

Subjects
Science
Abstract

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Published
2017
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