bluuebunny/crossref_metadata_2025_split huggingface dataset:
OrgDyn: feature- and model-based characterization of spatial and temporal organoid dynamics
Authors: Hasnain Zaki , Fraser Andrew K , Georgess Dan , Choi Alex , Macklin Paul , Bader Joel S , Peyton Shelly R , Ewald Andrew J , Newton Paul K 
Published: February 2020

AbstractSummaryOrganoid model systems recapitulate key features of mammalian tissues and enable high throughput experiments. However, the impact of these experiments may be limited by manual, non-standardized, static or qualitative phenotypic analysis. OrgDyn is an open-source and modular pipeline to quantify organoid shape dynamics using a combination of feature- and model-based approaches on time series of 2D organoid contour images. Our pipeline consists of (i) geometrical and signal processing feature extraction, (ii) dimensionality reduction to differentiate dynamical paths, (iii) time series clustering to identify coherent groups of organoids and (iv) dynamical modeling using point distribution models to explain temporal shape variation. OrgDyn can characterize, cluster and model differences among unique dynamical paths that define diverse final shapes, thus enabling quantitative analysis of the molecular basis of tissue development and disease.Availability and Implementationhttps://github.com/zakih/organoidDynamics (BSD 3-Clause License).Supplementary informationSupplementary data are available at Bioinformatics online.
Multiway generalized canonical correlation analysis
Authors: Gloaguen Arnaud , Philippe Cathy , Frouin Vincent , Gennari Giulia , Dehaene-Lambertz Ghislaine , Le Brusquet Laurent , Tenenhaus Arthur 
Published: February 2020

SummaryRegularized generalized canonical correlation analysis (RGCCA) is a general multiblock data analysis framework that encompasses several important multivariate analysis methods such as principal component analysis, partial least squares regression, and several versions of generalized canonical correlation analysis. In this article, we extend RGCCA to the case where at least one block has a tensor structure. This method is called multiway generalized canonical correlation analysis (MGCCA). Convergence properties of the MGCCA algorithm are studied, and computation of higher-level components are discussed. The usefulness of MGCCA is shown on simulation and on the analysis of a cognitive study in human infants using electroencephalography (EEG).
Unique shoot architecture in the leafy liverwortHerzogianthus vaginatus(Herzogianthaceae): insights into novel growth patterns in Jungermanniidae
Authors: Renner Matt A M , Salter Joshua 
Published: February 2020

AbstractAll studied leafy liverworts have shoots with leaf to underleaf ratios of either 2:1 or 1:1. These ratios are the product of growth by either helical or pendular segmentation of the tetrahedral apical cell. Here we report that Herzogianthus vaginatus has a leaf to underleaf ratio approaching 3:1 on primary shoots, and on secondary shoots the ratio is closer to 4:1. These ratios are incompatible with the simple helical or pendular growth patterns found in other leafy liverworts. Further, the sequence of leaves and underleaves on Herzogianthus shoots is not wholly regular, which is previously unrecorded. We assess potential growth models that may explain the leaf to underleaf ratios and architecture of Herzogianthus shoots, including (1) branch modification, (2) merophyte or leaf-initial duplication and (3) changes in segmentation sequences. We compared leaf sequences produced by pendular and helical segmentation and a range of non-standard models, with sequences observed on shoots of Herzogianthus. Structure allows us to discriminate between the many alternative growth models, because each make testable predictions about leaf and underleaf sequences. We propose that Herzogianthus possesses growth processes unique among leafy liverworts, in which the direction of helication periodically and, sometimes irregularly, reverses. This, in combination with the secondary shoots having different growth patterns from primary shoots, emphasizes that Herzogianthus warrants detailed histological study to test our proposition.
Phylogenetics of the mycoheterotrophic genusThismia(Thismiaceae: Dioscoreales) with a focus on the Old World taxa: delineation of novel natural groups and insights into the evolution of morphological traits
Authors: Shepeleva Ekaterina A , Schelkunov Mikhail I , Hroneš Michal , Sochor Michal , Dančák Martin , Merckx Vincent Sft , Kikuchi Izai Abs , Chantanaorrapint Sahut , Suetsugu Kenji , Tsukaya Hirokazu , Mar Shek S , Luu Hong Truong , Li Hong-Qing , Logacheva Maria D , Nuraliev Maxim S 
Published: February 2020

AbstractThismia is a genus of &gt; 80 mycoheterotrophic species characterized by a peculiar appearance and complex floral morphology. A significant proportion of the species and morphological diversity of Thismia has only been uncovered in the past two decades, and new discoveries continue to be made. Given that many new data have recently become available, and the most comprehensive taxonomic revision of the genus from 1938 addresses less than half of the currently known species, previous hypotheses for species relationships and infrageneric taxonomic classification in Thismia was in need of review. Extensive molecular phylogenetic studies of Thismia at the genus level have never been presented. We investigate the phylogenetic relationships of 41 species (and one variety) of Thismia from the Old World. Our study comprises 68 specimens (for 28 of which the data were newly generated), including outgroup taxa broadly representing Thismiaceae (= Burmanniaceae p.p. sensuAPG IV, 2016), and is based on two nuclear and one mitochondrial marker. We use maximum likelihood and Bayesian inference to infer relationships among the taxa. We also constructed a morphological dataset of 12 mostly floral characters, comparing these characters to hypotheses based on molecular evidence to identify putative synapomorphies for major clades and to discuss hypotheses regarding the evolution of structural traits in the genus. Our analyses indicate that the majority of currently accepted infrageneric taxa of Thismia are polyphyletic. We find support for the monophyly of the Old World group, in which we recognize five well-supported lineages (clades); the only New World species studied appears to be related to the Neotropical genus Tiputinia. Ancestral state reconstructions demonstrate that the evolution of most morphological characters was homoplastic, but we identify characters that provide each of the five clades of Old World Thismia with a unique morphological description. The geographical distribution of the species under study is also shown to be consistent with the major clades. Our investigation provides a phylogenetic basis for the development of a novel sectional classification of Thismia reflecting morphological and geographical traits.
Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function
Authors: Zilmer Monica , Edmondson Andrew C , Khetarpal Sumeet A , Alesi Viola , Zaki Maha S , Rostasy Kevin , Madsen Camilla G , Lepri Francesca R , Sinibaldi Lorenzo , Cusmai Raffaella , Novelli Antonio , Issa Mahmoud Y , Fenger Christina D , Abou Jamra Rami , Reutter Heiko , Briuglia Silvana , Agolini Emanuele , Hansen Lars , Petäjä-Repo Ulla E , Hintze John , Raymond Kimiyo M , Liedtke Kristen , Stanley Valentina , Musaev Damir , Gleeson Joseph G , Vitali Cecilia , O’Brien W Timothy , Gardella Elena , Rubboli Guido , Rader Daniel J , Schjoldager Katrine T , Møller Rikke S 
Published: February 2020

Abstract
Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 encodes the Golgi-localized polypeptide N-acetyl-d-galactosamine-transferase 2 isoenzyme. GALNT2 is widely expressed in most cell types and directs initiation of mucin-type protein O-glycosylation. All patients showed loss of O-glycosylation of apolipoprotein C-III, a non-redundant substrate for GALNT2. Patients with GALNT2-CDG generally exhibit a syndrome characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. In behavioural studies, GALNT2-CDG mice demonstrated cerebellar motor deficits, decreased sociability, and impaired sensory integration and processing. The multisystem nature of phenotypes in patients and rodent models of GALNT2-CDG suggest that there are multiple non-redundant protein substrates of GALNT2 in various tissues, including brain, which are critical to normal growth and development.
Identification of an amino-terminus determinant critical for ryanodine receptor/Ca2+ release channel function
Authors: Seidel Monika , de Meritens Camille Rabesahala , Johnson Louisa , Parthimos Dimitris , Bannister Mark , Thomas Nia Lowri , Ozekhome-Mike Esizaze , Lai Francis Anthony , Zissimopoulos Spyros 
Published: February 2020

Abstract

Aims
The cardiac ryanodine receptor (RyR2), which mediates intracellular Ca2+ release to trigger cardiomyocyte contraction, participates in development of acquired and inherited arrhythmogenic cardiac disease. This study was undertaken to characterize the network of inter- and intra-subunit interactions regulating the activity of the RyR2 homotetramer.

Methods and results
We use mutational investigations combined with biochemical assays to identify the peptide sequence bridging the β8 with β9 strand as the primary determinant mediating RyR2 N-terminus self-association. The negatively charged side chains of two aspartate residues (D179 and D180) within the β8–β9 loop are crucial for the N-terminal inter-subunit interaction. We also show that the RyR2 N-terminus domain interacts with the C-terminal channel pore region in a Ca2+-independent manner. The β8–β9 loop is required for efficient RyR2 subunit oligomerization but it is dispensable for N-terminus interaction with C-terminus. Deletion of the β8–β9 sequence produces unstable tetrameric channels with subdued intracellular Ca2+ mobilization implicating a role for this domain in channel opening. The arrhythmia-linked R176Q mutation within the β8–β9 loop decreases N-terminus tetramerization but does not affect RyR2 subunit tetramerization or the N-terminus interaction with C-terminus. RyR2R176Q is a characteristic hypersensitive channel displaying enhanced intracellular Ca2+ mobilization suggesting an additional role for the β8–β9 domain in channel closing.

Conclusion
These results suggest that efficient N-terminus inter-subunit communication mediated by the β8–β9 loop may constitute a primary regulatory mechanism for both RyR2 channel activation and suppression.
Genome-wide association study on coronary artery disease in type 1 diabetes suggests beta-defensin 127 as a risk locus
Authors: Antikainen Anni A V , Sandholm Niina , Trégouët David-Alexandre , Charmet Romain , McKnight Amy Jayne , Ahluwalia Tarunveer S , Syreeni Anna , Valo Erkka , Forsblom Carol , Gordin Daniel , Harjutsalo Valma , Hadjadj Samy , Maxwell Alexander P , Rossing Peter , Groop Per-Henrik 
Published: February 2020

Abstract

Aims
Diabetes is a known risk factor for coronary artery disease (CAD). There is accumulating evidence that CAD pathogenesis differs for individuals with type 1 diabetes (T1D). However, the genetic background has not been extensively studied. We aimed to discover genetic loci increasing CAD susceptibility, especially in T1D, to examine the function of these discoveries and to study the role of the known risk loci in T1D.

Methods and results
We performed the largest genome-wide association study to date for CAD in T1D, comprising 4869 individuals with T1D (cases/controls: 941/3928). Two loci reached genome-wide significance, rs1970112 in CDKN2B-AS1 [odds ratio (OR) = 1.32, P = 1.50 × 10−8], and rs6055069 on DEFB127 promoter (OR = 4.17, P = 2.35 × 10−9), with consistent results in survival analysis. The CDKN2B-AS1 variant replicated (P = 0.04) when adjusted for diabetic kidney disease in three additional T1D cohorts (cases/controls: 434/3123). Furthermore, we explored the function of the lead discoveries with a cardio-phenome-wide analysis. Among the eight suggestive loci (P &lt; 1 × 10−6), rs70962766 near B3GNT2 associated with central blood pressure, rs1344228 near CNTNAP5 with intima media thickness, and rs2112481 on GRAMD2B promoter with serum leucocyte concentration. Finally, we calculated genetic risk scores for individuals with T1D with the known susceptibility loci. General population risk variants were modestly but significantly associated with CAD also in T1D (P = 4.21 × 10−7).

Conclusion
While general population CAD risk loci had limited effect on the risk in T1D, for the first time, variants at the CDKN2B-AS1 locus were robustly associated with CAD in individuals with T1D. The novel finding on β-defensin DEFB127 promoter provides a link between diabetes, infection susceptibility, and CAD, although pending on future confirmation.
Theoretical signature of a cavern created by an underground nuclear explosion in 2-D exploration seismic data
Authors: Ortiz-Aguilar Stephany , De Basabe Jonas D , Gonzalez-Escobar Mario , Magar Vanesa 
Published: February 2020

SUMMARYThe proliferation of nuclear tests is a problem that threatens the safety and health of everybody. In order to tackle this problem, the UN is promoting the Comprehensive Nuclear-Test-Ban Treaty (CTBT), which includes protocols for monitoring and On-Site Inspections (OSI). The purpose of OSI is to verify if a nuclear test has been carried out by identifying with a geophysical technique the presence of a cavern, hole or some device that indicates the violation of the treaty. In this context, it is desirable to be able to use exploration-seismology techniques to detect caverns created by an underground nuclear explosion. However, there is scarce information about the seismic signature of this type of cavern. We present the results of elastic wave propagation simulations, in the time domain, with a cavern created by an underground nuclear explosion. The wave equation is solved using the spectral element method with 4th order basis functions and quadrilateral elements. We show the results for models with cavities and caverns corresponding to explosions of 1, 20 and 100 kilotons, and obtain seismic traces in which we can observe the effect of the structures. We conclude that caverns created by nuclear explosions can be detected using seismic data and distinguished from caves because they behave like two concentric diffractor bodies, as opposed to caves-like diffractors.
Disturbed genomic imprinting and its relevance for human reproduction: causes and clinical consequences
Authors: Elbracht Miriam , Mackay Deborah , Begemann Matthias , Kagan Karl Oliver , Eggermann Thomas 
Published: February 2020

AbstractBACKGROUNDHuman reproductive issues affecting fetal and maternal health are caused by numerous exogenous and endogenous factors, of which the latter undoubtedly include genetic changes. Pathogenic variants in either maternal or offspring DNA are associated with effects on the offspring including clinical disorders and nonviable outcomes. Conversely, both fetal and maternal factors can affect maternal health during pregnancy. Recently, it has become evident that mammalian reproduction is influenced by genomic imprinting, an epigenetic phenomenon that regulates the expression of genes according to their parent from whom they are inherited. About 1% of human genes are normally expressed from only the maternally or paternally inherited gene copy. Since numerous imprinted genes are involved in (embryonic) growth and development, disturbance of their balanced expression can adversely affect these processes.OBJECTIVE AND RATIONALEThis review summarises current our understanding of genomic imprinting in relation to human ontogenesis and pregnancy and its relevance for reproductive medicine.SEARCH METHODSLiterature databases (Pubmed, Medline) were thoroughly searched for the role of imprinting in human reproductive failure. In particular, the terms ‘multilocus imprinting disturbances, SCMC, NLRP/NALP, imprinting and reproduction’ were used in various combinations.OUTCOMESA range of molecular changes to specific groups of imprinted genes are associated with imprinting disorders, i.e. syndromes with recognisable clinical features including distinctive prenatal features. Whereas the majority of affected individuals exhibit alterations at single imprinted loci, some have multi-locus imprinting disturbances (MLID) with less predictable clinical features. Imprinting disturbances are also seen in some nonviable pregnancy outcomes, such as (recurrent) hydatidiform moles, which can therefore be regarded as a severe form of imprinting disorders. There is growing evidence that MLID can be caused by variants in the maternal genome altering the imprinting status of the oocyte and the embryo, i.e. maternal effect mutations. Pregnancies of women carrying maternal affect mutations can have different courses, ranging from miscarriages to birth of children with clinical features of various imprinting disorders.WIDER IMPLICATIONSIncreasing understanding of imprinting disturbances and their clinical consequences have significant impacts on diagnostics, counselling and management in the context of human reproduction. Defining criteria for identifying pregnancies complicated by imprinting disorders facilitates early diagnosis and personalised management of both the mother and offspring. Identifying the molecular lesions underlying imprinting disturbances (e.g. maternal effect mutations) allows targeted counselling of the family and focused medical care in further pregnancies.
NOX1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset IBD and NOX1 Deficiency
Authors: Khoshnevisan Razieh , Anderson Michael , Babcock Stephen , Anderson Sierra , Illig David , Marquardt Benjamin , Sherkat Roya , Schröder Katrin , Moll Franziska , Hollizeck Sebastian , Rohlfs Meino , Walz Christoph , Adibi Peyman , Rezaei Abbas , Andalib Alireza , Koletzko Sibylle , Muise Aleixo M , Snapper Scott B , Klein Christoph , Thiagarajah Jay R , Kotlarz Daniel 
Published: February 2020

Abstract

Background
Genetic defects of pediatric-onset inflammatory bowel disease (IBD) provide critical insights into molecular factors controlling intestinal homeostasis. NOX1 has been recently recognized as a major source of reactive oxygen species (ROS) in human colonic epithelial cells. Here we assessed the functional consequences of human NOX1 deficiency with respect to wound healing and epithelial migration by studying pediatric IBD patients presenting with a stop-gain mutation in NOX1.

Methods
Functional characterization of the NOX1 variant included ROS generation, wound healing, 2-dimensional collective chemotactic migration, single-cell planktonic migration in heterologous cell lines, and RNA scope and immunohistochemistry of paraffin-embedded patient tissue samples.

Results
Using exome sequencing, we identified a stop-gain mutation in NOX1 (c.160C&gt;T, p.54R&gt;*) in patients with pediatric-onset IBD. Our studies confirmed that loss-of-function of NOX1 causes abrogated ROS activity, but they also provided novel mechanistic insights into human NOX1 deficiency. Cells that were NOX1-mutant showed impaired wound healing and attenuated 2-dimensional collective chemotactic migration. High-resolution microscopy of the migrating cell edge revealed a reduced density of filopodial protrusions with altered focal adhesions in NOX1-deficient cells, accompanied by reduced phosphorylation of p190A. Assessment of single-cell planktonic migration toward an epidermal growth factor gradient showed that NOX1 deficiency is associated with altered migration dynamics with loss of directionality and altered cell-cell interactions.

Conclusions
Our studies on pediatric-onset IBD patients with a rare sequence variant in NOX1 highlight that human NOX1 is involved in regulating wound healing by altering epithelial cytoskeletal dynamics at the leading edge and directing cell migration.
Intersections of machine learning and epidemiological methods for health services research
Authors: Rose Sherri 
Published: February 2020

AbstractThe field of health services research is broad and seeks to answer questions about the health care system. It is inherently interdisciplinary, and epidemiologists have made crucial contributions. Parametric regression techniques remain standard practice in health services research with machine learning techniques currently having low penetrance in comparison. However, studies in several prominent areas, including health care spending, outcomes and quality, have begun deploying machine learning tools for these applications. Nevertheless, major advances in epidemiological methods are also as yet underleveraged in health services research. This article summarizes the current state of machine learning in key areas of health services research, and discusses important future directions at the intersection of machine learning and epidemiological methods for health services research.
Summer Outbreak of Severe RSV-B Disease, Minnesota, 2017 Associated with Emergence of a Genetically Distinct Viral Lineage
Authors: Thielen Beth K , Bye Erica , Wang Xiong , Maroushek Stacene , Friedlander Hannah , Bistodeau Sarah , Christensen Jaime , Reisdorf Erik , Shilts Meghan H , Martin Karen , Como-Sabetti Kathryn , Strain Anna K , Ferrieri Patricia , Lynfield Ruth 
Published: February 2020

Abstract

Background
Respiratory syncytial virus (RSV) typically causes winter outbreaks in temperate climates. During summer 2017, the Minnesota Department of Health received a report of increased cases of severe RSV-B infection.

Methods
We compared characteristics of summer 2017 cases with those of 2014–2018 summers. To understand the genetic relatedness among viruses, we performed high-throughput sequencing of RSV from patients with a spectrum of illness from sites in Minnesota and Wisconsin.

Results
From May to September 2017, 58 RSV cases (43 RSV-B) were reported compared to 20–29 cases (3–7 RSV-B) during these months in other years. Median age and frequency of comorbidities were similar, but 55% (24/43) were admitted to the ICU in 2017 compared to 12% in preceding 3 years (odds ratio, 4.84, P &lt; .01). Sequencing was performed on 137 specimens from March 2016 to March 2018. Outbreak cases formed a unique clade sharing a single conserved nonsynonymous change in the SH gene. We observed increased cases during the following winter season, when the new lineage was the predominant strain.

Conclusions
We identified an outbreak of severe RSV-B disease associated with a new genetic lineage among urban Minnesota children during a time of expected low RSV circulation.