bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigation of increased rates of autism in U.S. public schools
Authors: Cardinal Donald N. , Griffiths Amy Jane , Maupin Zachary D. , Fraumeni‐McBride Julie 
Published: July 2020

AbstractThis study is intended to enhance our understanding of the dramatic increase in autism prevalence rates across the United States. A robust national and multistate sample of children and youth (5–22 years of age) was gathered and analyzed, using visual and statistical analysis of autism eligibility over a 15‐ to 17‐year period. Although the impact of environmental or genetic influences cannot be entirely ruled out, we identified significant shifts in eligibility trends that substantially contribute to the remarkable increase in autism prevalence. Assessment procedures and criteria for autism have sustained an indelible influence from this diagnostic migration, which has had a lasting impact on public schools. We use this information to provide meaningful implications for practicing psychology in the schools.
Recombinase‐mediated integration of a multigene cassette in rice leads to stable expression and inheritance of the stacked locus
Authors: Pathak Bhuvan , Srivastava Vibha 
Published: July 2020

AbstractEfficient methods for multigene transformation are important for developing novel crop varieties. Methods based on random integrations of multiple genes have been successfully used for metabolic engineering in plants. However, efficiency of co‐integration and co‐expression of the genes could present a bottleneck. Recombinase‐mediated integration into the engineered target sites is arguably a more efficient method of targeted integration that leads to the generation of stable transgenic lines at a high rate. This method has the potential to streamline multigene transformation for metabolic engineering and trait stacking in plants. Therefore, empirical testing of transgene(s) stability from the multigene site‐specific integration locus is needed. Here, the recombinase technology based on Cre‐lox recombination was evaluated for developing multigenic lines harboring constitutively‐expressed and inducible genes. Targeted integration of a five genes cassette in the rice genome generated a precise full‐length integration of the cassette at a high rate, and the resulting multigenic lines expressed each gene reliably as defined by their promoter activity. The stable constitutive or inducible expression was faithfully transmitted to the progeny, indicating inheritance‐stability of the multigene locus. Co‐localization of two distinctly inducible genes by heat or cold with the strongly constitutive genes did not appear to interfere with each other's expression pattern. In summary, high rate of co‐integration and co‐expression of the multigene cassette installed by the recombinase technology in rice shows that this approach is appropriate for multigene transformation and introduction of co‐segregating traits.Significance StatementRecombinase‐mediated site‐specific integration approach was found to be highly efficacious in multigene transformation of rice showing proper regulation of each gene driven by constitutive or inducible promoter. This approach holds promise for streamlining gene stacking in crops and expressing complex multigenic traits.
High‐precision stable isotope analysis of <5 μg CaCO3 samples by continuous‐flow mass spectrometry
Authors: Vonhof Hubert B. , de Graaf Stefan , Spero Howard J. , Schiebel Ralf , Verdegaal Suzan J.A. , Metcalfe Brett , Haug Gerald H. 
Published: July 2020

RationaleOxygen (δ18O) and carbon (δ13C) isotope analysis of foraminifera and other CaCO3 samples has been a key technique for paleoceanographical and paleoclimatological research for more than 60 years. There is ongoing demand for the analysis of ever smaller CaCO3 samples, driven, for example, by the desire to analyse single specimen planktic foraminifera, or small samples of tooth enamel.MethodsWe present a continuous‐flow mass spectrometric technique that uses cryo‐focusing of sample CO2 to analyse CaCO3 samples in a weight range between 10 and 3 μg. These are considerably lower sample weights than achievable on most currently available standard instrumentation. The technique is automated, so that sample throughput lies at >60 samples per day. The method involves an on‐line vial‐flushing routine designed to remove machine drift due to blank CO2 build‐up in the sample vials.ResultsIn a series of experiments the effect of blank CO2 build‐up is quantified, and outgassing from the chlorobutyl septa identified as the source. An improved flushing routine together with the use of a cryo‐focusing step in the analysis is demonstrated to provide the analytical stability and sensitivity to analyse CaCO3 samples in a weight range between 10 and 3 μg at ≤0.1‰ precision (1σ) for both δ18O and δ13C values. The technique yields similarly precise results for the analysis of the structural carbonate fraction of small tooth enamel samples.ConclusionsThis study demonstrates that high‐precision oxygen and carbon isotope analysis is possible on CaCO3 samples smaller than 5 μg by use of a continuous‐flow isotope technique. Of key importance are (1) the application of a cold trap that drastically reduces sample gas loss, and (2) a modified flushing regime that eliminates increasing background CO2 build‐up in sample vials during longer automated sample runs.
Novel methods for the analysis of toxicants in bronchoalveolar lavage fluid samples from e‐cigarette, or vaping, product use associated lung injury (EVALI) cases: Terpenes
Authors: De Jesús Víctor R. , Silva Lalith K. , Newman Cody A. , Blount Benjamin C. 
Published: July 2020

RationaleOver 2800 e‐cigarette, or vaping, product use‐associated lung injury (EVALI) cases were reported to the Centers for Disease Control and Prevention (CDC) during August 2019 to February 2020. Bronchoalveolar lavage (BAL) fluid samples from 51 EVALI and 99 non‐EVALI cases were analyzed for toxicants including terpenes. We describe a novel method to measure selected terpenes in BAL fluid by gas chromatography/tandem mass spectrometry (GC/MS/MS).Methodsα‐Pinene, β‐pinene, β‐myrcene, 3‐carene, and limonene were measured in BAL fluid specimens by headspace solid‐phase microextraction/gas chromatography/tandem mass spectrometry. We created and characterized BAL fluid pools from non‐EVALI individuals to determine assay accuracy, precision, linearity, limits of detection, and analytical specificity. All measurements were conducted in accordance with the CDC's Division of Laboratory Sciences rigorous method validation procedures.ResultsMatrix validation experiments showed that calibration curves in BAL fluid and saline had similar slopes, with differences of less than 7%. The assay precision ranged from 2.52% to 5.30%. In addition, the limits of detection for the five analytes ranged from 1.80 to 16.8 ng/L, and the linearity was confirmed with R2 values >0.99.ConclusionsWe developed and validated a method to quantify selected terpenes in BAL fluid specimens using GC/MS/MS. The assay provided accurate and precise analyses of EVALI and non‐EVALI BAL fluid specimens in support of CDC's EVALI response. This method is applicable to the determination of a broad range of terpenes in BAL fluid specimens.
Systematic characterization of alkaloids in Eomecon chionantha Hance using ultrahigh‐performance liquid chromatography–tandem quadrupole Exactive Orbitrap mass spectrometry with a four‐step screening strategy
Authors: Lu Meilong , Li Ke , He Hailang , Cheng Yating , Yang Peng 
Published: July 2020

RationaleEomecon chionantha Hance (ECH), a traditional folk herb, is commonly used to treat traumatic injuries based on its analgesic and anti‐inflammatory properties. Previous studies have reported that alkaloids are the major bioactive components in ECH. Therefore, identification of alkaloids from ECH contributes to the discovery of its potential active ingredients and quality control in clinic treatments.MethodsA four‐step screening strategy was performed as follows. (1) Extracting the accurate masses of ions related to different molecules. (2) Screening different types of compounds using their molecular cations, protonated molecules, diagnostic product ions and fragmentation pathways. (3) Comparing the characteristic product ion formulae to obtain the type and number of substituents. (4) Using the biosynthetic pathways of isoquinoline alkaloids to determine the concentration of alkaloids.ResultsUltrahigh‐performance liquid chromatography–tandem quadrupole Exactive Orbitrap mass spectrometry (UHPLC/Q‐Exactive Orbitrap MS) analysis combined with the four‐step screening strategy was used to profile the alkaloids in ECH. The structures of 95 alkaloids in ECH were unambiguously identified or reasonably assigned, of which 76 were reported in ECH for the first time. Six types of benzylisoquinoline alkaloids were identified in ECH: six benzyltetrahydroisoquinolines, nine protopines, five N‐methyltetrahydroprotoberberines, six protoberberines, eight benzophenanthridines and sixty‐one dihydrobenzophenanthridines.ConclusionsThis comprehensive study identified the alkaloids in ECH, thus providing a practical reference for further research. The UHPLC/Q‐Exactive Orbitrap MS method, combined with the four‐step screening strategy, which was developed and successfully applied to identify the alkaloids in ECH, may also be applicable for the efficient screening of other herbal medicines.
Usefulness of modified Medium RD as a chemically defined medium for in vitro maturation of bovine oocytes
Authors: Momozawa Kenji 
Published: July 2020

AbstractPurposeIn the present study, I evaluated the usefulness of Medium RD, with mixed RPMI1640 and Dulbecco's modified Eagle's medium (1:1, v/v), as a chemically defined medium for in vitro maturation (IVM) of bovine oocytes.MethodsIn vitro maturation was performed in 10 mmol/L HEPES‐buffered TCM199 (mTCM199), 10 mmol/L HEPES‐buffered Medium RD (mRD), and mTCM199 supplemented with fetal bovine serum fraction (mTCM199 + FBS fraction) that served as control. Cumulus‐oocyte complexes were matured for 24 hours in three different media supplemented with follicle‐stimulating hormone, estradiol‐17β, and polyvinylpyrrolidone. Nuclear maturation of oocytes, their developmental competence into blastocysts after in vitro fertilization (IVF) and mitochondrial distribution in oocytes were investigated.ResultsThere was no difference in the ratio of matured oocytes regardless of IVM media. The percentage of morula stage was higher in mRD than in mTCM199 group (P < .05) at 120‐144 hours after IVF, although the blastocyst rates between groups were not significantly different at 168‐216 hours. IVM in mRD increased the percentage of oocytes with diffused mitochondrial distribution compared with the immature and mTCM199 and had similar percentage of oocytes in mTCM199 + FBS fraction.ConclusionsMedium RD would be useful as a chemically defined medium for IVM of bovine oocytes.
Two sides of the same medal: Noncoding mutations reveal new pathological mechanisms and insights into the regulation of gene expression
Authors: Wachs Amelie S. , Bohne Jens 
Published: July 2020

AbstractNoncoding sequences constitute the major part of the human genome and also of pre‐mRNAs. Single nucleotide variants in these regions are often overlooked, but may be responsible for much of the variation of phenotypes observed. Mutations in the noncoding part of pre‐mRNAs often reveal new and meaningful insights into the regulation of cellular gene expression. Thus, the mechanistic analysis of the pathological mechanism of such mutations will both foster a deeper understanding of the disease and the underlying cellular pathways. Even synonymous mutations can cause diseases, since the primary mRNA sequence not only encodes amino acids, but also encrypts information on RNA‐binding proteins and secondary structure. In fact, the RNA sequence directs assembly of a specific mRNP complex, which in turn dictates the fate of the mRNA or regulates its biogenesis. The accumulation of genomic sequence information is increasing at a rapid pace. However, much of the diversity uncovered may not explain the phenotype of a certain syndrome or disease. For this reason, we also emphasize the value of mechanistic studies on pathological mechanisms being complementary to genome‐wide studies and bioinformatic approaches.This article is categorized under:
RNA Processing > Splicing Regulation/Alternative Splicing
RNA Processing > 3′ End Processing
RNA in Disease and Development > RNA in Disease
3d $$ \mathcal{N} $$ = 4 OPE coefficients from Fermi gas
Authors: Chester Shai M. , Kalloor Rohit R. , Sharon Adar 
Published: July 2020

Abstract
The partition function of a 3d $$ \mathcal{N} $$
N
= 4 gauge theory with rank N can be computed using supersymmetric localization in terms of a matrix model, which often can be formulated as an ideal Fermi gas with a non-trivial one-particle Hamiltonian. We show how OPE coefficients of protected operators correspond in this formalism to averages of n-body operators in the Fermi gas, which can be computed to all orders in 1/N using the WKB expansion. We use this formalism to compute OPE coefficients in the U(N)k× U(N)−k ABJM theory as well as the U(N ) theory with one adjoint and Nf fundamental hypermultiplets, both of which have weakly coupled M-theory duals in the large N and finite k or Nf regimes. For ABJM we reproduce known results, while for the Nf theory we compute the all orders in 1/N dependence at finite Nf for the coefficient cT of the stress tensor two-point function.
Neurophysiological insights in dystonia and its response to deep brain stimulation treatment
Authors: Tisch Stephen , Limousin Patricia 
Published: July 2020

AbstractDystonia is a movement disorder characterised by involuntary muscle contractions resulting in abnormal movements, postures and tremor. The pathophysiology of dystonia is not fully understood but loss of neuronal inhibition, excessive sensorimotor plasticity and defective sensory processing are thought to contribute to network dysfunction underlying the disorder. Neurophysiology studies have been important in furthering our understanding of dystonia and have provided insights into the mechanism of effective dystonia treatment with pallidal deep brain stimulation. In this article we review neurophysiology studies in dystonia and its treatment with Deep Brain Stimulation, including Transcranial magnetic stimulation studies, studies of reflexes and sensory processing, and oscillatory activity recordings including local field potentials, micro-recordings, EEG and evoked potentials.
Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease
Authors: van de Wouw Jens , Sorop Oana , van Drie Ruben W. A. , van Duin Richard W. B. , Nguyen Isabel T. N. , Joles Jaap A. , Verhaar Marianne C. , Merkus Daphne , Duncker Dirk J. 
Published: July 2020

AbstractComorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial ‘Ischemia and No Obstructive Coronary Artery disease’ (INOCA). In the present study, we tested the hypothesis that CMD results in perturbations in myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities. DM (streptozotocin), HC (high-fat diet) and CKD (renal embolization) were induced in 10 female swine (DM + HC + CKD), while 12 healthy female swine on a normal diet served as controls (Normal). After 5 months, at a time when coronary atherosclerosis was still negligible, myocardial perfusion, metabolism, and function were studied at rest and during treadmill exercise. DM + HC + CKD animals showed hyperglycemia, hypercholesterolemia, and impaired kidney function. During exercise, DM + HC + CKD swine demonstrated perturbations in myocardial blood flow and oxygen delivery, necessitating a higher myocardial oxygen extraction—achieved despite reduced capillary density—resulting in lower coronary venous oxygen levels. Moreover, myocardial efficiency was lower, requiring higher oxygen consumption for a given level of myocardial work. These perturbations in myocardial oxygen balance were associated with lower myocardial lactate consumption, stroke volume, and LVdP/dtmax, suggestive of myocardial ischemia and dysfunction. Further analyses showed a reduction in adenosine-recruitable coronary flow reserve, but this was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained; the latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content. However, isolated small arteries displayed selective blunting of endothelium-dependent vasodilation in response to bradykinin in DM + HC + CKD swine, suggesting that changes in coronary microvascular function rather than in structure contributed to the perturbations in myocardial oxygen delivery. In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe enough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA.
CRISPLD1: a novel conserved target in the transition to human heart failure
Authors: Khadjeh Sara , Hindmarsh Vanessa , Weber Frederike , Cyganek Lukas , Vidal Ramon O. , Torkieh Setare , Streckfuss-Bömeke Katrin , Lbik Dawid , Tiburcy Malte , Mohamed Belal A. , Bonn Stefan , Toischer Karl , Hasenfuss Gerd 
Published: July 2020

AbstractHeart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca2+ regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions.
The inotropic agent digitoxin strengthens desmosomal adhesion in cardiac myocytes in an ERK1/2-dependent manner
Authors: Schinner Camilla , Olivares-Florez Silvana , Schlipp Angela , Trenz Sebastian , Feinendegen Manouk , Flaswinkel Heinrich , Kempf Ellen , Egu Desalegn Tadesse , Yeruva Sunil , Waschke Jens 
Published: July 2020

AbstractDesmosomal proteins are components of the intercalated disc and mediate cardiac myocyte adhesion. Enhancement of cardiac myocyte cohesion, referred to as “positive adhesiotropy”, was demonstrated to be a function of sympathetic signaling and to be relevant for a sufficient inotropic response. We used the inotropic agent digitoxin to investigate the link between inotropy and adhesiotropy. In contrast to wild-type hearts, digitoxin failed to enhance pulse pressure in perfused mice hearts lacking the desmosomal protein plakoglobin which was paralleled with abrogation of plaque thickening indicating that positive inotropic response requires intact desmosomal adhesion. Atomic force microscopy revealed that digitoxin increased the binding force of the adhesion molecule desmoglein-2 at cell–cell contact areas. This was paralleled by enhanced cardiac myocyte cohesion in both HL-1 cardiac myocytes and murine cardiac slices as determined by dissociation assays as well as by accumulation of desmosomal proteins at cell–cell contact areas. However, total protein levels or cytoskeletal anchorage were not affected. siRNA-mediated depletion of desmosomal proteins abrogated increase of cell cohesion demonstrating that intact desmosomal adhesion is required for positive adhesiotropy. Mechanistically, digitoxin caused activation of ERK1/2. In line with this, inhibition of ERK1/2 signaling abrogated the effects of digitoxin on cell–cell adhesion and desmosomal reorganization. These results show that the positive inotropic agent digitoxin enhances cardiac myocyte cohesion with reorganization of desmosomal proteins in an ERK1/2-dependent manner. Desmosomal adhesion seems to be important for a sufficient positive inotropic response of digitoxin treatment, which can be of medical relevance for the treatment of heart failure.
Disease gene discovery in male infertility: past, present and future
Authors: Xavier M. J. , Salas-Huetos A. , Oud M. S. , Aston K. I. , Veltman J. A. 
Published: July 2020

AbstractIdentifying the genes causing male infertility is important to increase our biological understanding as well as the diagnostic yield and clinical relevance of genetic testing in this disorder. While significant progress has been made in some areas, mainly in our knowledge of the genes underlying rare qualitative sperm defects, the same cannot be said for the genetics of quantitative sperm defects. Technological advances and approaches in genomics are critical for the process of disease gene identification. In this review we highlight the impact of various technological developments on male infertility gene discovery as well as functional validation, going from the past to the present and the future. In particular, we draw attention to the use of unbiased genomics approaches, the development of increasingly relevant functional assays and the importance of large-scale international collaboration to advance disease gene identification in male infertility.
Hilbert sEMG data scanning for hand gesture recognition based on deep learning
Authors: Tsinganos Panagiotis , Cornelis Bruno , Cornelis Jan , Jansen Bart , Skodras Athanassios 
Published: July 2020

AbstractDeep learning has transformed the field of data analysis by dramatically improving the state of the art in various classification and prediction tasks, especially in the area of computer vision. In biomedical engineering, a lot of new work is directed toward surface electromyography (sEMG)-based gesture recognition, often addressed as an image classification problem using convolutional neural networks (CNNs). In this paper, we utilize the Hilbert space-filling curve for the generation of image representations of sEMG signals, which allows the application of typical image processing pipelines such as CNNs on sequence data. The proposed method is evaluated on different state-of-the-art network architectures and yields a significant classification improvement over the approach without the Hilbert curve. Additionally, we develop a new network architecture (MSHilbNet) that takes advantage of multiple scales of an initial Hilbert curve representation and achieves equal performance with fewer convolutional layers.