bluuebunny/crossref_metadata_2025 huggingface dataset:
The “scar” of a pandemic: Cumulative incidence of COVID‐19 during the first trimester of pregnancy
Authors: Cosma Stefano , Borella Fulvio , Carosso Andrea , Sciarrone Andrea , Cusato Jessica , Corcione Silvia , Mengozzi Giulio , Preti Mario , Katsaros Dionyssios , Di Perri Giovanni , Benedetto Chiara
Published: July 2020

Congenitally‐ or perinatally‐acquired viral infections can be harmful to the fetus but data are limited about prevalence and outcomes of coronavirus disease 2019 (COVID‐19) disease during the first trimester of pregnancy. We report epidemiologic data from a study investigating a cohort of women who became pregnant just before or during the COVID‐19 pandemic. We recruited 138 consecutive pregnant women attending for first trimester screening (11‐13 weeks of gestation) at Sant'Anna Hospital, Turin, Piedmont, Italy, during the plateau and the falling phase of the COVID‐19 epidemic curve. Patients were tested for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immunoglobulin M/immunoglobulin G antibody levels and SARS‐CoV‐2 detection in sera and nasopharyngeal swab samples. COVID‐19 cumulative incidence during the first trimester was of 10.1% with high prevalence of asymptomatic patients (42.8%). Similar to the course of the disease in non pregnant adults, 80% to 90% of infections were not severe.The prevalence of reported symptoms was four‐fold higher in SARS‐CoV‐2 positive patients (57%) than in those negative (13%) (P < .001), suggesting that direct self‐testing should open doors to confirmatory testing for COVID‐19. Our findings support the need for COVID‐19 screening in early pregnancy in epidemic areas to plan materno‐fetal health surveillance programs.
Mental Health as Ruination: The Psychiatrization of Space and Poverty in Seattle
Authors: Marlovits John
Published: July 2020

This essay draws on ethnographic research I conducted in “clubhouse” spaces in two community mental health clinics serving economically disadvantaged people of color and immigrants in Seattle. Drawing on my informants’ experiences in the Pioneer Square neighborhood—an enclave associated with the “homeless mentally ill”—and in mental health clinics, I track the displacement and containment of a “right to the city” for impoverished people. I track the notion of the homeless mentally ill as a figure of postwar psychiatric discourse through its history in Seattle, arguing that postwar American psychiatry and community mental health recoded poverty as a question of madness, transforming the material needs and the rights of citizenship of the poor into questions of “character reform” and therapeutic services. I suggest that the imagination of Pioneer Square and the deprivation my informants experienced in mental health clinics is not a side effect of clinical “mismanagement” but rather part of an ongoing practice of what Ann Stoler calls “ruination,” ritualized indignities embedded in the paternalistic separation of the material and the therapeutic in postwar American psychiatry. Ultimately I address questions of poverty, home, and rights to space in Seattle.
Exploring the effect of problem‐based facilitatory teaching approach on metacognition in nursing education: A quasi‐experimental study of nurse students in Tanzania
Authors: Millanzi Walter C. , Kibusi Stephen M.
Published: July 2020

Aim

Currently, there has been a progressive shortage of not only the number of frontline healthcare providers but also a decline in the quality of nursing care. There is a growing concern to rethink the approaches on how nurses are prepared, explore and test novel approaches for delivering the nursing curricula. This study tested the effect of the problem‐based facilitatory teaching approach on metacognition among nursing students in Tanzania, higher learning institutions.

Design

A controlled pre‐/post‐test quasi‐experimental study design with a quantitative research approach was employed in this study.

Methods

The study was conducted between February–June 2019 including two purposively selected higher learning institutions in the Dodoma region, the central zone of Tanzania. The 401 randomly selected undergraduate nursing students (interventional = 134 and control = 267) were involved. The auditing inventory developed by the researcher measured the intervention, and the questionnaire titled Metacognition Strategies in Nursing was adopted to measure the metacognition, respectively. Statistical analysis was performed using the Statistical Package for the Social Solution (SPSS) software program version 23.

Results

Findings indicated that 65.8% of the study participants were males. The post‐test findings revealed a significant gain in metacognition scores among participants in an intervention group between (M = 23.27; SD = 1.716) at baseline and (M = 66.31; SD = 6.204) post‐intervention. 63.4% of the total sample in an intervention group demonstrated a high level of knowledge about the regulation of cognition compared to their counterpart control group. However, 69.1% (N = 85) participants in the control group performed better for the knowledge about cognition. With the control of other factors, the intervention was found to be more times likely to influence metacognition among nurse students (AOR = 1.603, p < 0.05, 95% CI: 1.023, 2.513) . In conclusion, the intervention had the potential to positively effect the levels of metacognition among nurse students. Hence, it was closely linked to professional competency and it would change the spectrum of nursing competency and quality of care among nurse students.
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

This 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

Efficient 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 Statement

Recombinase‐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

Rationale

Oxygen (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.

Methods

We 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.

Results

In 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.

Conclusions

This 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

Rationale

Over 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).

Methods

α‐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.

Results

Matrix 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.

Conclusions

We 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

Rationale

Eomecon 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.

Methods

A 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.

Results

Ultrahigh‐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.

Conclusions

This 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

Purpose

In 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.

Methods

In 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.

Results

There 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.

Conclusions

Medium 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

Noncoding 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
The Triclinic Lanthanoid(III) Halide Oxidoarsenates(III) Sm3Cl2[As2O5][AsO3] and Tm3Br2[As2O5][AsO3]
Authors: Goerigk Felix C. , Schander Svetlana , Wickleder Mathias S. , Schleid Thomas
Published: July 2020

Pale yellow single crystals of the composition Ln3X2[As2O5][AsO3] (Ln = Tm for X = Br and Ln = Sm for X = Cl) were obtained via solid‐state reactions in the systems Ln2O3/As2O3 from sealed silica ampoules using different halides as fluxing agents. Sm3Cl2[As2O5][AsO3] and Tm3Br2[As2O5][AsO3] crystallize isotypically in the triclinic space group P1 with Z = 2 and cell parameters of a = 543.51(4) pm, b = 837.24(6) pm, c = 1113.45(8) pm, α = 90.084(2)°, β = 94.532(2)°, γ = 90.487(2)° for the samarium and a = 534.96(4) pm, b = 869.26(6) pm, c = 1081.84(8) pm, α = 90.723(2)°, β = 94.792(2)° γ = 90.119(2)° for the thulium compound. The isotypic crystal structure of both representatives exhibits three crystallographically different Ln3+ cations, each with a coordination number of eight. (Ln1)3+ and (Ln2)3+ are only coordinated by three oxygen atoms, whereas (Ln3)3+ shows additional contacts to halide anions in forming square [LnO4X4]9– antiprisms. All As3+ cations are surrounded by three oxygen atoms in the shape of isolated [AsO3]3– ψ1‐tetrahedra. They occur either isolated or condensed as pyroanionic [As2O5]4– units with a bridging oxygen atom. In both anions, non‐binding lone‐pair electrons are present at the As3+ cations with a pronounced stereochemically active function.
A Methylated Oxo‐Thio Stannate Cluster from a Non‐Innocent Ionic Liquid
Authors: Peters Bertram , Reith Sascha , Dehnen Stefanie
Published: July 2020

A new salt of the alkylated oxo‐thio stannate cluster [Sn10O4S16(SMe)4]4–, (C4C4C1Im)4[Sn10O4S16(SMe)4] (1), was obtained by ionothermal treatment of K4[SnS4]·4H2O. The reaction was carried out in the ionic liquid 1,3‐dibutyl‐2‐methylimidazolium chloride, (C4C4C1Im)Cl, which proved to be non‐innocent against the chalcogenido metallate species in the reaction mixture. In continuation of our first studies on alkylation of very weakly nucleophilic chalcogenido metalate anions, this study served to prove that an N‐bonded alkyl group is selectively released from the imidazolium cation of the ionic liquid, and it served to show that methylation is favored over butylation. The title compound is one of the rare cases, in which the cations of the salt, which stem from the ionic liquid, could be crystallographically determined without problems.
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

Dystonia 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

Comorbidities 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

Heart 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

Desmosomal 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

Identifying 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

Deep 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.
The problem of shelf-warmers in electronic commerce: a proposed solution
Authors: Chodak Grzegorz
Published: July 2020

This paper presents the significant problem of so called shelf-warmers in the environment of electronic commerce. In the first part of the paper, the factors that have led to an increasing stock of shelf-warmers in online stores are discussed. These factors are divided into two groups: those that occur mainly in an online store environment and those not specifically associated with an online environment. One group of factors are related to the large number of items offered in an online store enabled by various models of inventory management (e.g. drop-shipping, 3PL, 4PL), the lack of a need to maintain costly space for the exposition of goods, the heterogeneity of online shoppers and the large number of returns from customers. The other group of factors concern incorrect forecasts of demand, inappropriate inventory control, choice of product assortment, pricing policies and the end of a product’s life cycle. The problem of appropriately identifying shelf-warmers is then discussed and an index measuring the tendency of a good to be a shelf-warmer is proposed. Based on this, different methods for dealing with shelf-warmers are outlined in the form of the use of recommendation systems, search engine optimization and social media. The paper then presents an experiment conducted in a real business environment to assess the effectiveness of some of the aforementioned methods. This experiment resulted in the sale of approximately 33% of 160 selected shelf-warmers and over 50% from one group (number 8) where all the suggestions were implemented, within a period of 10 months. The results obtained show that the methods and recommendations proposed may help online stores to deal with the problem of shelf-warmers.
Cohomogeneity one Alexandrov spaces in low dimensions
Authors: Galaz-García Fernando , Zarei Masoumeh
Published: July 2020

Alexandrov spaces are complete length spaces with a lower curvature bound in the triangle comparison sense. When they are equipped with an effective isometric action of a compact Lie group with one-dimensional orbit space, they are said to be of cohomogeneity one. Well-known examples include cohomogeneity-one Riemannian manifolds with a uniform lower sectional curvature bound; such spaces are of interest in the context of non-negative and positive sectional curvature. In the present article we classify closed, simply connected cohomogeneity-one Alexandrov spaces in dimensions 5, 6 and 7. This yields, in combination with previous results for manifolds and Alexandrov spaces, a complete classification of closed, simply connected cohomogeneity-one Alexandrov spaces in dimensions at most 7.
Correction to: Bottom mixed layer oxygen dynamics in the Celtic Sea
Authors: Hull Tom , Johnson Martin , Greenwood Naomi , Kaiser Jan
Published: July 2020

The initial online publication contained several typesetting errors. The original article has been corrected.
Genetic mutation profile of Chinese HER2-positive breast cancers and genetic predictors of responses to Neoadjuvant anti-HER2 therapy
Authors: Li Kai , Liao Ning , Chen Bo , Zhang Guochun , Wang Yulei , Guo Liping , Wei Guangnan , Jia Minghan , Wen Lingzhu , Ren Chongyang , Cao Li , Mok Hsiaopei , Li Cheukfai , Lin Jiali , Chen Xiaoqing , Zhang Zhou , Hou Ting , Li Min , Liu Jing , Balch Charles M. , Liao Ning
Published: July 2020

Purpose

Despite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses.

Methods

We employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People’s Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0).

Results

In Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366–36.749, p = 0.020 and OR 6.007, 95% CI 1.120–32.210, p = 0.036, respectively) were found to be predictive of pCR status.

Conclusion

TP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.
The Supervision of Guilty Pleas by the Court of Appeal of England and Wales – Workable Relationships and Tragic Choices
Authors: Nobles Richard , Schiff David
Published: July 2020

The judgments of criminal appeal courts are an example of Calabresi and Bobbitt’s concept of ‘tragic choice’. Judges justify convictions by reference to the values which they attribute to criminal procedures: fairness, truth and rights, rather than the full range of considerations which have influenced the introduction of those procedures: cost, efficiency, crime control, public perceptions of crime, etc. The difficulties facing the Court of Appeal in justifying convictions by juries after a full trial are multiplied in the case of convictions following guilty pleas. A procedure which on its face is less capable of identifying guilt than a trial, has to be defended on the basis that it is overwhelmingly more capable of identifying guilt (or so fair as to justify disregarding the possibility of innocence). Recent changes to the plea system restricting maximum sentence discounts to pleas made at the earliest opportunity further distance guilty pleas from the protections afforded by trial, and compound the difficulties in justifying these convictions as ‘safe’. With guilty pleas we have reached a situation where the Court of Appeal seems unable to provide a remedy for miscarriages, but instead, like the judges of the 19th century opposing the creation of the Criminal Court of Appeal, claims the procedure is so safe that there is little or no need for review, even in cases of procedural irregularity (short of abuse of process) or new evidence (short of exoneration).
Geogenic and anthropogenic interactions at a former Sb mine: environmental impacts of As and Sb
Authors: Mbadugha Lenka , Cowper Duncan , Dossanov Sapar , Paton Graeme I.
Published: July 2020

Mining activities are acknowledged to introduce contaminants into localised environments and cause wider spread diffuse pollution. The concentration, distribution and fate of arsenic (As) and antimony (Sb) were studied at the former metalliferous Louisa Mine at Glendinning, Scotland. Soils and surface water were sampled and subsequently analysed to map the distribution of contamination and identify pollution sources. The maximum concentrations of As and Sb of 15,490 and 1504.2 mg kg−1, respectively, were determined in soils associated with the ore processing area and spoil heaps. The fractions of dissolved As and Sb in soils were < 1 and < 5% of total soil content, respectively, confirming findings of previous studies that As and Sb are relatively immobile. Yet, the concentrations of As and Sb released by soils exceeded regulatory limits. Concentrations of As and Sb in surface water in the immediate vicinity of the mine were impacted by a gully discharge, but rapidly diluted. While the concentrations affected by the run-off waters did not exceed EU environmental standards for freshwater, the concentrations of both, As and Sb, sharply increased above the said environmental standards approximately 100 m downstream of the mine site. The unaltered As-to-Sb ratio in water samples suggests a geogenic source. While there is a justifiable concern about the soil pollution caused by the historic mining in the area, the Glenshanna Burn is affected more by indigenous geochemical processes than the derelict mine.
Distinct microalgae species for food—part 2: comparative life cycle assessment of microalgae and fish for eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and protein
Authors: Schade S. , Stangl G. I. , Meier T.
Published: July 2020

The production of food for a growing world population is a great challenge. In particular, protein and the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), which exert a series of potential health effects, are scarce resources in the context of global food security. Fish from wild capture and aquaculture production cannot meet the current demand for EPA and DHA; therefore, a supplementation with alternative sources is crucial. Specific microalgae species have been shown to be a lucrative source of EPA, DHA, and protein, in particular, the oleaginous microalgae Nannochloropsis sp. and Phaeodactylum tricornutum. This study aimed to compare different cultivation scenarios of Nannochloropsis sp. and P. tricornutum with the production of aquaculture and capture fish as traditional sources of EPA and DHA in terms of environmental impacts. Scenarios included borosilicate glass and acrylic glass as photobioreactor (PBR) materials, two different tube diameters, and three different cultivation seasons. In these scenarios, carbon dioxide was modeled as an avoided burden. Additionally, all scenarios were modeled with the burdens resulting from carbon dioxide production. Environmental impacts of selected fish species were obtained from systematic literature research. Life cycle assessment following ISO 14040/44 was used to analyze the global warming potential, acidification, eutrophication, cumulative energy demand, water footprint, and land use. The system boundaries were set from “cradle-to-store,” where the target store is located in Germany. Microalgae biomass as a source of EPA, DHA, and protein was found to have similar or lower environmental impacts than fish fillet from wild capture and aquaculture production when carbon dioxide was modeled as an avoided burden. Microalgae production that included the full burden of carbon dioxide production still caused similar or lower environmental impacts than aquaculture fish. It was found that the distinct microalgae species can significantly influence the results if the comparison is conducted based on nutritional values. Regarding the recommended daily intake of 250–500 mg EPA+DHA, microalgae are an advisable source of nutrients to lessen the environmental pressure on marine ecosystems.
CcpNmr AnalysisScreen, a new software programme with dedicated automated analysis tools for fragment-based drug discovery by NMR
Authors: Mureddu Luca G. , Ragan Timothy J. , Brooksbank Edward J. , Vuister Geerten W.
Published: July 2020

Fragment-based drug discovery or FBDD is one of the main methods used by industry and academia for identifying drug-like candidates in early stages of drug discovery. NMR has a significant impact at any stage of the drug discovery process, from primary identification of small molecules to the elucidation of binding modes for guiding optimisations. The essence of NMR as an analytical tool, however, requires the processing and analysis of relatively large amounts of single data items, e.g. spectra, which can be daunting when managed manually. One bottleneck in FBDD by NMR is a lack of adequate and well-integrated resources for NMR data analysis that are freely available to the community. Thus, scientists typically resort to manually inspecting large datasets and relying predominantly on subjective interpretations. In this manuscript, we present CcpNmr AnalysisScreen, a software package that provides computational tools for automated analysis of FBDD data by NMR. We outline how the quality of collected spectra can be evaluated quickly, and how robust workflows can be optimised for reliable and rapid hit identification. With an intuitive graphical user interface and powerful algorithms, AnalysisScreen enables easy analysis of the large datasets needed in the early process of drug discovery by NMR.
Fidgeting Behavior During Psychotherapy: Hand Movement Structure Contains Information About Depressive Symptoms
Authors: Reinecke Katharina C. H. , Dvoretska Daniela , Joraschky Peter , Lausberg Hedda
Published: July 2020

Fidgeting may be a motor sign reflecting self-regulation processes in patients with social anxiety disorder (SAD) and depressive patients. Since SAD co-occurs with comorbid depression, the question arises whether fidgeting is a disorder-unspecific phenomenon or a specific and therefore diagnostically relevant sign of depression. 33 SAD patients with (n = 12) and without (n = 21) depression from the Social Phobia Psychotherapy Research Network project were compared regarding their nonverbal behavior. Four video sequences of a psychotherapy session with each patient were analyzed using a standardized system for the analysis of nonverbal behavior by two independent, certified, blind raters. SAD patients with comorbid depression exhibited significantly more (number/minute) irregular movements, but fewer (number/minute) repetitive movements than SAD patients without depression. Irregular movements, which reflect less structured motor behavior, are associated with comorbid depression in SAD. In contrast, in SAD without depression, more structured repetitive movements were prominent. Thus, irregular movements represent a diagnostically relevant behavior for comorbid depression among SAD patients.
Impacts of a Home Visiting Program Enhanced with Content on Healthy Birth Spacing
Authors: Zief Susan , Deke John , Burkander Paul , Langan Andrew , Asheer Subuhi
Published: July 2020

Objectives

This study sought to determine the impact of Healthy Families Healthy Futures (HFHF) enhanced with Steps to Success (STS). HFHF is a structured home visiting program for teen parents in Houston that focuses on improving parenting skills and preventing child abuse. HFHF enhanced with STS includes content and activities aimed to reduce repeat pregnancies within 24 months after the first child’s birth.

Methods

The study team recruited 248 young mothers for the study, primarily through local health clinics and schools, and then randomly assigned them to either a treatment group that was eligible to participate in HFHF enhanced with STS or to a control group. The control group was not offered any other program through the study. Outcomes were measured by a survey administered 12 months after program intake, in five domains aligned with the program’s logic model: (1) exposure to information related to program content, (2) contraception knowledge, (3) contraception use, (4) enhanced family functioning, and (5) child health and development. To estimate program impacts, we used ordinary least squares regression, controlling for demographics and baseline measures of the outcome variables, if available. We use both frequentist approaches (calculations of statistical significance) and Bayesian posterior probabilities to interpret the findings.

Results

HFHF enhanced with STS significantly (p < .05) impacted exposure to information on parenting and birth control, with effects of 20.8 and 15.4 percentage points, respectively. Using Bayesian posterior probabilities, there is an 85% chance that the program had a favorable effect on these outcomes. We also calculate a probability of 77% that the program had a favorable impact on long-acting reversible contraceptive (LARC) use, but a probability of 89% that the program reduced knowledge of birth control pills; these two results were not statistically significant (p = .17 and .10, respectively).

Conclusions for Practice

These findings are primarily favorable and consistent with the program content and goals. Smaller than anticipated sample sizes due to recruitment challenges increased the chances for random error to affect the ability to detect statistically significant differences on many of our other outcomes; Bayesian posterior probabilities can therefore aid in interpreting the impact estimates. More research of this promising model is warranted.