bluuebunny/crossref_metadata_2025 huggingface dataset:
Eco-friendly approach to electro-mobility (Avangard approach)
Authors: Mirosław Marcin , Mirosław Tomasz , Deda Jakub , Zawadzki Adam
Published: June 2021

Electric vehicles are offered by many car companies. They are considered ecological, although in terms of power it depends on the energy system, in particular a source of power to charge cars. In case of the production version, and operation may be less or more for a wide meaning of environment. In the article, the authors will present the issues of ecological use of electric vehicles, comparing the combustion and electric environmental studies. An analysis of the common electric vehicle structures and their operation will be presented, in which the environmental performance of vehicles and their positive impact on the quality of life can be achieved or enhanced by a new approach to the design, production and servicing method [1-4]. Authors of final output products of production based on the concept of industry 4.0+ [5], where the final products are supplied by SMEs (Small and Medium Enterprises). The authors mention the business model [6] that stimulates the development of SME sales and the sharing of knowledge. In the described model of vehicle production, which can be extended to the manufacturing of small agricultural and municipal machines, new methods of design (using artificial intelligence) and production, including 3D printing and others, play an important role. The authors will present several technologies used in small-lot production and a forecast of their use.
Application of variable equivalent amplitude for determination of fatigue life of elements subjected to block loading
Authors: Obrał Justyna , Kurek Marta , Łagoda Tadeusz , Głowacka Karolina
Published: June 2021

This paper contains a proposition of a new method of determining the fatigue life of elements subjected to non-stationary loads. The model was based on the determination of the time-variable equivalent weighted amplitude. This amplitude is derived on a continuous basis as the arithmetic mean of nth root of the amplitudes that occur up to a given time. The analysis of the proposed model was carried out on the basis of selected literature insights based on specimens made of P91 and P92 steels. The experimental tests were performed under block loading with a zero mean value in the conditions of tension-compression with a small number of cycles.
Ingwer in der Phytotherapie
Authors: Neufeld Tanja , Pfuhlmann Katrin , Klose Petra , Langhorst Jost
Published: June 2021

Ingwer ist eine tropische Pflanze, welche im Wurzelstock 1,5–3%
ätherisches Öl enthält. Ingwer fördert die
Magenentleerung und den Magen-Darm-Transit und kann einen kurzfristigen Effekt
bei der Behandlung und Prävention von Übelkeit und Erbrechen
hervorrufen. Als in Pulverform anerkannte Arznei findet sie auch in der
Onkologie Verwendung. Es konnte gezeigt werden, dass Ingwer bei
Chemotherapie-induzierter Übelkeit/Erbrechen (CINV) behilflich
sein könnte. Es gibt Hinweise, dass höhere Ingwerdosen weniger
wirksam sind oder vorhandene Symptome verstärken können. Es
liegen erste Ergebnisse vor, dass die Tagesdosis von 1 g nicht
überschritten werden sollte. Weiterhin zeigte sich in einer Studie mit
fraglicher Qualität, dass mit Ingwer behandelte
Ovarialkarzinompatientinnen weniger Metastasen im Vergleich zur Kontrollgruppe
aufwiesen. Studien, welche den Einfluss von Ingwer auf die
Lebensqualität untersuchten, zeigen keine einheitlichen Ergebnisse.
Weitere qualitative hochwertige Studien sind nötig, um die medizinische
Wirksamkeit des Ingwers im onkologischen Kontext bestätigen und in der
Praxis etablieren zu können.
Ginseng – die Möglichkeit seiner Anwendung zur Behandlung der Tumor-assoziierten Müdigkeit
Authors: Pfuhlmann Katrin , Klose Petra , Neufeld Tanja , Langhorst Jost
Published: June 2021

Von dem zu den Efeugewächsen gehörigen Ginseng sind vor allem zwei Arten bekannt: Der Asiatische oder Koreanische Ginseng Panax ginseng und der Amerikanische Ginseng Panax quinquefolius. Anwendung finden Verarbeitungen der Ginsengwurzel (Ginseng Radix), welche etliche gesundheitsförderliche Inhaltsstoffe enthält. Die wichtigsten pharmakologisch aktiven Substanzen stellen die Ginsenoside dar. Ginseng gilt als traditionelles Mittel gegen Erschöpfungszustände aller Art. Für diesen Zweck ist der Asiatische Ginseng in Europa als Arzneimittel zugelassen. Ergebnisse hochwertiger randomisierter kontrollierter Studien zeigen erste positive Effekte der Anwendung von Ginseng bei Tumor-assoziierter Müdigkeit und liefern Hinweise für eine toxikologische Unbedenklichkeit des Ginsengs. Auf Grundlage dieser Publikationen wird in der S3-Leitlinie „Komplementärmedizin in der Behandlung von onkologischen PatientInnen“, welche gerade in der Konsultationsfassung vorliegt, über eine evidenzbasierte Empfehlung für die Anwendung von Ginseng bei Tumor-assoziierter Müdigkeit diskutiert. Eine belastbare Aussage hierüber wird in der final veröffentlichten Leitlinie vorliegen.
Herausforderung „Diabetesschulung“ in Pandemiezeiten
Authors: Fabisch Gottlobe
Published: June 2021

Vor gut einem Jahr lancierte der Verband der Diabetes-Beratungs- und Schulungsberufe in Deutschland e.V. (VDBD) über die Osterfeiertage eine Blitzumfrage unter seinen Mitgliedern. Ziel war es, zu erfahren, ob und wie eine Diabetesschulung für Patienten/innen in der Ausnahmesituation der aktuellen Pandemie überhaupt gelingen kann. Anfang April 2021 wiederholte der VDBD seine Blitzumfrage: Was hat sich in den letzten 12 Monaten aus Sicht der Diabetesschulungskräfte geändert?
Rheumatische Erkrankungen bei Diabetes mellitus
Authors: Wellstein Inga , Baerwald Christoph
Published: June 2021

Erkrankungen des Bewegungsapparats gehören zu den häufigsten Vorstellungsgründen in einer Hausarztpraxis. Wichtig ist in dem Zusammenhang ein frühzeitiges Erkennen und präventives Vorgehen zum Erhalt der Lebensqualität und Vermeidung von Morbidität. Ein Diabetes mellitus stellt für einige Erkrankungen einen wichtigen prädiktiven sowie verlaufsbestimmenden Faktor dar. Dieser Artikel zielt darauf ab, Ihnen das Wissen über die Erkrankungen und ihre Entstehung, praktische diagnostische Möglichkeiten sowie Therapieoptionen zu vermitteln und soll damit eine individuelle Behandlungsstrategie ermöglichen.
Mycobacterium setense isolated from a cat with atypical mycobacterial panniculitis
Authors: Apostolopoulos Neoklis , Prenger-Berninghoff Ellen , Wildermuth Brett , Moser Irmgard , Hillemann Doris , Nobach Daniel , Herden Christiane , Ewers Christa , Thom Nina
Published: June 2021

Bei einer Katze wurde eine atypische mykobakterielle Pannikulitis diagnostiziert. Mittels 16S-rRNA-Gen-Sequenzanalyse ließ sich Mycobacterium setense, ein grampositives stäbchenförmiges säurefestes Bakterium der Mycobacterium fortuitum-Gruppe nachweisen, das zuvor nie bei einem erkrankten Tier isoliert werden konnte. Initial wurden Resistenzen gegen Doxycyclin und Clarithromycin festgestellt und während der Behandlung mit Pradofloxacin entwickelte sich zudem eine Resistenz gegen Fluorchinolone, bedingt durch eine Mutation im Gyrasegen gyrA (S90W-Austausch). Trotz einer langfristigen antimikrobiellen Behandlung über 33 Monate wurde keine vollständige Heilung erzielt. Bei einer atypischen mykobakteriellen Pannikulitis ist die Speziesbestimmung mit Resistenztest die Grundlage für eine adäquate Antibiose.
Total Synthesis of Oxepin and Dihydrooxepin Containing Natural Products
Authors: Magauer Thomas , Sokol Kevin Rafael
Published: June 2021

The construction of oxepin and dihydrooxepin containing natural products represents a challenging task in total synthesis. In the last decades, a variety of synthetic methods have been reported for the installation of these structural motifs. Herein, we provide an overview of synthetic methods and strategies to construct these motifs in the context of natural product synthesis and highlight the key steps of each example.

1 Introduction

2 Oxepin Natural Products

3 Dihydrooxepin Natural Products

3 Brønsted or Lewis acid Catalyzed Cyclization

3.2 Radical Cyclization

3.3 Substitution and Addition Cyclization

3.4 Sigmatropic Rearrangement

3.5 Oxidative Methods

3.6 Transition Metal Catalyzed Cyclization

4 Summary
Perilesional Gliosis Is Associated with Outcome after Perinatal Stroke
Authors: Yu Sabrina , Lam Charissa , Shinde Siddharth , Kuczynski Andrea M. , Carlson Helen L. , Dukelow Sean P. , Brooks Brian L. , Kirton Adam
Published: June 2021

Perinatal ischemic stroke results in focal brain injury and life-long disability. Hemiplegic cerebral palsy and additional sequelae are common. With no prevention strategies, improving outcomes depends on understanding brain development. Reactive astrogliosis is a hallmark of brain injury that has been associated with outcomes but is unstudied in perinatal stroke. In this article, we hypothesized that gliosis was quantifiable and its extent would inversely correlate with clinical motor function. This was a population-based, retrospective, and cross-sectional study. Children with perinatal arterial ischemic stroke (AIS) or periventricular venous infarction (PVI) with magnetic resonance (MR) imaging were included. An image thresholding technique based on image intensity was utilized to quantify the degree of chronic gliosis on T2-weighted sequences. Gliosis scores were corrected for infarct volume and compared with the Assisting Hand and Melbourne Assessments (AHA and MA), neuropsychological profiles, and robotic measures. In total, 42 children were included: 25 with AIS and 17 with PVI (median = 14.0 years, range: 6.3–19 years, 63% males). Gliosis was quantifiable in all scans and scores were highly reliable. Gliosis scores as percentage of brain volume ranged from 0.3 to 3.2% and were comparable between stroke types. Higher gliosis scores were associated with better motor function for all three outcomes in the AIS group, but no association was observed for PVI. Gliosis can be objectively quantified in children with perinatal stroke. Associations with motor outcome in arterial but not venous strokes suggest differing glial responses may play a role in tissue remodeling and developmental plasticity following early focal brain injury.
Anti-inflammatory Activity of the Protein Z-Dependent Protease Inhibitor
Authors: Razanakolona Mahita , Adam Frédéric , Bianchini Elsa , Saller François , Carvalho Allan de , Diehl Jean-Luc , Denis Cécile V. , Meziani Ferhat , Borgel Delphine , Helms Julie , Vasse Marc
Published: June 2021

The protein Z (PZ)-dependent plasma protease inhibitor (ZPI) is a glycoprotein that inhibits factor XIa and, in the presence of PZ, FXa. Recently, ZPI has been shown to be an acute-phase protein (APP). As usually APPs downregulate the harmful effects of inflammation, we tested whether ZPI could modulate the increase of cytokines observed in inflammatory states. We observed that recombinant human ZPI (rhZPI) significantly decreases the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor- α (TNF-α) induced by lipopolysaccharide (LPS) in a whole blood model. This inhibitory effect was unaffected by the presence of PZ or heparin. A ZPI mutant within the reactive loop center ZPI (Y387A), lacking anticoagulant activity, still had an anti-inflammatory activity. Surprisingly, rhZPI did not inhibit the synthesis of IL-6 or TNF-α when purified monocytes were stimulated by LPS, whereas the inhibitory effect was evidenced when lymphocytes were added to monocytes. The requirement of lymphocytes could be due to the synthesis of CCL5 (RANTES), a chemokine mainly produced by activated lymphocytes which is induced by rhZPI, and which can reduce the production of proinflammatory cytokines in whole blood. Lastly, we observed that the intraperitoneal injection of rhZPI significantly decreased LPS-induced IL-6 and TNF-α production in mouse plasma.
The Pattern of Anosmia in Non-hospitalized Patients in the COVID-19 Pandemic: A Cross-sectional Study
Authors: Elsherief Hossam , Amer Mohmed , Abdel-Hamid Ahmed S. , El-Deeb Mohamed E. , Negm Ahmed , Elzayat Saad
Published: June 2021

Introduction It is now evident that the loss of smell and/or taste may be consistent accompanying symptoms of the SARS-CoV-2 infection.

Objective To estimate the social behavior of recent anosmic non-hospitalized patients in the COVID-19 pandemic and to try to obtain the natural pattern in society in a cross-sectional study.

Methods A cross-sectional study conducted on 4,860 patients with anosmia complaints during the COVID-19 pandemic. Patients who needed a consultation for an anosmia complaint confirmed that they had completed the survey regarding age, gender, history of general diseases, history of nasal disease, associated COVID-19 symptoms, smoking, blood group, and risk factors.

Results A total of 4,860 patients with a mean age of 34.26 ± 11.91 years completed the study. There was a predominance of female patients: 3,150 (58.9%). Most patients (4,083 patients; 83%) developed sudden anosmia. In 85% (4131 patients) of the patients, a previous history of contact with anosmic patients was present. The most prevalent blood group was O (39%). In total, 67.4% of the patients underwent medical treatment. A history of unusual influenza attacks in December 2020 was reported by by 27% (1312 patients) of the patients.

Conclusion Despite large diversity of behaviors among anosmic patients in the COVID-19 pandemic, we can observe a great similarity in the pattern of anosmia in non-hospitalized patients, especially in the way it spreads, the predisposing factors, and the individual recovery.
Effect of Retinal Injury Induced by Laser Photocoagulation on Visuospatial Memory in Mouse Model
Authors: Mehra Priya , Bali Parul , Singh Jagtar , Saha Pradip Kumar , Anand Akshay
Published: June 2021

Visual pathway reveals the connection between neuronal activity of the brain and eye. The neural networks of brain amplify the retinal signals resulting in the formation of visual image. The laser injury in the retina may affect the visual pathway and may lead to disruption of neuronal signals/activity. Therefore, we aimed to study the effect of retinal injury induced by laser on cognitive abilities in laser-induced mouse model. We have established laser model to understand the relation between retina and brain by disrupting retinal pigment epithelial (RPE) layer and evaluate the effect of laser-induced retinal injury on visuospatial memory. Age- and sex-matched C57BL/6J male mice were taken for conducting the experiments. The laser model was established by using laser photocoagulator to disrupt the RPE layer of the retina. After defined irradiation of laser onto mouse retina, the fundus fluorescein angiography was performed to confirm the laser spots. The visuospatial and short-term memory was performed using neurobehavioral test, that is, Morris water maze (MWM), and passive avoidance, respectively. In MWM experiment, results showed that escape latency time, which was taken by healthy and laser-injured mice was comparable. This was further validated by another neurobehavioral analysis, that is, passive avoidance that showed nonsignificant difference between these two groups using independent t-test. Visuospatial memory may not be affected by retinal injury induced by laser photocoagulation. It may depend on the power of the laser and duration of the laser. The severe injury in the retina such as optic nerve damage may cause dysfunctioning of visual pathway.
Analysis of MYO1H Gene Polymorphism in Skeletal Class-III Malocclusion Due to Mandibular Prognathism
Authors: Atteeri Anjana , Neela Praveen Kumar , Mamillapalli Pavan Kumar , Sesham Vasu M. , Keesara Sreekanth , Chandra Jaya , Monica Udayini , Mohan Vasavi , Miryala Shubhangi , Khan Fatema A. , Makthal Priyanka
Published: June 2021

Background Mandibular prognathism (MP) is a craniofacial deformity resulting from the combined effects of environmental and genetic factors. Although various linkage and genome-wide association studies for mandibular prognathism have identified multiple strongly associated regions and genes, the causal genes and variants responsible for the deformity remained ambiguous.

Aim This research work was aimed to study the association between polymorphism rs10850110 of the MYO1H gene and skeletal class-III malocclusion in our local population.

Materials and Methods Thirty patients with skeletal class III due to mandibular prognathism in the study group and 30 patients with skeletal class I in the control group were selected for this study. These patients were from both sexes and above age 10 years. Based on the cephalometric values, patients were categorized into study and control groups. SNB (angle between sella, nasion and point B at nasion) greater than 82 degrees with an ANB (angle between point A, nasion and point B at nasion) of less than 0 degrees in the study group and ANB (angle between point A, nasion and point B at nasion) of 2 to 4 degrees in the control group were categorized. The polymorphism (rs10850110) of the MYO1H gene was genotyped using polymerase chain reaction and restriction fragment length polymorphism. Associations were tested with SNP exact test using SNPstats software.

Results The single-nucleotide polymorphism rs10850110 showed a statistically significant association with mandibular prognathism. The G allele of marker rs10850110 (5′ of myosin1H - MYO1H) was overrepresented when compared with the “A” allele in mandibular prognathism cases (p < 0.0001), and this was very significant.

Conclusion These results suggest that the rs10850110 polymorphism of the MYO1H gene is associated with an increased risk for mandibular prognathism.
Distress and the Long-Stay Pediatric Intensive Care Unit Admission: A Longitudinal Study of Parents and the Medical Team
Authors: Salant Jennifer A. , Gangopadhyay Maalobeeka , Jia Haomiao , Wocial Lucia D. , Edwards Jeffrey D.
Published: June 2021

Prolonged critical illness in children has emotional consequences for both parents and providers. In this observational cohort study, we longitudinally surveyed anxiety and depression in parents and moral distress in pediatric intensive care unit (PICU) providers (attendings, fellows, and bedside registered nurses) and explored their trajectories and relationships. Anxiety/depression and provider moral distress were measured using the Hospital Anxiety and Depression Scale and the Moral Distress Thermometer, respectively. The relationships of parental and provider distress were evaluated using Spearman's correlations, and their trajectories and potentially associated variables were explored using quadratic random slope and intercept models. Predetermined associated factors included demographic and clinical factors, including parent psychosocial risk and intubation status. We found parental anxiety and depression decreased over their child's admission, and parental psychosocial risk was significantly associated with anxiety (coefficient = 4.43, p < 0.001). Clinicians in different roles had different mean levels and trajectories of moral distress, with fellows reporting greater distress early in admissions and nurses later in admissions. Parental anxiety/depression and provider distress were significantly, though moderately, correlated. We conclude that anxiety and depression in parents of children with prolonged PICU admissions and the moral distress of their clinicians correlate and vary over time and by provider role.
40.1.8 Product Subclass 8: Piperazines
Authors: Ye Z.-S.
Published: June 2021

The piperazine unit is widely distributed in natural products and life-saving small-molecule pharmaceuticals. It is the third most common nitrogen heterocycle occurring in pharmaceuticals approved by the U. S. Food and Drug Administration. This chapter covers strategies for the synthesis and transformations of piperazines, with both classical methods and recent developments reviewed. A major focus is on cyclization reactions such as intramolecular hydroaminations, multicomponent approaches, and routes from ethane-1,2-diamine substrates. Also discussed are approaches based on hydrogenation of (hydro)pyrazines by heterogeneous catalysis and by (asymmetric) homogeneous catalysis. Finally, a variety of transformations involving modification of a substituent on a piperazine ring are surveyed, including arylations, alkylations, and oxidations.
48.3.3 Cyclobutanes (Update 2021)
Authors: Xiong Y. , Guo R. , Zhang G. Z.
Published: June 2021

This chapter is an update to the earlier Science of Synthesis contribution (Section 48.3), and describes methods for the formation of cyclobutanes reported in the period 2009–2019. The focus is on recent advances in the synthetic preparations and applications of cyclobutanes via transition-metal-catalyzed and photochemical processes.
Defect characterization and charge transport measurements in high-resolution Ni/n-4H-SiC Schottky barrier radiation detectors fabricated on 250 μm epitaxial layers
Authors: Kleppinger Joshua W. , Chaudhuri Sandeep K. , Karadavut OmerFaruk , Mandal Krishna C.
Published: June 2021

Advances in the growth processes of 4H-SiC epitaxial layers have led to the continued expansion of epilayer thickness, allowing for the detection of more penetrative radioactive particles. We report the fabrication and characterization of high-resolution Schottky barrier radiation detectors on 250 μm thick n-type 4H-SiC epitaxial layers, the highest reported thickness to date. Several 8 × 8 mm2 detectors were fabricated from a diced 100 mm diameter 4H-SiC epitaxial wafer grown on a conductive 4H-SiC substrate with a mean micropipe density of 0.11 cm−2. From the Mott–Schottky plots, the effective doping concentration was found to be in the range (0.95–1.85) × 1014 cm−3, implying that full depletion could be achieved at ∼5.7 kV (0.5 MV/cm at the interface). The current-voltage characteristics demonstrated consistently low leakage current densities of 1–3 nA/cm2 at a reverse bias of −800 V. This resulted in the pulse-height spectra generated using a 241Am alpha source (5486 keV) manifesting an energy resolution of less than 0.5% full width at half maximum (FWHM) for all the detectors at −200 V. The charge collection efficiencies (CCEs) were measured to be 98–99% with no discernable correlation to the energy resolution. A drift-diffusion model fit to the variation of CCE as a function of bias voltage, revealed a minority carrier diffusion length of ∼10 μm. Deep level transient spectroscopy measurements on the best resolution detector revealed that the excellent performance was the result of having ultralow concentrations of the order of 1011 cm−3 lifetime limiting defects—Z1/2 and EH6/7.
Understanding supercooling mechanism in sodium sulfate decahydrate phase-change material
Authors: Goswami Monojoy , Kumar Navin , Li Yuzhan , Hirschey Jason , LaClair Tim J. , Akamo Damilola O. , Sultan Sara , Rios Orlando , Gluesenkamp Kyle R. , Graham Samuel
Published: June 2021

Salt hydrate-based phase-change materials are considered promising for future heat storage applications in residential heating/cooling systems. Smooth phase transition from the liquid to solid phase and vice versa is essential for effective heat exchanger; however, supercooling in salt hydrates delays the onset of liquid–solid phase transition. We investigate the molecular level mechanism of supercooling in sodium sulfate decahydrate (SSD). SSD is a complex salt hydrate whose properties are governed by electrostatic forces that include pure Coulombic interactions as well as hydrogen bonds. Experimentally, we examine the importance of a nucleator in reducing supercooling temperatures. We investigated the effect of various mass concentrations of a borax nucleator on a decrease of supercooling temperatures. Molecular dynamics simulation techniques are used to obtain a basic understanding of supercooling in SSD. We observe that by introducing borax as a nucleator, there is a decrease in the supercooling temperature before nucleation. Our molecular dynamics simulations show that long-range electrostatics between sodium and sulfate ion pairs and that with polar water molecules is responsible for delayed nucleation in SSD that results in supercooling, and also, dynamics of charged molecules slows down. The lack of crystallization leads to amorphous structures in supercooled SSD.
Machine learned Hückel theory: Interfacing physics and deep neural networks
Authors: Zubatiuk Tetiana , Nebgen Benjamin , Lubbers Nicholas , Smith Justin S. , Zubatyuk Roman , Zhou Guoqing , Koh Christopher , Barros Kipton , Isayev Olexandr , Tretiak Sergei
Published: June 2021

The Hückel Hamiltonian is an incredibly simple tight-binding model known for its ability to capture qualitative physics phenomena arising from electron interactions in molecules and materials. Part of its simplicity arises from using only two types of empirically fit physics-motivated parameters: the first describes the orbital energies on each atom and the second describes electronic interactions and bonding between atoms. By replacing these empirical parameters with machine-learned dynamic values, we vastly increase the accuracy of the extended Hückel model. The dynamic values are generated with a deep neural network, which is trained to reproduce orbital energies and densities derived from density functional theory. The resulting model retains interpretability, while the deep neural network parameterization is smooth and accurate and reproduces insightful features of the original empirical parameterization. Overall, this work shows the promise of utilizing machine learning to formulate simple, accurate, and dynamically parameterized physics models.
Exploring the influence of experimental parameters on the interaction of asymmetric ω/2ω fields with water isotopologues
Authors: Kechaoglou Emmanouil , Ferentinou Katerina , Kaziannis Spyridon , Kosmidis Constantine
Published: June 2021

Water isotopologues are doubly ionized by phase-controlled asymmetric ω/2ω laser fields, and their two-body fragmentation channels leading to pairs of OH+/H+ [channel (I)] and H2+/O+ [channel (II)] are systematically investigated. The dependence of the ionic fragments on phase distinguishes between two dissociation channels, while a quantity that is proportional to the directionality of the ejected fragments, called asymmetry parameter (β), is measured as a function of composite field’s phase. The dependence of the two channels’ asymmetry amplitude (β0) on the experimental parameters that characterize the composite field (wavelength, anisotropic shape, and total intensity) is found to differ significantly. The channel leading to H2+ and O+ ions’ ejection shows increased asymmetry compared to the other channel and is found to be dependent on excitation of overtones and combinations of vibrational modes as well as from the field’s shape and intensity. The asymmetry (β) of the channel leading to the release of a H+ and an OH+ ions is far less sensitive to the experimental parameters. Inspection of the individual OH+ peak’s dependence on phase reveals information on the effect of the field’s profile, which is unclear when asymmetry (β) is inspected.
Photoelectrical detection of nitrogen-vacancy centers by utilizing diamond lateral p–i–n diodes
Authors: Murooka T. , Shiigai M. , Hironaka Y. , Tsuji T. , Yang B. , Hoang T. M. , Suda K. , Mizuno K. , Kato H. , Makino T. , Ogura M. , Yamasaki S. , Hatano M. , Iwasaki T.
Published: June 2021

We demonstrate a photoelectrical readout of negatively charged nitrogen-vacancy (NV−) centers by utilizing a lateral diamond p–i–n diode structure. We found that the photocarriers generated at NV centers are efficiently extracted in the depletion layer even at zero voltage. The transport mechanism for photoexcited minority carriers was investigated by varying the nitrogen ion implantation dose. The minority carrier diffusion length decreased when the photocarriers passed through the implantation region, particularly at a high nitrogen ion dose. From photoelectrically detected magnetic resonance (PDMR) measurements, the photocurrent was found to exhibit a minimum at approximately 2.87 GHz upon microwave irradiation with a contrast of 12%, while this dip was observed to split upon the application of a static magnetic field. The PDMR signal was found to depend on the measurement position. This study paves the way for efficient electrical detection for quantum sensors based on device technologies.
APPsα rescues impaired Ca2+homeostasis in APP- and APLP2-deficient hippocampal neurons
Authors: Ludewig Susann , Herrmann Ulrike , Michaelsen-Preusse Kristin , Metzdorf Kristin , Just Jennifer , Bold Charlotte , Müller Ulrike C. , Korte Martin
Published: June 2021

Significance

Ca2+dysfunction is correlated to the progression of Alzheimer’s disease; mechanistic insight into the physiological role of the amyloid precursor protein (APP) for Ca2+homeostasis is still missing. We demonstrate that loss of APP and its homolog APLP2, but not APLP2 alone, impairs Ca2+handling and synaptic plasticity because of altered function of endoplasmic reticulum Ca2+stores caused by altered expression and function of the SERCA-ATPase as well as by expression of store-operated Ca2+channel–associated proteins Stim1 and Stim2. Long-term expression of the APPsα ectodomain restored physiological Ca2+homeostasis, protein expression, and synaptic plasticity in APP/APLP2 cDKO cultures, emphasizing the role of the APP family and especially of the ectodomain APPsα in Ca2+homeostasis, thereby highlighting its therapeutic potential.
The landscape of innovation in bacteria, battleships, and beyond
Authors: Burnham Terence C. , Travisano Michael
Published: June 2021

We draw lessons from microbial experimental evolution and naval warfare to improve the understanding of innovation in financial markets. Major financial innovations often arise without explicit societal planning because novel approaches can be favored by markets, in a manner strikingly parallel to natural selection. We utilize the concept of an adaptive landscape to characterize environments that increase the speed and magnitude of innovation. We apply this adaptive landscape framework to innovation in portfolio management. We create a general taxonomy for understanding and nurturing innovation.
Evolved attitudes to risk and the demand for equity
Authors: Robson Arthur J. , Orr H. Allen
Published: June 2021

Significance

An important puzzle in economics concerns the equity premium. Why does anyone hold bonds given the option of holding stocks? Stocks are riskier, but they do much better on average in the long run than bonds, thus generating the equity premium puzzle. Standard economic models of preferences have difficulty accounting for this anomaly on the basis of a level of risk aversion that is consistent with risk-taking behavior elsewhere. We show that considering the biological basis of preferences is fruitful here. Biological evolution predicts that individuals should be more averse to aggregate—shared—risks than they are to risks that are idiosyncratic—personal. Since the stock market involves aggregate risk, this helps to resolve the puzzle.
Moonshots, investment booms, and selection bias in the transmission of cultural traits
Authors: Hirshleifer David , Plotkin Joshua B.
Published: June 2021

Significance

What drives innovation, risk taking, and investment booms? We study these phenomena using a model of decision making by firms that make biased observations of prior returns. We assume that firms are more likely to observe large successes than small successes or failures. As a result, firms tend to become overly optimistic, leading to irrational booms in investment. Booms may eventually collapse, or they may last forever. We describe the cultural evolutionary sources of these effects. Evolution of investment behavior is driven not only by copying successful strategies, but also by cognitive reasoning about which behaviors are more likely to succeed. This account provides an explanation for investment booms, merger and IPO waves, and waves of technological innovation.
Stat3
loss in mesenchymal progenitors causes Job syndrome–like skeletal defects by reducing Wnt/β-catenin signaling
Authors: Yadav Prem Swaroop , Feng Shuhao , Cong Qian , Kim Hanjun , Liu Yuchen , Yang Yingzi
Published: June 2021

Significance

Understanding the cell origin and molecular mechanisms underlying rare genetic diseases provides invaluable insights into human biology and pathology of not only rare genetic diseases but also related common disorders. Autosomal dominant hyper immunoglobulin-E syndrome (AD-HIES) or Job syndrome is a genetic disease with skeletal defects resulting from mutations in the STAT3 gene. We have modeled the skeletal abnormality in Job Syndrome by deleting Stat3 using cell-specific Cre lines. We found that Stat3 is required in osteoblast lineage cells for skeletal development by maintaining Wnt/β-catenin signaling. Deletion of
Stat3
resulted in impaired osteoblast differentiation due to reduced Wnt/β-catenin signaling with upregulated
Sost
expression. Our work provides a foundation for further understanding the principles whereby
Stat3
governs bone formation and maintenance.
Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic
Authors: Etxeberria Iñaki , Bolaños Elixabet , Teijeira Alvaro , Garasa Saray , Yanguas Alba , Azpilikueta Arantza , Kavanaugh William M. , Vasiljeva Olga , Belvin Marcia , Howng Bruce , Irving Bryan , Tipton Kimberly , West James , Mei Li , Korman Alan J. , Sega Emanuela , Olivera Irene , Cirella Assunta , Ochoa Maria C. , Rodriguez Maria E. , Melero Ana , Sanmamed Miguel F. , Engelhardt John J. , Melero Ignacio
Published: June 2021

Significance

CD137 (4-1BB) is a target for tumor immunotherapy, which has been pursued in clinical trials with agonist antibodies or the natural ligand (CD137L). Liver toxicity is a serious dose-limiting problem that may be circumvented by selective functional or physical targeting to the tumor microenvironment. A CD137 agonist antibody prodrug that is preferentially activated by tumor-associated proteases constitutes an appealing way to enhance safety while preserving efficacy.
Critical Assessment 40: A search for the eutectic system of high-temperature cast aluminium alloys
Authors: Czerwinski Frank
Published: June 2021

A quest for the eutectic system of novel cast aluminium alloys, having high-temperature capabilities, is critically assessed with two potential candidates of Al–Al3Ni and Al–Al11Ce3 examined and compared to the presently used Al–Si base. The conventionally cast Al–Al3Ni and Al–Al11Ce3 eutectics do not exhibit the anticipated advantage over Al–Si in strengthening retention at temperatures up to 500°C. The promising differences between diffusivities of silicon, nickel, and especially cerium in aluminium, and eutectic melting temperatures, accompanied by high coarsening resistance of Al3Ni, Al11Ce3 phases and the eutectic hardness retention are inconsistent with observed similarities in the temperature-related strengthening-reduction of all three eutectics. These findings will help defining the criteria for development of the eutectic system, suitable for future heat-resistant aluminium alloys.
Further progress in understanding of myofibrillar function in health and disease
Authors: Cremo Christine , Moss Richard L. , Granzier Henk
Published: June 2021

The July 2021 issue of JGP is a collection of peer-reviewed articles focused on the function and dynamic regulation of contractile systems in muscle and non-muscle cells.
Finite-time singularity formation for an active scalar equation
Authors: Elgindi Tarek , Ibrahim Slim , Shen Shengyi
Published: June 2021

We introduce an active scalar equation with a similar structure to the 3D Euler equations. Through studying the behavior of scale-invariant solutions, we show that compactly supported Lipschitz solutions belonging to

C

∞

(

R

2

\

{

0

}

)

can become singular in finite time. The interesting feature here is that we can achieve this in the absence of spatial boundaries.
On the structure in the ΛN cross section at the ΣN threshold *
Authors: Haidenbauer Johann , Meißner Ulf-G.
Published: June 2021

The complexity of threshold phenomena is exemplified on a prominent and long-known case - the structure in the

cross section (invariant mass spectrum) at the opening of the

channel. The mass splitting between the

baryons together with the angular momentum coupling in the

-

partial wave imply that, in principle, up to six channels are involved. Utilizing hyperon-nucleon potentials that provide an excellent description of the available low-energy

and

scattering data, the shape of the resulting

cross section is discussed and the poles near the

threshold are determined. Evidence for a strangeness

dibaryon is provided, in the form of a (unstable)

bound state in the vicinity of the

threshold. Predictions for level shifts and widths of

atomic states are given.
Advanced high dynamic range fluorescence microscopy with Poisson noise modeling and integrated edge-preserving denoising
Authors: Brinkmann Eva-Maria , Brinker Klaus , Rüberg Silvia , Müller Werner
Published: June 2021

In the last decades, fluorescence microscopy has evolved into a powerful tool for modern cell biology and immunology. However, while modern fluorescence microscopes allow to study processes at subcellular level, the informative content of the recorded images is frequently constrained by the limited dynamic range of the camera mounted to the optical system. In addition, the quality of acquired images is generally affected by the typically low-light conditions that lead to comparatively high levels of noise in the data. Addressing these issues, we introduce a variational method for high dynamic range (HDR) imaging in the context of fluorescence microscopy that explicitly accounts for the Poisson statistics of the unavoidable signal-dependent photon shot noise and complements HDR image reconstruction with edge-preserving denoising. Since the proposed model contains a weight function to confine the influence of under- and overexposed pixels on the result, we briefly discuss the choice of this function. We evaluate our approach by showing HDR results for real fluorescence microscopy exposure sequences acquired with the recently developed MACSimaTM System for fully automated cyclic immunofluorescence imaging. These results are obtained using a first-order primal-dual implementation. On top of this, we also provide the corresponding saddle-point and dual formulations of the problem.
Irreducible tensor products of representations of covering groups of symmetric and alternating groups
Authors: Morotti Lucia
Published: June 2021

In this paper we completely classify irreducible tensor products of covering groups of symmetric and alternating groups in characteristic≠2\not =2.
Subareolar Tissue Biopsy Predicts Occult Nipple Involvement in Nipple-Sparing Mastectomies
Authors: Ma Lucy X , Michaels Aya Y , Ginter Paula S
Published: June 2021

Objectives

Subareolar tissue is examined during nipple-sparing mastectomy (NSM) to minimize the risk of occult malignancy within the preserved nipple. A positive subareolar tissue biopsy typically warrants subsequent nipple excision. We study the factors associated with a positive subareolar tissue biopsy, the rate of residual malignancy in subsequent nipple excisions, and the value of subareolar tissue biopsy intraoperative frozen section (IOF).

Methods

We identified 1,026 consecutive NSMs with separately submitted subareolar tissue biopsies over a 5.5-year period. Clinicopathologic data were reviewed. We examined concordance rates between subareolar tissue biopsy and subsequent nipple excisions as well as IOF diagnosis and permanent control diagnosis.

Results

Among cases of therapeutic NSM, the rate of a positive subareolar tissue biopsy was 7.2%. Multifocal/multicentric disease (P = .0005), presence of lymphovascular invasion (P = .033), and nodal involvement (P = .006) were significantly associated with a positive subareolar tissue biopsy. Thirty-nine of 41 cases with positive subareolar biopsies underwent subsequent nipple excision, with 20 (51%) showing residual carcinoma. Among all IOF samples, 9 (3.3%) showed a discrepancy between the IOF and permanent diagnoses, mostly because of false-negatives.

Conclusions

A positive subareolar tissue biopsy predicts residual carcinoma in the excised nipples in 51% of cases. IOF is accurate and reliable.
Linguistic positivity bias in academic writing: A large-scale diachronic study in life sciences across 50 years
Authors: Wen Ju , Lei Lei
Published: June 2021

Recent studies found linguistic positivity bias in academic writing, that is, researchers tend to present their works with more positive words than negative ones. The present study aims to examine the issue from a diachronic perspective, and it is probably the first one that employed a mixed method of both a small lexicon analysis and sentiment analysis in this line of research. Specifically, a series of experiments were performed based on a corpus of 775,460 abstracts published between 1969 and 2019 in 123 scientific journals covering 12 research disciplines in life sciences. The results demonstrated a linguistic positivity bias in academic writing. More importantly, a significant upward trend of linguistic positivity bias was observed over the past 5 decades. Major communicative functions of positive and negative sentences are also analysed. Reasons for this linguistic positivity bias are explored from the perspectives of publication pressure/bias, employment of linguistic devices to promote research, and language use for political correctness purposes. Lastly, implications for authors and learners of academic writing and for researchers of sentiment analysis are also discussed.
NADPH is important for isobutanol tolerance in a minimal medium of Saccharomyces cerevisiae
Authors: Yoshikawa Yuki , Nasuno Ryo , Takagi Hiroshi
Published: June 2021

We showed that the isobutanol sensitivity in glucose-6-phosphate dehydrogenase-deficient cells of the yeast Saccharomyces cerevisiae was rescued by an alternative NADPH producer, acetaldehyde dehydrogenase, but not in the cells lacking 6-phosphogluconate dehydrogenase. This phenotype correlated with the intracellular NADPH/NADP+ ratio in yeast strains. Our findings indicate the importance of NADPH for the isobutanol tolerance of yeast cells.
Lipidomic traits of plasma and cerebrospinal fluid in amyotrophic lateral sclerosis correlate with disease progression
Authors: Sol Joaquim , Jové Mariona , Povedano Monica , Sproviero William , Domínguez Raul , Piñol-Ripoll Gerard , Romero-Guevara Ricardo , Hye Abdul , Al-Chalabi Ammar , Torres Pascual , Andres-Benito Pol , Area-Gómez Estela , Pamplona Reinald , Ferrer Isidro , Ayala Victòria , Portero-Otín Manuel
Published: June 2021

Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain—an index of neuronal damage—were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P < 0.05; n = 27 for P < 0.01) than CSF (n = 17 for raw P < 0.05; n = 4 for P < 0.01), with almost no overlapping differential species, mainly characterized by an increased content of triacylglyceride species in plasma and decreased in CSF. Of note, false discovery rate correction indicated that one of the CSF lipids (monoacylglycerol 18:0) had high statistic robustness (false discovery rate-P < 0.01). Plasma lipidomes also varied significantly with the main involvement at onset (bulbar, spinal or respiratory). Notably, faster progression cases showed particular lipidome fingerprints, featured by decreased triacylclycerides and specific phospholipids in plasma, with 11 lipids with false discovery rate-P < 0.1 (n = 56 lipids in plasma for raw P < 0.01). Lipid species associated with progression rate clustered in a relatively low number of metabolic pathways, mainly triacylglyceride metabolism and glycerophospholipid and sphingolipid biosynthesis. A specific triacylglyceride (68:12), correlated with neurofilament content (r = 0.8, P < 0.008). Thus, the present findings suggest that systemic hypermetabolism—potentially sustained by increased triacylglyceride content—and CNS alterations of specific lipid pathways could be associated as modifiers of disease progression. Furthermore, these results confirm biochemical lipid heterogeneity in amyotrophic lateral sclerosis with different presentations and progression, suggesting the use of specific lipid species as potential disease classifiers.
Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Roman Yuani M , Burela Paula Alejandra , Pasupuleti Vinay , Piscoya Alejandro , Vidal Jose E , Hernandez Adrian V
Published: June 2021

Background

We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19).

Methods

Published and preprint randomized controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods.

Results

Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12–1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, −.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM.

Conclusions

Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.