bluuebunny/crossref_metadata_2025 huggingface dataset:
(Don’t) bite the hand that feeds you: do critical interest organizations gain less funding in the EU?
Authors: Crepaz Michele , Hanegraaff Marcel
Published: April 2022

In this study we test whether interest organizations that are confrontational towards EU institutions are less successful than their more cooperative counterparts in obtaining funding from the European Commission (EC). The transfer of public funds to interest organizations is a key dynamic in state-civil society relationships. Research shows that organizations, especially public groups, often heavily rely on public funds to the point that, without funds, many would cease to exist. ‘Don’t bite the hand that feeds you’ is thus a popular expression among leaders of organizations who apply for funds. Scholars document a widespread perception among group leaders that a confrontational attitude towards the state can lead to curtail of public funds. This perception is based on the assumption that state institutions use public funding to discipline confrontational interest organizations. We test this assumption using quantitative and qualitative data collected from a survey of 270 interest organizations who applied for EC funding between 2015 and 2018. Our findings suggest that, while almost half of our survey respondents feel that critical attitudes towards the EU would have negative consequences for their funding applications, empirically, confrontational and cooperative organizations have the same chances of obtaining EC grants. This finding is robust across different interest organization categories, including when non-applicants and mortality anxiety are considered in the analysis. The results add a new layer to resource dependency theory pointing at the incongruence between an organization’s perception of its relationship with public institutions and the observation of that relationship.
Vorteile durch aktives Lernen bei Schülerinnen und Schülern
Authors: Opitz Ben , Ruggeri Azzurra
Published: April 2022

Zusammenfassung. Einleitung: Das Konzept des aktiven Lernens gewinnt zunehmend an Bedeutung und ist mit entsprechenden Lerntheorien sowie Unterrichtstechniken einhergegangen. Der Begriff des aktiven Lernens umfasst eine große Bandbreite an Konzepten, wodurch ein Verständnis einzelner, dem aktiven Lernen zugrundeliegender kognitiver Prozesse erschwert wird. Kognitionspsychologische Untersuchungsergebnisse ermöglichen ein präziseres Verständnis aktiver Lernprozesse und liefern somit wertvolle Impulse für eine evidenzbasierte Unterrichtspraxis. Methode: In der vorliegenden Übersichtsarbeit werden Vorteile des aktiven Lernens anhand ausgewählter kognitionspsychologischer Forschungsergebnisse aufgezeigt sowie Implikationen für die Bildungspraxis diskutiert. Dafür werden zugrundeliegende Mechanismen aktiven Lernens beleuchtet. Im Anschluss wird dargelegt, wann erste vorteilhafte Effekte in der Entwicklung auftreten und weshalb positive Effekte auch für Kinder mit einer diagnostizierten Autismus-Spektrum-Störung gelten. Ergebnisse und Diskussion: Die Forschungsergebnisse zeigen zusammengenommen, dass Kinder entgegen früheren Annahmen schon ab einem Alter von 6 bis 8 Jahren von aktiven Lernstrategien hinsichtlich einer gesteigerten Gedächtnisleistung profitieren und dass sie dies durch effektive Anpassungen ihrer gewählten Lernstrategien tun. Abschließend werden Implikationen für die Bildungspraxis diskutiert.
CAN Stop
Authors: Thomasius Rainer , Baldus Christiane , Moré Kerstin , Miranda Eggers Alejandra , Weymann Nina , Reis Olaf
Published: April 2022

Das manualisierte Gruppenprogramm CAN Stop richtet sich an junge Menschen, die einen problematischen Cannabiskonsum aufweisen. Ziel ist es, Teilnehmende dabei zu motivieren, ihren Konsum zu überdenken und zu reduzieren oder dauerhaft zu beenden. Das Programm besteht aus acht 90-minütigen Sitzungen und basiert auf den Prinzipien der Verhaltenstherapie und des Motivational Interviewings. An dem stark strukturierten Programm nehmen durchschnittlich acht Teilnehmende im Alter von 14 bis 21 Jahren teil. Das Programm ist in verschiedensten Settings anwendbar und wurde erfolgreich in der ambulanten Jugend- und Suchthilfe, im medizinischen Versorgungsbereich und in Jugendhaftanstalten durchgeführt.
Das Manual liegt in je einer Variante für stationäre und für ambulante Gruppen vor und enthält einen umfangreichen Anhang mit Arbeitsmaterialien. Diese können nach erfolgter Registrierung von der Website des Hogrefe Verlags heruntergeladen werden.
Ressourcenorientierte Gruppentherapie bei chronischer Depression
Authors: Trösken Anne , Renneberg Babette
Published: April 2022

Verhaltenstherapeutische Gruppentherapie bietet eine sehr gute Ergänzung und Intensivierung der ambulanten Einzeltherapie. Insbesondere Menschen mit chronischen Depressionen profitieren von solchen multimodalen und -professionellen Behandlungsstrategien. Für diese Patientinnen und Patienten wurde das in diesem Manual vorgestellte strukturierte gruppentherapeutische Vorgehen entwickelt. Es ergänzt bewährte kognitiv-verhaltenstherapeutische Techniken durch aktive und sinnesbezogene Übungen und ermöglicht so intensive Lernerfahrungen im Gruppenkontext. Dabei stehen Ressourcenaufbau und Veränderungswissen im Vordergrund.
Die theoretischen Grundlagen und empirischen Befunde zur Entstehung und Aufrechterhaltung des Störungsbildes sowie zu geeigneten Behandlungsstrategien werden zunächst umfassend dargestellt und zeigen Perspektiven zum Verständnis und zur Veränderung chronisch depressiven Erlebens auf. Der zweite Teil des Manuals beschreibt ausführlich und anhand von vielen Beispielen die Durchführung der 12 Sitzungen umfassenden Gruppentherapie. Die im Buch erwähnten, illustrierten Informations- und Arbeitsblätter können nach erfolgter Registrierung von der Hogrefe Website heruntergeladen werden.
Ratgeber Kaufsucht
Authors: Müller Astrid , Laskowski Nora M.
Published: April 2022

Kaufsucht betrifft relativ viele Menschen, wird aber häufig verheimlicht, bagatellisiert und übersehen. Dabei hat die Störung viele negative Konsequenzen für die betroffenen Personen und ihre Angehörigen und ist mit einem enormen Leidensdruck verbunden. Dieser Ratgeber wendet sich an Menschen, die selbst an einer Kaufsucht und deren Folgen leiden, sowie an deren Angehörige und weitere Personen aus dem sozialen und Arbeitsumfeld. Der Ratgeber will dazu beitragen, die Störung besser zu verstehen, und liefert dazu Informationen über den Verlauf, die Ursachen, die Folgen und Behandlungsmöglichkeiten.
Der Ratgeber beschreibt zunächst, wie sich eine Kaufsucht äußert, wie man sie erkennen kann und welche Konsequenzen für die Betroffenen damit verbunden sind. Zudem wird kurz auf die Häufigkeit von Kaufsucht in der Bevölkerung sowie auf den Zusammenhang von Kaufsucht mit anderen psychischen Störungen eingegangen. Anschließend stehen die Faktoren, die zur Entstehung einer Kaufsucht führen können, im Vordergrund. Ein weiteres Kapitel informiert Betroffene über Selbsthilfemöglichkeiten und skizziert die wesentlichen Inhalte einer Therapie. Schließlich erhalten Angehörige Empfehlungen, wie sie Betroffene unterstützen können.
Ratgeber Alkoholabhängigkeit
Authors: Lindenmeyer Johannes
Published: April 2022

Die meisten Menschen sind schockiert, wenn ihnen gegenüber der Verdacht geäußert wird, sie könnten ein Alkoholproblem haben. Der Ratgeber soll dabei helfen, dass sich Betroffene selbst ein qualifiziertes Urteil über ihre eigene Situation bilden, die verschiedenen Formen und die Entstehung der Alkoholabhängigkeit besser verstehen sowie einen gangbaren Ausweg aus ihrer Situation finden können.
Die Neuauflage des Ratgebers erläutert, woran man eine Alkoholabhängigkeit erkennt und wie sie entsteht. Der Ratgeber beschreibt die Suchtbehandlung und gibt Betroffenen Anregungen dazu, was sie selbst gegen ihr Trinken unternehmen können. Zudem will der Ratgeber Angehörige in ihrer Sicht bestärken, dass etwas unternommen werden soll, aber auch Verständnis dafür wecken, wie schwer es für Betroffene ist, sich das wahre Ausmaß ihres Alkoholproblems einzugestehen. Beides – Verständnis und Festigkeit von Angehörigen – kann die Behandlung von Betroffenen entscheidend unterstützen.
Differences in Tropical Rainfall in Aquaplanet Simulations With Resolved or Parameterized Deep Convection
Authors: Rios‐Berrios Rosimar , Bryan George H. , Medeiros Brian , Judt Falko , Wang Wei
Published: April 2022

This study investigates the effects of resolved deep convection on tropical rainfall and its multi‐scale variability. A series of aquaplanet simulations are analyzed using the Model for Prediction Across Scales‐Atmosphere with horizontal cell spacings from 120 to 3 km. The 3‐km experiment uses a novel configuration with 3‐km cell spacing between 20°S and 20°N and 15‐km cell spacing poleward of 30°N/S. A comparison of those experiments shows that resolved deep convection yields a narrower, stronger, and more equatorward intertropical convergence zone, which is supported by stronger nonlinear horizontal momentum advection in the boundary layer. There is also twice as much tropical rainfall variance in the experiment with resolved deep convection than in the experiments with parameterized convection. All experiments show comparable precipitation variance associated with Kelvin waves; however, the experiment with resolved deep convection shows higher precipitation variance associated with westward propagating systems. Resolved deep convection also yields at least two orders of magnitude more frequent heavy rainfall rates (>2 mm hr−1) than the experiments with parameterized convection. A comparison of organized precipitation systems demonstrates that tropical convection organizes into linear systems that are associated with stronger and deeper cold pools and upgradient convective momentum fluxes when convection is resolved. In contrast, parameterized convection results in more circular systems, weaker cold pools, and downgradient convective momentum fluxes. These results suggest that simulations with parameterized convection are missing an important feedback loop between the mean state, convective organization, and meridional gradients of moisture and momentum.
Expanded North Pacific Subtropical Gyre and Heterodyne Expression During the Mid‐Pleistocene
Authors: Taylor S. P. , Patterson M. O. , Lam A. R. , Jones H. , Woodard S. C. , Habicht M. H. , Thomas E. K. , Grant G. R.
Published: April 2022

The Kuroshio Current (KC) and Kuroshio Current Extension (KCE) form a western boundary current as part of the North Pacific Subtropical Gyre. This current plays an important role in regulating weather and climate dynamics in the Northern Hemisphere in part by controlling the delivery of moisture to the lower atmosphere. Previous studies indicate the KCE responded dynamically across glacial and interglacial periods throughout the Pliocene‐Pleistocene. However, the response of the KCE during Pleistocene super‐interglacials has not been examined in detail. We present a ∼2.2 Ma record of X‐ray fluorescence elemental data from Ocean Drilling Program Hole 1207A and employ hierarchical clustering techniques to demonstrate paleoenvironmental changes around the KCE. Time‐frequency analysis identifies significant heterodyne frequencies, which suggests there were nonlinear interactions between high‐latitude and low‐latitude climate regulating expansion and contraction of the North Pacific Subtropical Gyre prior to the onset of the Mid‐Pleistocene Climate Transition (MPT). We observe two periods of elevated ln Ca/Ti, which may represent sustained warmth with northward migrations of the KCE in the northwestern Pacific. These intervals correspond to Marine Isotope Stages 29‐25, 15, and 11‐9 and occur around recent climatic transitions, the MPT and Mid‐Brunhes Event. Northward expansion of the subtropical gyre during these exceptionally warm interglacials would have delivered more heat and moisture to the high latitudes of the northwest Pacific. Furthermore, enhanced evaporation from the warm KCE vented to the lower atmosphere may have preconditioned the Northern Hemisphere for ice volume growth during two of the most recent periods of climate transition.
Thank You to Our 2021 Reviewers
Authors: Griffies Stephen M. , Blyth Eleanor Mary , Fan Jiwen , MacBean Natasha , Schneider Tapio
Published: April 2022

Key Point

The editors thank the 2021 peer reviewers
Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers
Authors: Jenkins Frank J. , Minas Tsion Z. , Tang Wei , Dorsey Tiffany H. , Ambs Stefan
Published: April 2022

Background

The dinucleotide germline variant, rs368234815-ΔG, in the IFNL4 gene (IFNL4-ΔG) has been associated with prostate cancer among men at increased risk of sexually transmitted infections and reported to impair viral clearance. Human herpesvirus 8 (HHV-8) seropositivity has been associated with prostate cancer in Tobago.

Methods

We examined whether the association of HHV-8 with prostate cancer is IFNL4-ΔG-dependent among 728 IFNL4-ΔG-genotyped cases and 813 genotyped population-based controls from the NCI-Maryland Prostate Cancer Case-Control study. Associations between HHV-8 and prostate cancer were assessed in multivariable unconditional logistic regression models. We calculated adjusted odds ratios (OR) and stratified the analysis into men harboring the IFNL4-ΔG-variant and non-carriers (ΔG/ΔG or ΔG/TT vs. TT/TT).

Results

HHV-8 seropositivity was higher in cases than controls (11% vs. 6%) and this association was restricted to carriers of the ΔG allele (OR 2.19: 95% CI:1.38–3.48) in both African American (OR 1.96; 95% CI:1.08–3.56) and European American men (OR 2.59; 95% CI:1.20–5.56).

Conclusions

HHV-8 seropositivity is associated with increased odds of prostate cancer in men harboring the IFNL4 rs368234815-ΔG variant. This study describes HHV-8 infection as a candidate prostate cancer risk factor in men with the IFNL4-ΔG genotype and supports the hypothesis that IFNL4-ΔG is a susceptibility factor that contributes to prostate cancer.
PRKDC promotes hepatitis B virus transcription through enhancing the binding of RNA Pol II to cccDNA
Authors: Fan Yao , Liang Yi , Liu Yu , Fan Hui
Published: April 2022

Hepatitis B virus infection remains a major health problem worldwide due to its high risk of liver failure and hepatocellular carcinoma. Covalently closed circular DNA (cccDNA), which is present as an individual minichromosome, serves as the template for transcription of all viral RNAs and pla ays critical role in viral persistence. Therefore, there is an urgent need to gain broader insight into the transcription regulation of cccDNA. Here, we combined a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) with an engineered ascorbate peroxidase 2 (APEX2) to identify cccDNA associated proteins systematically in living cells. By functional screening, we verified that protein kinase, DNA-activated, catalytic subunit (PRKDC) was an effective activator of HBV cccDNA transcription in HBV-infected HepG2-NTCP cells and primary human hepatocytes. Mechanismly, PRKDC interacted with POLR2A and POLR2B, the two largest subunits of RNA polymerase II (Pol II) and recruited Pol II to HBV cccDNA minichromosome in a kinase-dependent manner. PRKDC knockdown or inhibitor treatment significantly decreased the enrichment of POLR2A and POLR2B on cccDNA, as well as reducing the levels of cccDNA associated Pol II Ser5 and Ser2 phosphorylation, which eventually inhibited the HBV cccDNA activity. Collectively, these findings give us new insights into cccDNA transcription regulation, thus providing new potential targets for HBV treatment in patients.
JMJD2C mediates the MDM2/p53/IL5RA axis to promote CDDP resistance in uveal melanoma
Authors: Zhu Qi , Chen Han , Li Xiaoying , Wang Xi , Yan Hongtao
Published: April 2022

Chemotherapy resistance poses an obstacle for effective treatment of uveal melanoma. In this study, we aim to investigate the effects of jumonji domain containing 2C (JMJD2C)-mediated mouse double minute-2 homolog (MDM2)/p53/interleukin 5 receptor subunit alpha (IL5RA) axis on cisplatin (CDDP) resistance in uveal melanoma. RT-qPCR and Western blot assay were performed to determine their expression patterns in uveal melanoma cell line (MUM-2B) and CDDP-resistant cell line (MUM-2B/CDDP). The enrichment of H3K9me3 in MDM2 promoter region was examined by ChIP, and the binding between p53 and ubiquitin in MUM-2B cells testified by co-IP assay. Following overexpression or silencing of JMJD2C/MDM2/p53/IL5RA, the 50% concentration of inhibition (IC50) and the biological characteristics of MUM-2B and MUM-2B/CDDP cells were examined using CCK-8 assay, SA-β-gal staining, fluorescence-activated cell sorting analysis, and Transwell assay. Finally, the tumorigenicity of transplanted MUM-2B and MUM-2B/CDDP cells in nude mice was assessed. JMJD2C was documented to be highly expressed in uveal melanoma cells, promoting the CDDP resistance. Histone demethylase JMJD2C removed the H3K9me3 modification of MDM2 promoter, which promoted the expression of MDM2. MDM2 enhanced the IL5RA expression through stimulating the ubiquitination and degradation of p53, thus inducing CDDP resistance of uveal melanoma cells. Furthermore, the results of in vivo experiments revealed that JMJD2C mediated the MDM2/p53/IL5RA axis to expedite the growth of uveal melanoma and augment the CDDP resistance. Taken together, JMJD2C can induce histone demethylation to upregulate MDM2, thereby ubiquitinating p53 and upregulating IL5RA. As a consequence, CDDP resistance in uveal melanoma is ultimately accelerated.
A structural exposé of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop
Authors: Wang Huanchen , Perera Lalith , Jork Nikolaus , Zong Guangning , Riley Andrew M. , Potter Barry V. L. , Jessen Henning J. , Shears Stephen B.
Published: April 2022

Structural snapshots of protein/ligand complexes are a prerequisite for gaining atomic level insight into enzymatic reaction mechanisms. An important group of enzymes has been deprived of this analytical privilege: members of the protein tyrosine phosphatase (PTP) superfamily with catalytic WPD-loops lacking the indispensable general-acid/base within a tryptophan-proline-aspartate/glutamate context. Here, we provide the ligand/enzyme crystal complexes for one such PTP outlier: Arabidopsis thaliana Plant and Fungi Atypical Dual Specificity Phosphatase 1 (AtPFA-DSP1), herein unveiled as a regioselective and efficient phosphatase towards inositol pyrophosphate (PP-InsP) signaling molecules. Although the WPD loop is missing its canonical tripeptide motif, this structural element contributes to catalysis by assisting PP-InsP delivery into the catalytic pocket, for a choreographed exchange with phosphate reaction product. Subsequently, an intramolecular proton donation by PP-InsP substrate is posited to substitute functionally for the absent aspartate/glutamate general-acid. Overall, we expand mechanistic insight into adaptability of the conserved PTP structural elements.
An unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers
Authors: An Jing , Tang Shanliang , Hong Gaobo , Chen Wenlong , Chen Miaomiao , Song Jitao , Li Zhiliang , Peng Xiaojun , Song Fengling , Zheng Wen-Heng
Published: April 2022

The most common working mechanism of photodynamic therapy is based on high-toxicity singlet oxygen, which is called Type II photodynamic therapy. But it is highly dependent on oxygen consumption. Recently, Type I photodynamic therapy has been found to have better hypoxia tolerance to ease this restriction. However, few strategies are available on the design of Type I photosensitizers. We herein report an unexpected strategy to alleviate the limitation of traditional photodynamic therapy by biotinylation of three photosensitizers (two fluorescein-based photosensitizers and the commercially available Protoporphyrin). The three biotiylated photosensitizers named as compound 1, 2 and 3, exhibit impressive ability in generating both superoxide anion radicals and singlet oxygen. Moreover, compound 1 can be activated upon low-power white light irradiation with stronger ability of anion radicals generation than the other two. The excellent combinational Type I / Type II photodynamic therapy performance has been demonstrated with the photosensitizers 1. This work presents a universal protocol to provide tumor-targeting ability and enhance or trigger the generation of anion radicals by biotinylation of Type II photosensitizers against tumor hypoxia.
Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2
Authors: Israeli Ma’ayan , Finkel Yaara , Yahalom-Ronen Yfat , Paran Nir , Chitlaru Theodor , Israeli Ofir , Cohen-Gihon Inbar , Aftalion Moshe , Falach Reut , Rotem Shahar , Elia Uri , Nemet Ital , Kliker Limor , Mandelboim Michal , Beth-Din Adi , Israely Tomer , Cohen Ofer , Stern-Ginossar Noam , Bercovich-Kinori Adi
Published: April 2022

The global spread of SARS-CoV-2 led to major economic and health challenges worldwide. Revealing host genes essential for infection by multiple variants of SARS-CoV-2 can provide insights into the virus pathogenesis, and facilitate the development of novel therapeutics. Here, employing a genome-scale CRISPR screen, we provide a comprehensive data-set of cellular factors that are exploited by wild type SARS-CoV-2 as well as two additional recently emerged variants of concerns (VOCs), Alpha and Beta. We identified several host factors critical for SARS-CoV-2 infection, including various components belonging to the Clathrin-dependent transport pathway, ubiquitination, Heparan sulfate biogenesis and host phosphatidylglycerol biosynthesis. Comparative analysis of the different VOCs revealed the host factors KREMEN2 and SETDB1 as potential unique candidates required only to the Alpha variant. Furthermore, the analysis identified GATA6, a zinc finger transcription factor, as an essential proviral gene for all variants inspected. We show that GATA6 directly regulates ACE2 transcription and accordingly, is critical for SARS-CoV-2 cell entry. Analysis of clinical samples collected from SARS-CoV-2 infected individuals shows elevated levels of GATA6, suggesting a role in COVID-19 pathogenesis. Finally, pharmacological inhibition of GATA6 resulted in down-modulation of ACE2 and inhibition of viral infectivity. Overall, we show GATA6 may represent a target for the development of anti-SARS-CoV-2 therapeutic strategies and reaffirm the value of the CRISPR loss-of-function screens in providing a list of potential new targets for therapeutic interventions.
Modeling antiphase boundary energies of Ni3Al-based alloys using automated density functional theory and machine learning
Authors: Chen Enze , Tamm Artur , Wang Tao , Epler Mario E. , Asta Mark , Frolov Timofey
Published: April 2022

Antiphase boundaries (APBs) are planar defects that play a critical role in strengthening Ni-based superalloys, and their sensitivity to alloy composition offers a flexible tuning parameter for alloy design. Here, we report a computational workflow to enable the development of sufficient data to train machine-learning (ML) models to automate the study of the effect of composition on the (111) APB energy in Ni3Al-based alloys. We employ ML to leverage this wealth of data and identify several physical properties that are used to build predictive models for the APB energy that achieve a cross-validation error of 0.033 J m−2. We demonstrate the transferability of these models by predicting APB energies in commercial superalloys. Moreover, our use of physically motivated features such as the ordering energy and stoichiometry-based features opens the way to using existing materials properties databases to guide superalloy design strategies to maximize the APB energy.
An extended computational approach for point-defect equilibria in semiconductor materials
Authors: Ogawa Takafumi , Taguchi Ayako , Kuwabara Akihide
Published: April 2022

Concentrations of intrinsic and extrinsic point defects in crystalline materials with a bandgap are typically calculated in a constant-μ approach from defect formation energies based on density functional theory. In this work, calculations of thermal and charge equilibria among point defects are extended to a constant-N approach. The two approaches for point-defect equilibria are comparatively demonstrated in the application to Mg2Si doped with Li, Na, and Ag, which is a lightweight and environmentally friendly thermoelectric candidate material. Our results reveal the systematic behavior of defect and carrier concentrations. The dopant atoms form interstitial defects at similar concentrations to substitutional defects at the Mg sites, resulting in significantly reduced free-carrier concentrations compared to the expected values. The developed procedures could be utilized to find an optimal avenue for achieving higher carrier concentrations, e.g., with regard to annealing temperature and the concentration of dopant atoms, in various semiconductors and insulators.
Lipid level alteration in human and cellular models of alpha synuclein mutations
Authors: Avisar Hila , Guardia-Laguarta Cristina , Surface Matthew , Papagiannakis Nikos , Maniati Matina , Antonellou Roubina , Papadimitriou Dimitra , Koros Christos , Athanassiadou Aglaia , Przedborski Serge , Lerner Boaz , Stefanis Leonidas , Area-Gomez Estela , Alcalay Roy N.
Published: April 2022

Lipid profiles in biological fluids from patients with Parkinson’s disease (PD) are increasingly investigated in search of biomarkers. However, the lipid profiles in genetic PD remain to be determined, a gap of knowledge of particular interest in PD associated with mutant α-synuclein (SNCA), given the known relationship between this protein and lipids. The objective of this research is to identify serum lipid composition fromSNCAA53T mutation carriers and to compare these alterations to those found in cells and transgenic mice carrying the same genetic mutation. We conducted an unbiased lipidomic analysis of 530 lipid species from 34 lipid classes in serum of 30 participants withSNCAmutation with and without PD and 30 healthy controls. The primary analysis was done between 22 PD patients withSNCA+ (SNCA+/PD+) and 30 controls using machine-learning algorithms and traditional statistics. We also analyzed the lipid composition of human clonal-cell lines and tissue from transgenic mice overexpressing the sameSNCAmutation. We identified specific lipid classes that best discriminate betweenSNCA+/PD+ patients and healthy controls and found certain lipid species, mainly from the glycerophosphatidylcholine and triradylglycerol classes, that are most contributory to this discrimination. Most of these alterations were also present in human derived cells and transgenic mice carrying the same mutation. Our combination of lipidomic and machine learning analyses revealed alterations in glycerophosphatidylcholine and triradylglycerol in sera from PD patients as well as cells and tissues expressing mutant α-Syn. Further investigations are needed to establish the pathogenic significance of these α-Syn-associated lipid changes.
A highly photostable and bright green fluorescent protein
Authors: Hirano Masahiko , Ando Ryoko , Shimozono Satoshi , Sugiyama Mayu , Takeda Noriyo , Kurokawa Hiroshi , Deguchi Ryusaku , Endo Kazuki , Haga Kei , Takai-Todaka Reiko , Inaura Shunsuke , Matsumura Yuta , Hama Hiroshi , Okada Yasushi , Fujiwara Takahiro , Morimoto Takuya , Katayama Kazuhiko , Miyawaki Atsushi
Published: April 2022

The low photostability of fluorescent proteins is a limiting factor in many applications of fluorescence microscopy. Here we present StayGold, a green fluorescent protein (GFP) derived from the jellyfish Cytaeis uchidae. StayGold is over one order of magnitude more photostable than any currently available fluorescent protein and has a cellular brightness similar to mNeonGreen. We used StayGold to image the dynamics of the endoplasmic reticulum (ER) with high spatiotemporal resolution over several minutes using structured illumination microscopy (SIM) and observed substantially less photobleaching than with a GFP variant optimized for stability in the ER. Using StayGold fusions and SIM, we also imaged the dynamics of mitochondrial fusion and fission and mapped the viral spike proteins in fixed cells infected with severe acute respiratory syndrome coronavirus 2. As StayGold is a dimer, we created a tandem dimer version that allowed us to observe the dynamics of microtubules and the excitatory post-synaptic density in neurons. StayGold will substantially reduce the limitations imposed by photobleaching, especially in live cell or volumetric imaging.
Molecular spikes: a gold standard for single-cell RNA counting
Authors: Ziegenhain Christoph , Hendriks Gert-Jan , Hagemann-Jensen Michael , Sandberg Rickard
Published: April 2022

Single-cell sequencing methods rely on molecule-counting strategies to account for amplification biases, yet no experimental strategy to evaluate counting performance exists. Here, we introduce molecular spikes—RNA spike-ins containing built-in unique molecular identifiers (UMIs) that we use to identify critical experimental and computational conditions for accurate RNA counting in single-cell RNA-sequencing (scRNA-seq). Using molecular spikes, we uncovered impaired RNA counting in methods that were not informative for cellular RNA abundances due to inflated UMI counts. We further leverage molecular spikes to improve estimates of total endogenous RNA amounts in cells, and introduce a strategy to correct experiments with impaired RNA counting. The molecular spikes and the accompanying R package UMIcountR (https://github.com/cziegenhain/UMIcountR) will improve the validation of new methods, better estimate and adjust for cellular mRNA amounts and enable more indepth characterization of RNA counting in scRNA-seq.
Clinical target segmentation using a novel deep neural network: double attention Res-U-Net
Authors: Ashkani Chenarlogh Vahid , Shabanzadeh Ali , Ghelich Oghli Mostafa , Sirjani Nasim , Farzin Moghadam Sahar , Akhavan Ardavan , Arabi Hossein , Shiri Isaac , Shabanzadeh Zahra , Sanei Taheri Morteza , Kazem Tarzamni Mohammad
Published: April 2022

We introduced Double Attention Res-U-Net architecture to address medical image segmentation problem in different medical imaging system. Accurate medical image segmentation suffers from some challenges including, difficulty of different interest object modeling, presence of noise, and signal dropout throughout the measurement. The base line image segmentation approaches are not sufficient for complex target segmentation throughout the various medical image types. To overcome the issues, a novel U-Net-based model proposed that consists of two consecutive networks with five and four encoding and decoding levels respectively. In each of networks, there are four residual blocks between the encoder-decoder path and skip connections that help the networks to tackle the vanishing gradient problem, followed by the multi-scale attention gates to generate richer contextual information. To evaluate our architecture, we investigated three distinct data-sets, (i.e., CVC-ClinicDB dataset, Multi-site MRI dataset, and a collected ultrasound dataset). The proposed algorithm achieved Dice and Jaccard coefficients of 95.79%, 91.62%, respectively for CRL, and 93.84% and 89.08% for fetal foot segmentation. Moreover, the proposed model outperformed the state-of-the-art U-Net based model on the external CVC-ClinicDB, and multi-site MRI datasets with Dice and Jaccard coefficients of 83%, 75.31% for CVC-ClinicDB, and 92.07% and 87.14% for multi-site MRI dataset, respectively.
Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses
Authors: Ide Yutaro , Kitab Bouchra , Ito Nobumasa , Okamoto Riai , Tamura Yui , Matsui Takafumi , Sakoda Yoshihiro , Tsukiyama-Kohara Kyoko
Published: April 2022

Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) possess positive-sense single-stranded RNA genomes and an internal ribosomal entry site (IRES) element within their 5′-untranslated regions. To investigate the common host factors associated with these IRESs, we established cell lines expressing a bicistronic luciferase reporter plasmid containing an FMDV-IRES or CSFV-IRES element between theRenillaand firefly luciferase genes. First, we treated FMDV-IRES cells with the French maritime pine extract, Pycnogenol (PYC), and examined its suppressive effect on FMDV-IRES activity, as PYC has been reported to have antiviral properties. Next, we performed microarray analysis to identify the host factors that modified their expression upon treatment with PYC, and confirmed their function using specific siRNAs. We found that polycystic kidney disease 1-like 3 (PKD1L3) and ubiquitin-specific peptidase 31 (USP31) were associated with FMDV-IRES activity. Moreover, silencing of these factors significantly suppressed CSFV-IRES activity. Thus, PKD1L3 and USP31 are host factors associated with the functions of FMDV- and CSFV-IRES elements.
Investigation of optical and electrical properties of novel 4T all perovskite tandem solar cell
Authors: Moradbeigi Mahsa , Razaghi Mohammad
Published: April 2022

In this paper, a combined three-dimensional (3D) optical-electrical simulation of non-pb and flexible four-terminal (4T) all perovskite tandem solar cell (APTSC) is presented. In this structure, polyethylene terephthalate (PET) is used as substrates, while the top sub cell has a $$MAGeI_{3}$$

M
A
G
e

I
3

absorber layer and the bottom sub cell has a $$MASnI_{3}$$

M
A
S
n

I
3

absorber layer. This structure is used as a reference in this paper and the optical and electrical properties of it are investigated using the finite element method (FEM). It is shown that this structure has a total power conversion efficiency (PCE) of $$24.65\%$$

24.65
%

. Then, the elimination of the buffer layer and the addition of antireflection layer (ARL) strategies, as well as the use of periodic nano-texture patterns, are used to increase the reference structure’s total PCE. A free-buffer layer tandem device is presented to minimize the parasitic absorption. While the total PCE is improved by $$1.14\%$$

1.14
%

in this case, one of the fabrication steps is also eliminated. A plasma-polymer-fluorocarbon (PPFC) coating layer is suggested as ARL on the substrates of both sub cells to reduce reflection loss. With optimized these layers thickness, total PCE is increased by $$12.76\%$$

12.76
%

. Because the PPFC layer is hydrophobic, the top surface of two sub cells in this structure has self-cleaning characteristic. As a result, this device offers long-term moisture resistance. Finally, the best structure in terms of the maximum total PCE is presented by increasing optical path-length utilizing nano-photonic and nano-plasmonic structures. The final structure is offered as a 4T tandem solar cell (TSC) that is environmentally friendly, extremely flexible, and has self-cleaning capability, with a total PCE of $$30.14\%$$

30.14
%

, which is greater than the total PCE of the reference structure by $$22.27\%$$

22.27
%

.
Magnetic chitosan stabilized Cu(II)-tetrazole complex: an effective nanocatalyst for the synthesis of 3-imino-2-phenylisoindolin-1-one derivatives under ultrasound irradiation
Authors: Nasrollahzadeh Mahmoud , Shafiei Nasrin , Orooji Yasin
Published: April 2022

In the present research, a recyclable catalyst has been prepared via a simple approach using chitosan as a linear polysaccharide. This paper reports the synthesis of novel copper(II) complex of 5-phenyl-1H-tetrazole immobilized on magnetic chitosan (MCS@PhTet@Cu(II)) as an effective catalyst. Transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), vibrating sample magnetometer (VSM), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), and inductively coupled plasma mass spectrometry (ICP-MS) techniques were applied for the characterization of the catalyst. The catalytic activity of MCS@PhTet@Cu(II) was evaluated in the ultrasound-assisted synthesis of 3-imino-2-phenylisoindolin-1-one derivatives via the reaction between benzoyl chloride and arylcyanamides in ethanol at ambient temperature. Utilizing a wide variety of arylcyanamides under mild conditions, no use of toxic organic solvents, moderate reaction time, high yields along with catalyst excellent reusability and easy separation of the products without any tedious separation techniques, made this method a novel and simple process. The resulting heterogeneous catalyst showed valuable advantages such as easier work-up, better stability, and greater separation ability using an external magnet. The catalyst showed high efficacy and recyclability even after five cycles with no significant loss of its efficacy. The present methodology provides a path for the preparation of structurally diverse heterocyclic compounds, which may exhibit important biological activity.
Combined effects of handgrip strength and sensory impairment on the prevalence of cognitive impairment among older adults in Korea
Authors: Lee JuHee , Suh Yujin , Park Jungah , Kim Go-Un , Lee Sumi
Published: April 2022

Older adults commonly experience concurrent lower handgrip strength and sensory impairment. However, previous studies have analyzed the individual effects of either handgrip strength or sensory impairment on cognitive impairment. To address this gap, this study investigated the combined effects of handgrip strength and sensory impairment on cognitive impairment among older adults. In total, 2930 participants aged 65 and older were analyzed using 2014–2018 data from the Korean Longitudinal Study of Aging. Participants underwent assessments of handgrip strength (grip dynamometer), sensory impairment (self-reported responses), and cognitive impairment (Korean version of the Mini-Mental State Examination). Low handgrip strength, compared to normal handgrip strength, was associated with cognitive impairment. In participants with low handgrip strength, vision and hearing impairment were associated with cognitive impairment (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.06–1.75; OR 2.58, 95% CI 1.77–3.78, respectively) compared to those with normal handgrip strength. Participants with low handgrip strength and dual sensory impairment had the highest OR for cognitive impairment (OR 3.73, 95% CI 2.65–5.25). Due to the strong association of low handgrip strength and dual sensory impairment with cognitive impairment, people living with low handgrip strength and dual sensory impairment should be classified as a high-risk group for cognitive impairment and should be prioritized for interventions.
A hybrid machine learning approach for estimating the water-use efficiency and yield in agriculture
Authors: Dehghanisanij Hossein , Emami Hojjat , Emami Somayeh , Rezaverdinejad Vahid
Published: April 2022

This paper introduces the narrow strip irrigation (NSI) method and aims to estimate water-use efficiency (WUE) and yield in apple orchards under NSI in the Miandoab region located southeast of Lake Urmia using a machine learning approach. To perform the estimation, a hybrid method based on an adaptive neuro-fuzzy inference system (ANFIS) and seasons optimization (SO) algorithm was proposed. According to the irrigation and climate factors, six different models have been proposed to combine the parameters in the SO-ANFIS. The proposed method is evaluated on a test data set that contains information about apple orchards in Miandoab city from 2019 to 2021. The NSI model was compared with two popular irrigation methods including two-sided furrow irrigation (TSFI) and basin irrigation (BI) on benchmark scenarios. The results justified that the NSI model increased WUE by 1.90 kg/m3 and 3.13 kg/m3, and yield by 8.57% and 14.30% compared to TSFI and BI methods, respectively. The experimental results show that the proposed SO-ANFIS has achieved the performance of 0.989 and 0.988 in terms of R2 criterion in estimating WUE and yield of NSI irrigation method, respectively. The results confirmed that the SO-ANFIS outperformed the counterpart methods in terms of performance measures.
Drivers of genomic loss of heterozygosity in leiomyosarcoma are distinct from carcinomas
Authors: Seligson Nathan D. , Tang Joy , Jin Dexter X. , Bennett Monica P. , Elvin Julia A. , Graim Kiley , Hays John L. , Millis Sherri Z. , Miles Wayne O. , Chen James L.
Published: April 2022

Leiomyosarcoma (LMS) is a rare, aggressive, mesenchymal tumor. Subsets of LMS have been identified to harbor genomic alterations associated with homologous recombination deficiency (HRD); particularly alterations in BRCA2. Whereas genomic loss of heterozygosity (gLOH) has been used as a surrogate marker of HRD in other solid tumors, the prognostic or clinical value of gLOH in LMS (gLOH-LMS) remains poorly defined. We explore the genomic drivers associated with gLOH-LMS and their clinical import. Although the distribution of gLOH-LMS scores are similar to that of carcinomas, outside of BRCA2, there was no overlap with previously published gLOH-associated genes from studies in carcinomas. We note that early stage tumors with elevated gLOH demonstrated a longer disease-free interval following resection in LMS patients. Taken together, and despite similarities to carcinomas in gLOH distribution and clinical import, gLOH-LMS are driven by different genomic signals. Additional studies will be required to isolate and confirm the unique differences in biological factors driving these differences.
Wearable fitness tracker use in federally qualified health center patients: strategies to improve the health of all of us using digital health devices
Authors: Holko Michelle , Litwin Tamara R. , Munoz Fatima , Theisz Katrina I. , Salgin Linda , Jenks Nancy Piper , Holmes Beverly W. , Watson-McGee Pamelia , Winford Eboni , Sharma Yashoda
Published: April 2022

As the use of connected devices rises, an understanding of how digital health technologies can be used for equitable healthcare across diverse communities is needed. We surveyed 1007 adult patients at six Federally Qualified Health Centers regarding wearable fitness trackers. Findings indicate the majority interest in having fitness trackers. Barriers included cost and lack of information, revealing that broad digital health device adoption requires education, investment, and high-touch methods.
Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH
Authors: Parsons Andrea J. , Ophir Sabrina I. , Duty J. Andrew , Kraus Thomas A. , Stein Kathryn R. , Moran Thomas M. , Tortorella Domenico
Published: April 2022

Human cytomegalovirus (HCMV) is a β-herpesvirus that increases morbidity and mortality in immunocompromised individuals including transplant recipients and newborns. New anti-HCMV therapies are an urgent medical need for diverse patient populations. HCMV infection of a broad range of host tissues is dependent on the gH/gL/gO trimer and gH/gL/UL28/UL130/UL131A pentamer complexes on the viral envelope. We sought to develop safe and effective therapeutics against HCMV by generating broadly-neutralizing, human monoclonal antibodies (mAbs) from VelocImmune® mice immunized with gH/gL cDNA. Following high-throughput binding and neutralization screening assays, 11 neutralizing antibodies were identified with unique CDR3 regions and a high-affinity (KD 1.4-65 nM) to the pentamer complex. The antibodies bound to distinct regions within Domains 1 and 2 of gH and effectively neutralized diverse clinical strains in physiologically relevant cell types including epithelial cells, trophoblasts, and monocytes. Importantly, combined adminstration of mAbs with ganciclovir, an FDA approved antiviral, greatly limited virus dissemination. Our work identifies several anti-gH/gL mAbs and sheds light on gH neutralizing epitopes that can guide future vaccine strategies.
Automated causal inference in application to randomized controlled clinical trials
Authors: Wu Ji Q. , Horeweg Nanda , de Bruyn Marco , Nout Remi A. , Jürgenliemk-Schulz Ina M. , Lutgens Ludy C. H. W. , Jobsen Jan J. , van der Steen-Banasik Elzbieta M. , Nijman Hans W. , Smit Vincent T. H. B. M. , Bosse Tjalling , Creutzberg Carien L. , Koelzer Viktor H.
Published: April 2022

Randomized controlled trials (RCTs) are considered the gold standard for testing causal hypotheses in the clinical domain; however, the investigation of prognostic variables of patient outcome in a hypothesized cause–effect route is not feasible using standard statistical methods. Here we propose a new automated causal inference method (AutoCI) built on the invariant causal prediction (ICP) framework for the causal reinterpretation of clinical trial data. Compared with existing methods, we show that the proposed AutoCI allows one to clearly determine the causal variables of two real-world RCTs of patients with endometrial cancer with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remains consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis.
Perivascular tenascin C triggers sequential activation of macrophages and endothelial cells to generate a pro-metastatic vascular niche in the lungs
Authors: Hongu Tsunaki , Pein Maren , Insua-Rodríguez Jacob , Gutjahr Ewgenija , Mattavelli Greta , Meier Jasmin , Decker Kristin , Descot Arnaud , Bozza Matthias , Harbottle Richard , Trumpp Andreas , Sinn Hans-Peter , Riedel Angela , Oskarsson Thordur
Published: April 2022

Disseminated cancer cells frequently lodge near vasculature in secondary organs. However, our understanding of the cellular crosstalk invoked at perivascular sites is still rudimentary. Here, we identify intercellular machinery governing formation of a pro-metastatic vascular niche during breast cancer colonization in the lung. We show that specific secreted factors, induced in metastasis-associated endothelial cells (ECs), promote metastasis in mice by enhancing stem cell properties and the viability of cancer cells. Perivascular macrophages, activated via tenascin C (TNC) stimulation of Toll-like receptor 4 (TLR4), were shown to be crucial in niche activation by secreting nitric oxide (NO) and tumor necrosis factor (TNF) to induce EC-mediated production of niche components. Notably, this mechanism was independent of vascular endothelial growth factor (VEGF), a key regulator of EC behavior and angiogenesis. However, targeting both macrophage-mediated vascular niche activation and VEGF-regulated angiogenesis resulted in added potency to curb lung metastasis in mice. Together, our findings provide mechanistic insights into the formation of vascular niches in metastasis.
Towards practical and robust DNA-based data archiving using the yin–yang codec system
Authors: Ping Zhi , Chen Shihong , Zhou Guangyu , Huang Xiaoluo , Zhu Sha Joe , Zhang Haoling , Lee Henry H. , Lan Zhaojun , Cui Jie , Chen Tai , Zhang Wenwei , Yang Huanming , Xu Xun , Church George M. , Shen Yue
Published: April 2022

DNA is a promising data storage medium due to its remarkable durability and space-efficient storage. Early bit-to-base transcoding schemes have primarily pursued information density, at the expense of introducing biocompatibility challenges or decoding failure. Here we propose a robust transcoding algorithm named the yin–yang codec, using two rules to encode two binary bits into one nucleotide, to generate DNA sequences that are highly compatible with synthesis and sequencing technologies. We encoded two representative file formats and stored themin vitroas 200 nt oligo pools andin vivoas a ~54 kbps DNA fragment in yeast cells. Sequencing results show that the yin–yang codec exhibits high robustness and reliability for a wide variety of data types, with an average recovery rate of 99.9% above 104molecule copies and an achieved recovery rate of 87.53% at ≤102copies. Additionally, thein vivostorage demonstration achieved an experimentally measured physical density close to the theoretical maximum.