bluuebunny/crossref_metadata_2025 huggingface dataset:
Issue Voting and Government Responsiveness to Policy Preferences
Authors: Guntermann Eric , Persson Mikael
Published: May 2021

Does citizens’ voting behavior influence government policy? Conventional models of democratic representation assume that issue voting by citizens induces government responsiveness to citizens’ preferences. However, existing research has not tested whether voting behavior makes any difference to responsiveness. We present a theoretical model of issue voting and policy responsiveness. We leverage Swedish election study panels and a corresponding dataset on policy implementation to empirically evaluate the influence of issue voting on the adoption by governments of popular policies. We find that parties that enter government are more likely to implement popular policies if supporters of a policy shift their votes towards those parties. Thus, issue voting can lead to government responsiveness as long as it does not force parties to be inconsistent with their prior positions.
SOX9-induced Generation of Functional Astrocytes Supporting Neuronal Maturation in an All-human System
Authors: Neyrinck Katrien , Van Den Daele Johanna , Vervliet Tim , De Smedt Jonathan , Wierda Keimpe , Nijs Melissa , Vanbokhoven Tom , D’hondt Astrid , Planque Mélanie , Fendt Sarah-Maria , Shih Pei-Yu , Seibt Frederik , Almenar Juan Pita , Kreir Mohamed , Kumar Devesh , Broccoli Vania , Bultynck Geert , Ebneth Andreas , Cabrera-Socorro Alfredo , Verfaillie Catherine
Published: May 2021

Astrocytes, the main supportive cell type of the brain, show functional impairments upon ageing and in a broad spectrum of neurological disorders. Limited access to human astroglia for pre-clinical studies has been a major bottleneck delaying our understanding of their role in brain health and disease. We demonstrate here that functionally mature human astrocytes can be generated by SOX9 overexpression for 6 days in pluripotent stem cell (PSC)-derived neural progenitor cells. Inducible (i)SOX9-astrocytes display functional properties comparable to primary human astrocytes comprising glutamate uptake, induced calcium responses and cytokine/growth factor secretion. Importantly, electrophysiological properties of iNGN2-neurons co-cultured with iSOX9-astrocytes are indistinguishable from gold-standard murine primary cultures. The high yield, fast timing and the possibility to cryopreserve iSOX9-astrocytes without losing functional properties makes them suitable for scaled-up production for high-throughput analyses. Our findings represent a step forward to an all-human iPSC-derived neural model for drug development in neuroscience and towards the reduction of animal use in biomedical research.

Graphical Abstract
Szklary nickel deposit — a review and introduction to attempts in hydrometallurgical processing
Authors: Kaczan Wojciech , Kudełko Jan , Wirth Herbert
Published: May 2021

Szklary Massif is situated about 60 km from Wrocław (southwestern Poland) and around 7 km from Ząbkowice Śląskie. The history of raw materials in this region started in the fifteenth century with the discovery of precious minerals like chrysoprase, chalcedony, and opal. The exploitation of nickel ore in this region started in the nineteenth century and was conducted with few stops until 1983. The remaining 17.21 mln mg of ore with 125,000 mg of nickel might be a chance to satisfy rising demand for raw materials used to develop electromobility. One of the crucial aspects regarding possible investment is the processing of ore. The pilot tests show the efficient use of heap leaching. The authors provide the future project in Szklary within the framework of circular economy.
Correction to: Isoprenylated Flavonoids as Cav3.1 Low Voltage-Gated Ca2+ Channel Inhibitors from Salvia digitaloides
Authors: Zhao Jian-Jun , Li Song-Yu , Xia Fan , Hu Ya-Li , Nian Yin , Xu Gang
Published: May 2021

A correction to this paper has been published: https://doi.org/10.1007/s13659-021-00308-x
Disability as a Problem of Humanity in Scottish Enlightenment Thought
Authors: Cleall Esme , Gust Onni
Published: May 2021

This article makes a case that disability, particularly visual, hearing, and speech impairments, played a significant role in Scottish Enlightenment thought. Focusing on the work of Dugald Stewart, and in particular on his essay ‘Some account of a boy born blind and deaf’, we argue that disability was a deep preoccupation of Scottish Enlightenment thinkers who used it as a test case for various important philosophical questions including those concerning ‘human nature’ and the limits of humanity. The article starts by situating the philosophical debate in the context of lived experiences of, and proximity to, impairment. The second part offers a close reading of Stewart's text ‘Some account’, about James Mitchell, a fourteen-year-old deafblind boy living in the Scottish Highlands. The third part examines how disability operated in relation to other hierarchies of difference that have been demonstrated to have been central to Enlightenment thought, in particular that of race. Overall, the contribution this article makes is to introduce disability as an important, if currently overlooked, category in Scottish Enlightenment thought that needs further investigation.
Iran's “Self-Deprecating Modernity”: Toward Decolonizing Collective Self-Critique
Authors: Abedinifard Mostafa
Published: May 2021

Extant studies of Iranian nationalism accentuate the self-aggrandizing side of Iranian modernity, mainly achieved through, and informing, a process of otherizing certain non-Persians/Iranians, particularly the Arabs. I argue that equally important to understanding Iranian modernity is its lesser recognized, shameful and self-demeaning face, as manifested through a simultaneous 19th-century discourse, which I call “self-deprecating modernity.” This was an often self-ridiculing and shame-inducing, sometimes satirical, discourse featuring an emotion-driven and self-Orientalizing framework that developed out of many mid-nineteenth-century Iranian modernists’ obsessions with Europe's gaze; with self-surveillance; and with the perceived humiliation of Iranians through the ridiculing laughter of Other (especially European) nations at Iran's and Iranians’ expense. To explore this discourse, I re-examine the works of three pre-constitutionalist thinkers and writers within the broader sociopolitical context of late Qajar Iran, surveying their perspectives on shame, embarrassment, and ridiculing laughter, and showing how they were significantly informed by, while also helping to form, self-deprecating modernity. Given the strong, self-colonizing presumptions of this discourse, I conclude the article with a stress on the importance of re-exploring collective self-critical practices in modern Iranian history, culture, and literature with an eye toward decolonizing self-criticism.
Consumer preferences for low-salt foods: a Danish case study based on a comprehensive supermarket intervention
Authors: Denver Sigrid , Christensen Tove , Nordström Jonas
Published: May 2021

Objective:

The objective is to analyse Danish consumers’ attitudes to buying food with reduced salt content.

Design:

The study is based on a comprehensive store intervention that included 114 stores belonging to the same supermarket chain. Three different salt claims were tested for 8 weeks on six test products within the categories bread, cornflakes and frozen pizzas. Scanner data were supplemented with 134 brief interviews with consumers in nine selected stores.

Setting:

Stores spread across Denmark.

Participants:

Consumers who buy food in the stores.

Results:

Statistical regression analyses of the scanner data indicated that none of the three claims significantly affected demand for any of the test products. The interviews confirmed that many consumers were more focused on other elements of the official dietary advice than reduced salt consumption, such as eating plenty of vegetables, choosing products with whole grains and reducing their intake of sugar and fat.

Conclusions:

Overall, both the scanner data and the interviews pointed in the same direction, towards the conclusion that salt content is often a secondary factor when Danish consumers make dietary choices.
Equitable Exchange: A Framework for Diversity and Inclusion in the Geosciences
Authors: Harris L. A. , Garza C. , Hatch M. , Parrish J. , Posselt J. , Alvarez Rosario J. P. , Davidson E. , Eckert G. , Wilson Grimes K. , Garcia J. E. , Haacker R. , Horner‐Devine M. C. , Johnson A. , Lemus J. , Prakash A. , Thompson L. , Vitousek P. , Martin Bras M. P. , Reyes K.
Published: May 2021

We highlight a mechanism for the coproduction of research with local communities as a means of elevating the social relevance of the geosciences, increasing the potential for broader and more diverse participation. We outline the concept of an “Equitable Exchange” as an ethical framework guiding these interactions. This principled research model emphasizes that “currencies”—the rewards and value from participating in research—may differ between local communities and geoscientists. For those engaged in this work, an Equitable Exchange emboldens boundary spanning geoscientists to bring their whole selves to the work, providing a means for inclusive climates and rewarding cultural competency.
Activation of transmembrane receptor tyrosine kinase DDR1-STAT3 cascade by extracellular matrix remodeling promotes liver metastatic colonization in uveal melanoma
Authors: Dai Wei , Liu Shenglan , Wang Shubo , Zhao Li , Yang Xiao , Zhou Jingfeng , Wang Yun , Zhang Jing , Zhang Ping , Ding Ke , Li Yangqiu , Pan Jingxuan
Published: May 2021

Colonization is believed a rate-limiting step of metastasis cascade. However, its underlying mechanism is not well understood. Uveal melanoma (UM), which is featured with single organ liver metastasis, may provide a simplified model for realizing the complicated colonization process. Because DDR1 was identified to be overexpressed in UM cell lines and specimens, and abundant pathological deposition of extracellular matrix collagen, a type of DDR1 ligand, was noted in the microenvironment of liver in metastatic patients with UM, we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver. We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver. Mechanistically, UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells (qHSCs) into activated HSCs (aHSCs) which secreted collagen type I. Such a remodeling of extracellular matrix, in turn, activated DDR1, strengthening survival through upregulating STAT3-dependent Mcl-1 expression, enhancing stemness via upregulating STAT3-dependent SOX2, and promoting clonogenicity in cancer cells. Targeting DDR1 by using 7rh, a specific inhibitor, repressed proliferation and survival in vitro and in vivo outgrowth. More importantly, targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice. In conclusion, targeting DDR1 signaling and TGF-β signaling may be a novel approach to diminish hepatic metastasis in UM.
FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
Authors: Angus Steven P. , Stuhlmiller Timothy J. , Mehta Gaurav , Bevill Samantha M. , Goulet Daniel R. , Olivares-Quintero J. Felix , East Michael P. , Tanioka Maki , Zawistowski Jon S. , Singh Darshan , Sciaky Noah , Chen Xin , He Xiaping , Rashid Naim U. , Chollet-Hinton Lynn , Fan Cheng , Soloway Matthew G. , Spears Patricia A. , Jefferys Stuart , Parker Joel S. , Gallagher Kristalyn K. , Forero-Torres Andres , Krop Ian E. , Thompson Alastair M. , Murthy Rashmi , Gatza Michael L. , Perou Charles M. , Earp H. Shelton , Carey Lisa A. , Johnson Gary L.
Published: May 2021

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.
Holocene polynya dynamics and their interaction with oceanic heat transport in northernmost Baffin Bay
Authors: Jackson Rebecca , Kvorning Anna Bang , Limoges Audrey , Georgiadis Eleanor , Olsen Steffen M. , Tallberg Petra , Andersen Thorbjørn J. , Mikkelsen Naja , Giraudeau Jacques , Massé Guillaume , Wacker Lukas , Ribeiro Sofia
Published: May 2021

Baffin Bay hosts the largest and most productive of the Arctic polynyas: the North Water (NOW). Despite its significance and active role in water mass formation, the history of the NOW beyond the observational era remains poorly known. We reconcile the previously unassessed relationship between long-term NOW dynamics and ocean conditions by applying a multiproxy approach to two marine sediment cores from the region that, together, span the Holocene. Declining influence of Atlantic Water in the NOW is coeval with regional records that indicate the inception of a strong and recurrent polynya from ~ 4400 yrs BP, in line with Neoglacial cooling. During warmer Holocene intervals such as the Roman Warm Period, a weaker NOW is evident, and its reduced capacity to influence bottom ocean conditions facilitated northward penetration of Atlantic Water. Future warming in the Arctic may have negative consequences for this vital biological oasis, with the potential knock-on effect of warm water penetration further north and intensified melt of the marine-terminating glaciers that flank the coast of northwest Greenland.
Artificial insemination and parthenogenesis in the whitespotted bamboo shark Chiloscyllium plagiosum
Authors: Wyffels Jennifer T. , Adams Lance M. , Bulman Frank , Fustukjian Ari , Hyatt Michael W. , Feldheim Kevin A. , Penfold Linda M.
Published: May 2021

Non-lethal methods for semen collection from elasmobranchs to better understand species reproduction has accompanied the development of artificial insemination. Ejaculates (n = 82) collected from whitespotted bamboo sharksChiloscyllium plagiosum(n = 19) were assessed and cold-stored raw or extended at 4 °C. Females (n = 20) were inseminated with fresh or 24–48 h cold-stored raw or extended semen and paternity of offspring determined with microsatellite markers. Insemination of females with fresh semen (n = 10) resulted in 80 hatchlings and 27.6% fertility. Insemination of females with semen cold-stored 24 h (n = 4) and 48 h (n = 1) semen resulted in 17 hatchlings and fertilization rates of 28.1% and 7.1% respectively. Two females inseminated with fresh or cold-stored semen laid eggs that hatched from fertilization and parthenogenesis within the same clutch. Parthenogenesis rate for inseminated females was 0.71%. Results demonstrate artificial insemination with cold-stored semen can provide a strategy for transport of male genetics nationally and internationally, precluding the need to transport sharks. Production of parthenotes in the same clutch as sexually fertilized eggs highlights the prevalence of parthenogenesis in whitespotted bamboo sharks and poses important considerations for population management.
Optical and thermal properties of edible coatings for application in solar drying
Authors: López-Ortiz A. , Pacheco Pineda I. Y. , Méndez-Lagunas L. L. , Balbuena Ortega A. , Guerrero Martínez Laura , Pérez-Orozco J. P. , del Río J. A. , Nair P. K.
Published: May 2021

Solar drying is a sustainable process that may impact the quality of dried food. This is because, pigments contained in food are sensitive to sunlight, and exposure to ultraviolet radiation can affect them. We applied biopolymer-based coatings on strawberry, from hydro-colloidal solutions of Opuntia ficus indica-mucilage, fenugreek, xanthan gum, gum Arabic, and guar gum to evaluate their potential use as UV filters for solar drying of food. Thermal properties and the optical transmittance, absorbance and reflectance of the coatings were measured to assess their influence on food-sunlight interaction. During the drying experiments, the moisture content, total anthocyanins (TA), and total phenolic compounds (TPC) were measured. Optical and thermal properties are influenced by the biopolymer-based coatings. Also, the optical properties are influenced by the coating thickness. The differences in optical and thermal properties influence the drying process. Differences exist in the drying rate for strawberry slices with coating, compared with those without the coatings. In general, the TA and TPC content in the product are better preserved under solar drying than in control experiments done in a drying oven. A partial transmittance of solar UV radiation is recommended to obtain increased TA and TPC contents in the dried product.
Development of a multiplex mass spectrometry method for simultaneous quantification of urinary proteins related to respiratory health
Authors: Nauwelaerts Sarah J. D. , Roosens Nancy H. C. , Bernard Alfred , De Keersmaecker Sigrid C. J. , De Cremer Koen
Published: May 2021

Respiratory health of children is a health priority. Club cell protein (CC16) is an interesting biomarker of lung diseases and adverse effects towards the airway epithelium integrity. Osteopontin (OPN) and nuclear factor-kappa B (NF-κB) also play a role in respiratory health. The use of urine as biomarker source is useful in studies involving children but necessitates proper adjustment for physiological confounders influencing the urinary excretion, potentially characterized with beta-2-microglobulin (β2M), retinol binding protein 4 (RBP4) or myoglobin (MYO), as well as adjustment for possible renal dysfunction, characterized by human serum albumin (HSA). The simultaneous quantification of all these proteins in urine could facilitate children’s health monitoring. A multiple reaction monitoring method (MRM) was developed and validated for the relative quantification of the seven mentioned urinary proteins. A total of nine proteotypic peptides were selected and used for the relative quantification of the seven proteins. The MRM method was completely validated for all proteins and partially for OPN. LOQ’s ranged from 0.3 to 42.8 ng/ml, a good reproducibility and a good linearity were obtained across the analytical measurement range (r2 > 0.98). The method yielded varying correlations (r2 of 0.78, 0.71, 0.34 and 0.15 for CC16, β2M, RBP4 and HSA respectively) with available immunoassay data. It also allowed the identification and successful quantification of β2M and RBP4 as a protein candidate for adjustment of renal handling and dysfunction. All proteins were detected in the urine samples except for MYO and NF-κB. Our validated MRM-method is able to simultaneously quantify in urine biomarkers of airway epithelium integrity and biomarkers of variation in renal function and urinary dilution. This will allow to investigate further in future studies if urine can be used as a good surrogate source for biomarkers of airway epithelium integrity, and to understand the complex relationship between cause and effect in children’s respiratory health monitoring.
Grain size dependent photoresponsivity in GaAs films formed on glass with Ge seed layers
Authors: Nishida T. , Igura K. , Imajo T. , Suemasu T. , Toko K.
Published: May 2021

The strong correlation between grain size and photoresponsivity in polycrystalline GaAs films on glass was experimentally demonstrated using Ge seed layers with a wide range of grain sizes (1‒330 μm). The crystal evaluations using Raman spectroscopy, scanning electron microscopy, electron backscatter diffraction, and transmission electron microscopy revealed that 500-nm-thick GaAs films epitaxially grown from the Ge seed layers at 550 °C inherited the grain boundaries and crystal orientations in Ge. With increasing grain size, the photoresponsivity corresponding to GaAs increased from 0.01 to 3 A W−1 under a bias voltage of 0.3 V. The maximum value approached that of the GaAs film formed simultaneously on a single-crystal Ge wafer, indicating the high potential of the large-grained GaAs film. Knowledge gained from this study will be essential for designing advanced solar cells based on polycrystalline III–V compound semiconductors using inexpensive substrates.
Kinetics of Cu, Pb and Zn removal during soil flushing with washing agents derived from sewage sludge
Authors: Klik Barbara , Gusiatin Zygmunt M. , Kulikowska Dorota
Published: May 2021

This paper presents the first tests of Cu (7875 mg/kg), Pb (1414 mg/kg) and Zn (566 mg/kg) removal from contaminated soil with sewage-sludge–derived washing agents (SS_WAs) (dissolved organic matter, DOM; soluble humic-like substances, HLS; soluble humic substances, SHS) and Na2EDTA (as a standard benchmark) in column experiments. Flow rates of 0.5 ml/min and 1 ml/min were used. Using a 1. order kinetic model, the kinetic constant (k), the maximum concentrations of each metal removed (Cmax), and the initial rates of metal removal (r) were established. At both flow rates, stable flow velocity was maintained for approximately eight pore volumes, for flushing times of 8 h (1.0 ml/min) and 16 h (0.5 ml/min). Although the flow rate did not influence k, it influenced Cmax: at 1 ml/min, Cmax values were higher than at 0.5 ml/min. For Cu and Zn, but not Pb, k was about twofold higher with Na2EDTA than with SS_WAs. Although Na2EDTA gave the highest kCu, Cmax,Cu was highest with DOM (Na2EDTA, 66%; DOM 73%). For Pb removal, HLS was the most effective SS_WA (77%; Na2EDTA was 80% effective). kZn was about twofold higher with Na2EDTA than with SS_WAs. Cmax,Zn was highest with HLS. The quick mobilization of Cu, Pb and Zn with most of the WAs corresponded to efficient metal removal from the exchangeable (F1) fraction.
Magnetic reversal modes in cylindrical nanostructures: from disks to wires
Authors: Proenca Mariana P. , Rial Javier , Araujo Joao P. , Sousa Celia T.
Published: May 2021

Cylindrical magnetic nanowires are key elements of fast-recording and high-density 3D-storage devices. The accurate tuning of the magnetization processes at the nanoscale is crucial for the development of future nano-devices. Here, we analyzed the magnetization of Ni nanostructures with 15–100 nm in diameter and 12–230 nm in length and compared our results with experimental data for periodic arrays. Our modelling led to a phase diagram of the reversal modes where the presence of a critical diameter (d ≈ 30 nm) triggered the type of domain wall (DW) formed (transverse or vortex); while a critical length (L ≈ 100 nm) determined the number of DWs nucleated. Moreover, vortex-DWs originated from 3D skyrmion tubes, reported as one of the best configurations for storage devices. By increasing the diameter and aspect-ratio of nanowires with L > 100 nm, three reversal modes were observed: simultaneous propagation of two vortex-DWs; propagation of one vortex-DW; or spiral rotation of both DWs through “corkscrew” mechanism. Only for very low aspect-ratios (nanodisks), no skyrmion tubes were observed and reversal occurred by spiral rotation of one vortex-DW. The broad range of nanostructures studied allowed the creation of a complete phase diagram, highly important for future choice of nanoscaled dimensions in the development of novel nano-devices.
Validity of different copeptin assays in the differential diagnosis of the polyuria-polydipsia syndrome
Authors: Sailer Clara Odilia , Refardt Julie , Blum Claudine Angela , Schnyder Ingeborg , Molina-Tijeras Jose Alberto , Fenske Wiebke , Christ-Crain Mirjam
Published: May 2021

The aim of this study was to correlate three commercially available copeptin assays and their diagnostic accuracy in the differential diagnosis of the polyuria-polydipsia syndrome. Analyzed data include repeated copeptin measures of 8 healthy volunteers and 40 patients with polyuria-polydipsia syndrome undergoing osmotic stimulation and of 40 patients hospitalized with pneumonia. Copeptin was measured using the automated Brahms KRYPTOR, the manual Brahms LIA and the manual Cloud Clone ELISA assay. Primary outcome was the interrater correlation coefficient (ICC) and diagnostic accuracy in the polyuria-polydipsia syndrome of the three assays. In healthy volunteers, there was a moderate correlation for the KRYPTOR and LIA (ICC 0.74; 95% CI 0.07 to 0.91), and a poor correlation for the KRYPTOR and ELISA (ICC 0.07; 95% CI − 0.06 to 0.29), as for the LIA and ELISA (ICC 0.04; 95% CI − 0.04 to 0.17). The KRYPTOR had the highest diagnostic accuracy (98% (95% CI 83 to100)), comparable to the LIA (88% (95% CI 74 to 100)), while the ELISA had a poor diagnostic accuracy (55% (95% CI 34 to 68)) in the differential diagnosis of the polyuria-polydipsia syndrome. The KRYPTOR and LIA yield comparable copeptin concentrations and high diagnostic accuracy, while the ELISA correlates poorly with the other two assays and shows a poor diagnostic accuracy for polyuria-polydipsia patients. The current copeptin cut-off is valid for the KRYPTOR and LIA assay. Our results indicate that interpretation with other assays should be performed with caution and separate validation studies are required before their use in differentiating patients with polyuria-polydipsia syndrome.

Trial registration: NCT02647736 January 6, 2016/NCT01940614 September 12, 2013/NCT00973154 September 9, 2009.
Multiview deconvolution approximation multiphoton microscopy of tissues and zebrafish larvae
Authors: Kapsokalyvas Dimitrios , Rosas Rodrigo , Janssen Rob W. A. , Vanoevelen Jo M. , Nabben Miranda , Strauch Martin , Merhof Dorit , van Zandvoort Marc A. M. J.
Published: May 2021

Imaging in three dimensions is necessary for thick tissues and small organisms. This is possible with tomographic optical microscopy techniques such as confocal, multiphoton and light sheet microscopy. All these techniques suffer from anisotropic resolution and limited penetration depth. In the past, Multiview microscopy—imaging the sample from different angles followed by 3D image reconstruction—was developed to address this issue for light sheet microscopy based on fluorescence signal. In this study we applied this methodology to accomplish Multiview imaging with multiphoton microscopy based on fluorescence and additionally second harmonic signal from myosin and collagen. It was shown that isotropic resolution was achieved, the entirety of the sample was visualized, and interference artifacts were suppressed allowing clear visualization of collagen fibrils and myofibrils. This method can be applied to any scanning microscopy technique without microscope modifications. It can be used for imaging tissue and whole mount small organisms such as heart tissue, and zebrafish larva in 3D, label-free or stained, with at least threefold axial resolution improvement which can be significant for the accurate quantification of small 3D structures.
Predicting distribution of malaria vector larval habitats in Ethiopia by integrating distributed hydrologic modeling with remotely sensed data
Authors: Jiang Ai-Ling , Lee Ming-Chieh , Zhou Guofa , Zhong Daibin , Hawaria Dawit , Kibret Solomon , Yewhalaw Delenasaw , Sanders Brett F. , Yan Guiyun , Hsu Kuolin
Published: May 2021

Larval source management has gained renewed interest as a malaria control strategy in Africa but the widespread and transient nature of larval breeding sites poses a challenge to its implementation. To address this problem, we propose combining an integrated high resolution (50 m) distributed hydrological model and remotely sensed data to simulate potential malaria vector aquatic habitats. The novelty of our approach lies in its consideration of irrigation practices and its ability to resolve complex ponding processes that contribute to potential larval habitats. The simulation was performed for the year of 2018 using ParFlow-Common Land Model (CLM) in a sugarcane plantation in the Oromia region, Ethiopia to examine the effects of rainfall and irrigation. The model was calibrated using field observations of larval habitats to successfully predict ponding at all surveyed locations from the validation dataset. Results show that without irrigation, at least half of the area inside the farms had a 40% probability of potential larval habitat occurrence. With irrigation, the probability increased to 56%. Irrigation dampened the seasonality of the potential larval habitats such that the peak larval habitat occurrence window during the rainy season was extended into the dry season. Furthermore, the stability of the habitats was prolonged, with a significant shift from semi-permanent to permanent habitats. Our study provides a hydrological perspective on the impact of environmental modification on malaria vector ecology, which can potentially inform malaria control strategies through better water management.
A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
Authors: Diene Seydina M. , Pinault Lucile , Baron Sophie Alexandra , Azza Saïd , Armstrong Nicholas , Hadjadj Linda , Chabrière Eric , Rolain Jean-Marc , Pontarotti Pierre , Raoult Didier
Published: May 2021

Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one of the most clinically important antibiotics, thienamycin is encoded by a thienamycin gene cluster composed of 22 genes (thnA to thnV) from S. cattleya NRRL 8057 genome. Interestingly, the role of all thn-genes has been experimentally demonstrated in the thienamycin biosynthesis, except thnS, despite its annotation as putative β-lactamase. Here, we expressed thnS gene and investigated its activities against various substrates. Our analyses revealed that ThnS belonged to the superfamily of metallo-β-lactamase fold proteins. Compared to known β-lactamases such as OXA-48 and NDM-1, ThnS exhibited a lower affinity and less efficiency toward penicillin G and cefotaxime, while imipenem is more actively hydrolysed. Moreover, like most MBL fold enzymes, additional enzymatic activities of ThnS were detected such as hydrolysis of ascorbic acid, single strand DNA, and ribosomal RNA. ThnS appears as a MBL enzyme with multiple activities including a specialised β-lactamase activity toward imipenem. Thus, like toxin/antitoxin systems, the role of thnS gene within the thienamycin gene cluster appears as an antidote against the produced thienamycin.
Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer
Authors: Ueda Takashi , Shiraishi Takumi , Ito Saya , Ohashi Munehiro , Matsugasumi Toru , Yamada Yasuhiro , Fujihara Atsuko , Hongo Fumiya , Okihara Koji , Ukimura Osamu
Published: May 2021

The objective of this study was to compare the efficacy of abiraterone acetate with that of bicalutamide in combination with gonadotropin-releasing hormone (GnRH) antagonist treatment for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). A total of 149 patients with mHSPC who underwent treatment at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) with a GnRH antagonist (degarelix) (group A), and 99 patients were administered bicalutamide (80 mg/day) with a GnRH antagonist (group B). The prostate-specific antigen (PSA) progression-free survival (PSA-PFS) was significantly longer in group A than in group B. Abiraterone acetate therapy and Gleason score were significant independent factors of PSA-PFS. Using propensity score matching, 56 matched patients were obtained. The PSA-PFS (p < 0.001) and overall survival (OS) (p = 0.0071) of patients with high-risk mHSPC were significantly longer in group A of matched patients. Abiraterone acetate therapy and Gleason score were significant independent factors for PSA-PFS in matched patients. The PSA-PFS and OS of patients treated with abiraterone acetate in combination with a GnRH antagonist were significantly better than those treated with bicalutamide.
Differential response to scrambler therapy by neuropathic pain phenotypes
Authors: Min Young Gi , Baek Hyun Seok , Lee Kyoung-Min , Hong Yoon-Ho
Published: May 2021

Scrambler therapy is a noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory (NPSI) profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, − 15%; 95% CI − 28% to − 2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering based on the NPSI profiles partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the neuropathic pain phenotypes, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.
An artificial intelligence system for predicting the deterioration of COVID-19 patients in the emergency department
Authors: Shamout Farah E. , Shen Yiqiu , Wu Nan , Kaku Aakash , Park Jungkyu , Makino Taro , Jastrzębski Stanisław , Witowski Jan , Wang Duo , Zhang Ben , Dogra Siddhant , Cao Meng , Razavian Narges , Kudlowitz David , Azour Lea , Moore William , Lui Yvonne W. , Aphinyanaphongs Yindalon , Fernandez-Granda Carlos , Geras Krzysztof J.
Published: May 2021

During the coronavirus disease 2019 (COVID-19) pandemic, rapid and accurate triage of patients at the emergency department is critical to inform decision-making. We propose a data-driven approach for automatic prediction of deterioration risk using a deep neural network that learns from chest X-ray images and a gradient boosting model that learns from routine clinical variables. Our AI prognosis system, trained using data from 3661 patients, achieves an area under the receiver operating characteristic curve (AUC) of 0.786 (95% CI: 0.745–0.830) when predicting deterioration within 96 hours. The deep neural network extracts informative areas of chest X-ray images to assist clinicians in interpreting the predictions and performs comparably to two radiologists in a reader study. In order to verify performance in a real clinical setting, we silently deployed a preliminary version of the deep neural network at New York University Langone Health during the first wave of the pandemic, which produced accurate predictions in real-time. In summary, our findings demonstrate the potential of the proposed system for assisting front-line physicians in the triage of COVID-19 patients.
Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization
Authors: Jørgensen Astrid S. , Daugvilaite Viktorija , De Filippo Katia , Berg Christian , Mavri Masa , Benned-Jensen Tau , Juzenaite Goda , Hjortø Gertrud , Rankin Sara , Våbenø Jon , Rosenkilde Mette M.
Published: May 2021

Following the FDA-approval of the hematopoietic stem cell (HSC) mobilizer plerixafor, orally available and potent CXCR4 antagonists were pursued. One such proposition was AMD11070, which was orally active and had superior antagonism in vitro; however, it did not appear as effective for HSC mobilization in vivo. Here we show that while AMD11070 acts as a full antagonist, plerixafor acts biased by stimulating β-arrestin recruitment while fully antagonizing G protein. Consequently, while AMD11070 prevents the constitutive receptor internalization, plerixafor allows it and thereby decreases receptor expression. These findings are confirmed by the successful transfer of both ligands’ binding sites and action to the related CXCR3 receptor. In vivo, plerixafor exhibits superior HSC mobilization associated with a dramatic reversal of the CXCL12 gradient across the bone marrow endothelium, which is not seen for AMD11070. We propose that the biased action of plerixafor is central for its superior therapeutic effect in HSC mobilization.
A modular two yeast species secretion system for the production and preparative application of unspecific peroxygenases
Authors: Püllmann Pascal , Knorrscheidt Anja , Münch Judith , Palme Paul R. , Hoehenwarter Wolfgang , Marillonnet Sylvestre , Alcalde Miguel , Westermann Bernhard , Weissenborn Martin J.
Published: May 2021

Fungal unspecific peroxygenases (UPOs) represent an enzyme class catalysing versatile oxyfunctionalisation reactions on a broad substrate scope. They are occurring as secreted, glycosylated proteins bearing a haem-thiolate active site and rely on hydrogen peroxide as the oxygen source. However, their heterologous production in a fast-growing organism suitable for high throughput screening has only succeeded once—enabled by an intensive directed evolution campaign. We developed and applied a modular Golden Gate-based secretion system, allowing the first production of four active UPOs in yeast, their one-step purification and application in an enantioselective conversion on a preparative scale. The Golden Gate setup was designed to be universally applicable and consists of the three module types: i) signal peptides for secretion, ii) UPO genes, and iii) protein tags for purification and split-GFP detection. The modular episomal system is suitable for use in Saccharomyces cerevisiae and was transferred to episomal and chromosomally integrated expression cassettes in Pichia pastoris. Shake flask productions in Pichia pastoris yielded up to 24 mg/L secreted UPO enzyme, which was employed for the preparative scale conversion of a phenethylamine derivative reaching 98.6 % ee. Our results demonstrate a rapid, modular yeast secretion workflow of UPOs yielding preparative scale enantioselective biotransformations.
Efficient and gentle delivery of molecules into cells with different elasticity via Progressive Mechanoporation
Authors: Uvizl Alena , Goswami Ruchi , Gandhi Shanil Durgeshkumar , Augsburg Martina , Buchholz Frank , Guck Jochen , Mansfeld Jörg , Girardo Salvatore
Published: May 2021

Progressive Mechanoporation, a novel mechanoporation method that improves the delivery efficiency of molecules into cells of different elasticity via a multistage cell deformation controlled by a PDMS-based microfluidic platform.
Novel micron-thick brick cladding of polyfluorosilicone acrylates, a case study of conservation of historic brick wall in Hongcun village
Authors: Hao Jian , Yu Liyan , Cui Yongmei , Wan Wen , Huang Junyi
Published: May 2021

The cladding made from the polyfluorosilicone acrylate resin provided a covering of the microstructure of the shallow surface layer of old bricks, which makes the treated brick wall waterproof, moisture-proof, mildew-proof and weather resistant.
Selective-sampling Raman imaging techniques for ex vivo assessment of surgical margins in cancer surgery
Authors: Lizio Maria Giovanna , Boitor Radu , Notingher Ioan
Published: May 2021

Selective-sampling Raman Imaging enables intraoperative assessment of excised surgical margins in cancer surgery, a review.
Lithium doped nickel oxide nanocrystals with a tuned electronic structure for oxygen evolution reaction
Authors: Xiao Ziyi , Zhou Wei , Zhang Ning , Liao Chengan , Huang Shicheng , Chen Guoxin , Chen Gen , Liu Min , Liu Xiaohe , Ma Renzhi
Published: May 2021

The electronic structure of NiO nanocrystals is modified by doping with a small amount of Li+, and they show much enhanced OER activity in comparison with pure NiO and previously reported LiNiO2.
Efficient three-phase electrocatalytic CO2 reduction to formate on superhydrophobic Bi–C interfaces
Authors: Jiang Yifan , Zhang Xiaodong , Xu Dafu , Li Wenzhang , Liu Min , Qiu Xiaoqing
Published: May 2021

The gaseous layer occurred between the electrolyte and Bi–C catalysts can effectively reduce the influence of H2O molecules and promote the efficient access of high concentration CO2 to the surfaces of Bi nanospheres during the ECR process.
Insight into amoxicillin sodium heterosolvates and non-solvated form: crystal structures, phase transformation behaviors, and desolvation mechanism
Authors: Cui Pingping , Yin Qiuxiang , Zhang Shihao , Yang Wenchao , Jia Lihong , Dai Jiayu , Zhou Ling , Wang Zhao
Published: May 2021

Methanol and methyl acetate molecules played different roles in the formation of SM–M amoxicillin sodium heterosolvate. A two-step desolvation mechanism of novel heterosolvates was proposed.
First-principles investigation of CO and CO2 adsorption on pristine and Fe-doped planar carbon allotrope net-Y
Authors: Li Bai , Shao Zhi-Gang , Feng Yu-Tao
Published: May 2021

Net-Y was firstly used to study the adsorption of CO and CO2. The introduction of Fe atom can significantly enhance the adsorption strength and changes the system from physisorption to chemisorption. And the adsorption stability is much better than that for traditional 2D materials.
Quantification of particulate Ag in rainbow trout organs following dietary exposure to silver nitrate, or two forms of engineered silver nanoparticles
Authors: Clark Nathaniel J. , Clough Robert , Boyle David , Handy Richard D.
Published: May 2021

Following exposure to a diet containing a control (no added Ag), AgNO3, Ag NPs or Ag2S NPs, Ag-containing particles were found in organs of all treatments, with the highest concentrations following exposure to AgNO3 or Ag NP.
2D nanosheet enabled thin film nanocomposite membranes for freshwater production – a review
Authors: Mallya Deepak Surendhra , Dumée Ludovic F. , Muthukumaran Shobha , Lei Weiwei , Baskaran Kanagaratnam
Published: May 2021

This review presents state-of-the-art progress in 2D-enabled TFN membranes for RO and NF applications in water treatment with emphasis on impact of 2D nanosheet on membrane properties, performance, and its associated challenges.
Recent advances of Ritter reaction and its synthetic applications
Authors: Chen Meng-En , Chen Xiao-Wei , Hu Yue-Hong , Ye Rui , Lv Jian-Wei , Li Baosheng , Zhang Fu-Min
Published: May 2021

This review provides a comprehensive survey of Ritter reactions from 2014 to 2020.
Samarium(iii) catalyzed synthesis of alkenylboron compounds via hydroboration of alkynes
Authors: Liu Jichao , Xie Yaoyao , Wu Caiyan , Shao Yinlin , Zhang Fangjun , Shi Yinyin , Liu Qianrui , Chen Jiuxi
Published: May 2021

The homoleptic lanthanide complex Sm[N(TMS)2]3 is an efficient rare-earth catalyst for the hydroboration of alkynes to the corresponding alkenylboron compounds.
Exploring synthetic and therapeutic prospects of new thiazoline derivatives as aldose reductase (ALR2) inhibitors
Authors: Shehzad Muhammad Tariq , Imran Aqeel , Hameed Abdul , Rashida Mariya al , Bibi Marium , Uroos Maliha , Asari Asnuzilawati , Iftikhar Shafia , Mohamad Habsah , Tahir Muhammad Nawaz , Shafiq Zahid , Iqbal Jamshed
Published: May 2021

Inhibition of aldose reductase (ALR2) by using small heterocyclic compounds provides a viable approach for the development of new antidiabetic agents.
Atmospheric pressure plasma liquid assisted deposition of polydopamine/acrylate copolymer on zirconia (Y-TZP) ceramics: a biocompatible and adherent nanofilm
Authors: Hodásová Ľudmila , Quintana Robert , Czuba Urszula , del Valle Luis J. , Fargas Gemma , Alemán Carlos , Armelin Elaine
Published: May 2021

Polydopamine–ethylene glycol dimethacrylate copolymer is a biocompatible coating with cell adhesion promotion and antibiofilm properties.
Correction: Exploration of the cofactor specificity of wild-type phosphite dehydrogenase and its mutant using molecular dynamics simulations
Authors: Liu Kunlu , Wang Min , Zhou Yubo , Wang Hongxiang , Liu Yudong , Han Lu , Han Weiwei
Published: May 2021

Correction for ‘Exploration of the cofactor specificity of wild-type phosphite dehydrogenase and its mutant using molecular dynamics simulations’ by Kunlu Liu et al., RSC Adv., 2021, 11, 14527–14533, DOI: 10.1039/D1RA00221J.
A proton/macromolecule-sensing approach distinguishes changes in biological membrane permeability during polymer/lipid-based nucleic acid delivery
Authors: Boonstra Eger , Hatano Hiroaki , Miyahara Yuji , Uchida Satoshi , Goda Tatsuro , Cabral Horacio
Published: May 2021

Using a proton-sensing transistor, changes in membrane permeability induced by transfection reagents were assessed, shedding light on endosomal escape mechanisms.
Design and fabrication of a flexible glucose sensing platform toward rapid battery-free detection of hyperglycaemia
Authors: Fujita Hajime , Yamagishi Kento , Zhou Wenshen , Tahara Yu , Huang Shao Ying , Hashimoto Michinao , Fujie Toshinori
Published: May 2021

The rapid detection of postprandial hyperglycaemia is imperative for the diagnosis of diabetes and the assessment of health risks for nondiabetics.